Preliminary Estimates Of Efficacy Research Articles

Phase I Clinical Trial of High Doses of Seleno-L-methionine in Combination with Axitinib in Patients with Previously Treated Metastatic Clear Cell Renal Cell Carcinoma.

Data in clear cell renal cell carcinoma (ccRCC) xenografts defined the seleno-L-methionine (SLM) dose and the plasma selenium concentrations associated with the enhancement of HIF1α/2α degradation, stabilization of tumor vasculature, enhanced drug delivery, and efficacy of axitinib. The data provided the rationale for the development of this phase I clinical trial of SLM and axitinib in advanced or metastatic relapsed ccRCC. Patients were ≥18 years with histologically and radiologically confirmed advanced or metastatic ccRCC who had received at least one prior systemic therapy, which could include axitinib (last dose ≥6 months prior to enrollment). Escalating dose levels of SLM (2500, 3000 and 4000 μg) were administered orally twice daily for 14 days, then once daily concurrently with axitinib 5 mg twice daily using a 3+3 design in Phase I. Patients were treated at the 4000 μg dose level in the expansion cohort to obtain preliminary estimates of efficacy. No dose limiting toxicities occurred at the 4000 μg SLM dose level. Among the 27 patients treated with 4000 μg of SLM, the overall response rate was 55.6%, median duration of response was 18.4 months, median progression-free survival was 14.8 months, and median overall survival was 19.6 months. Preliminary results have shown that plasma selenium concentrations, inhibition of TGF-β1 and stabilization of tumor vasculature by SLM are time dependent. SLM (4000 μg) in sequential combination with axitinib is well tolerated with encouraging efficacy.

Effect of cervical traction on cervicogenic headache in patients with cervical radiculopathy: a preliminary randomized controlled trial

BackgroundCervical radiculopathy (CR) is a common condition, often associated with cervicogenic headache (CGH), a secondary headache arising from cervical spine disorders. Mechanical intermittent cervical traction (MICT) is frequently prescribed to treat CR symptoms. The purpose of the study was to make a preliminary estimate of efficacy of adding MICT to conventional rehabilitation on CGH in patients with cervical radiculopathy.MethodsA total of 36 CR patients with CGH were randomly allocated to 3 equally sized groups (A, B and C). The treatment consisted of twelve sessions of conventional rehabilitation (4 weeks) combined with MICT (2 kg for group A, 8 kg for group B and 12 kg for group C). Primary outcomes were CGH intensity (visual analog scale) and frequency (days per week). Secondary outcomes were radicular pain intensity (visual analog scale), cervical range of motion (cervical range of motion instrument), proprioception (cervical range of motion instrument) and muscle strength (MicroFET2 dynamometer), handgrip strength (handheld dynamometer), function (Neck Disability Index), kinesiophobia (Tampa Scale for KInesiophobia), anxiety and depression (Hospital Anxiety and Depresion questionnaire), and quality of life (World Health Organization Quality of Life). Patients were assessed at baseline, one, three and six months after the beginning of treatment. The post hoc Dunn testing was used to determine which traction load had the better effect on CGH symptoms.ResultsAt one, three and six months follow-ups, Group C exhibited the highest improvement in CGH intensity and frequency compared to the other groups (p = 0.021 and p = 0.023; p = 0.012 and p = 0.01; p = 0.005 and p = 0.005). Both groups C and B showed a significant improvement in radicular pain compared to group A at one month follow-up (p = 0.05).The improvement in group C was significantly better in terms of function (p = 0.049) and anxiety (p = 0.011) at three months and quality of life at six months (Psychological p = 0.046 and Environment p = 0.006).ConclusionsThe blend of conventional rehabilitation alongside 12 kg MICT seems to be efficacious in diminishing both the intensity and frequency of CGH in patients with CR. These advantages appear to last for up to six months following the treatment period, potentially leading to decreased CGH severity and occurrence rates, heightened functionality, reduced anxiety levels, and an overall enhancement in quality of life. These findings are preliminary and require confirmation in larger trials.Trial registrationThe study protocol was retrospectively registered at the Pan African Clinical Trial Registry (PACTR202401838955948). Date of registration is 16/01/2024.

Prevention of postpartum methamphetamine use with micronized progesterone trial (PROMPT): A pilot randomized controlled trial protocol

While most pregnant individuals with methamphetamine use disorder (MUD) achieve abstinence, the postpartum period remains a vulnerable time for return to methamphetamine use (MU). Promising data from human and animal models, including three randomized controlled trials, suggest that micronized progesterone may prevent postpartum return to cocaine and nicotine use by reducing cravings. The primary objective of this study is to assess feasibility of enrollment and randomization of postpartum individuals with MUD to micronized progesterone to prevent return to MU. The secondary objectives are to evaluate safety, establish a preliminary estimate of efficacy, and characterize the association between allopregnanolone levels and methamphetamine cravings. This is a pilot double-blind placebo randomized controlled trial. We plan to enroll 40 postpartum individuals with MUD over 24-months. Individuals, stratified by opioid use disorder (OUD), are randomized 1:1-400mg oral micronized progesterone daily or placebo and attend weekly study sessions for 12 weeks. Feasibility is measured by achieving 80% of enrollment goal. Safety is evaluated by side effect frequency, mental health status changes, lactation and medical complications. Efficacy is assessed by comparing proportion of participants with return to MU and time to return to MU based on self-report or urine testing between treatment and control groups. Salivary allopregnanolone levels and methamphetamine cravings are compared between the groups. Study results will provide a first critical step towards potential intervention for prevention of return to MU among postpartum individuals. Completion of this trial will set the stage for a large-scale efficacy trial.

Creating a digital approach for promoting physical activity in pediatric pulmonary hypertension: A framework for future interventions.

Children with pulmonary hypertension (PH) often demonstrate limited exercise capacity. Data support exercise as an effective nonpharmacologic intervention among adults with PH. However, data on exercise training in children and adolescents are limited, and characteristics of the optimal exercise program in pediatric PH have not been identified. Exercise programs may have multiple targets, including muscle deficits which are associated with exercise limitations in both adult and pediatric PH. Wearable accelerometer sensors measure physical activity volume and intensity in the naturalistic setting and can facilitate near continuous data transfer and bidirectional communication between patients and the study team when paired with informatics tools during exercise interventions. To address the knowledge gaps in exercise training in pediatric PH, we designed a prospective, single arm, nonrandomized pilot study to determine feasibility and preliminary estimates of efficacy of a 16-week home exercise intervention, targeting lower extremity muscle mass and enriched by wearable mobile health technology. The exercIse Training in pulmONary hypertEnsion (iTONE) trial includes (1) semistructured exercise prescriptions tailored to the participant's baseline level of activity and access to resources; (2) interval goal setting fostering self-efficacy; (3) real time monitoring of activity via wearable devices; (4) a digital platform enabling communication and feedback between participant and study team; (5) multiple avenues to assess participant safety. This pilot intervention will provide information on the digital infrastructure needed to conduct home-based exercise interventions in PH and will generate important preliminary data on the effect of exercise interventions in youth with chronic cardiorespiratory conditions to power larger studies in the future.

ICare – a self-directed, interactive online program to improve health and wellbeing for people living with upper gastrointestinal or hepato-pancreato-biliary cancers, and their informal carers: the study protocol for a Phase II randomised controlled trial

BackgroundUp to 70% of people diagnosed with upper gastrointestinal (GI) tract or hepato-pancreato-biliary (HPB) cancers experience substantial reductions in quality of life (QoL), including high distress levels, pain, fatigue, sleep disturbances, weight loss and difficulty swallowing. With few advocacy groups and support systems for adults with upper GI or HPB cancers (i.e. pancreas, liver, stomach, bile duct and oesophageal) and their carers, online supportive care programs may represent an alternate cost-effective mechanism to support this patient group and carers. iCare is a self-directed, interactive, online program that provides information, resources, and psychological packages to patients and their carers from the treatment phase of their condition. The inception and development of iCare has been driven by consumers, advocacy groups, government and health professionals. The aims of this study are to determine the feasibility and acceptability of iCare, examine preliminary efficacy on health-related QoL and carer burden at 3- and 6-months post enrolment, and the potential cost-effectiveness of iCare, from health and societal perspectives, for both patients and carers.Methods and analysisA Phase II randomised controlled trial. Overall, 162 people with newly diagnosed upper GI or HPB cancers and 162 carers will be recruited via the Upper GI Cancer Registry, online advertisements, or hospital clinics. Patients and carers will be randomly allocated (1:1) to the iCare program or usual care. Participant assessments will be at enrolment, 3- and 6-months later. The primary outcomes are i) feasibility, measured by eligibility, recruitment, response and attrition rates, and ii) acceptability, measured by engagement with iCare (frequency of logins, time spent using iCare, and use of features over the intervention period). Secondary outcomes are patient changes in QoL and unmet needs, and carer burden, unmet needs and QoL. Linear mixed models will be fitted to obtain preliminary estimates of efficacy and variability for secondary outcomes. The economic analysis will include a cost-consequences analysis where all outcomes will be compared with costs.DiscussioniCare provides a potential model of supportive care to improve QoL, unmet needs and burden of disease among people living with upper GI or HPB cancers and their carers.Australian and New Zealand Clinical Trials RegistryACTRN12623001185651. This protocol reflects Version #1 26 April 2023.

Internet-based psychoeducation and support programme for relatives of young people with early psychosis: results of the first German-language intervention.

International clinical guidelines recommend Family Interventions (FIs) especially for families of people at early stages of psychosis. The German S3 treatment guideline for schizophrenia gives FIs the highest level of clinical recommendation. However, some family relatives have limited access to these services due to health system constrains. Digital interventions have emerged as a solution to overcome this hindered access to evidence-based family interventions. The present pilot study evaluates the feasibility and potential efficacy of the first German moderated online psychoeducation and support programme (ePSP) for relatives of people with early psychosis, with the additional purpose to improve accessibility and reduce waiting times. A pre-post study was performed. A brief recruitment period was pre-established (10 weeks) to test potential improvement of regular therapy waiting times in Germany. A total of 25 relatives of people with early psychosis were recruited and received the 12-week moderated online intervention. Assessments were conducted at baseline and at post intervention. Acceptance of the intervention and the user's experience were also evaluated at post intervention. Recruitment, retention rates and qualitative data support the feasibility and acceptability of the ePSP. Significant positive effects of the interventions were found on key therapeutic targets, including both primary outcomes (i.e., perceived stress and beliefs about the illness). Twenty-one participants also completed the open-ended questions of the user experience questionnaire, which yielded three main themes: most important modules, difficulties in using the programme and ways to improve ePSP. These results provide preliminary efficacy estimates for a fully powered RCT to investigate superiority (or equipoise) effects of the ePSP in comparison to the routine face-to-face family therapy groups. This future RCT will also allow further exploration of ePSP to improve access to psychological therapy for relatives of young people with psychosis, also in relation to the new ground-breaking Digital Healthcare Act in Germany.

Abstract P042: Phase I/II first-in-human study of TT-10 (A2AB inhibitor) as a single agent in subjects with advanced selected solid tumors

Abstract Immunotherapy has emerged as a potent tool for cancer treatment by activating the immune system to recognize and attack cancer cells. Immune checkpoint blockage has shown notable clinical success in several malignancies such as advanced non-small cell lung cancer, melanoma, advanced kidney cancer and several other indications, as demonstrated with the approval of CTLA-4 and PD-1/PD-L1 checkpoint inhibitors. However, the efficacy of checkpoint inhibitors to date is limited to only a subset of patients, even within the same cancer type. Thus, the continued focus in the cancer immunotherapy field is to identify new immunosuppressive pathways that allow cancer cells to evade immune surveillance. One emerging pathway of interest is the purinergic pathway, in which adenosine is recognized as a key metabolic checkpoint, and high levels of extracellular adenosine have been evidenced to mediate profound tumor resistance. In this first-in-human Phase I/II study, we explore selective inhibition of the adenosine A2A receptor (A2AR) with TT-10, an oral immune-oncology agent, as a treatment option for subjects with select solid tumors. TT-10 is being evaluated as a single agent, in an open-label, non-randomized, multicenter, dose-escalation (phase 1) and dose-expansion (phase 2) study in subjects with renal cell cancer (RCC), castrate resistant prostate cancer (CRPC) and non-small cell lung cancer (NSCLC) (NCT# NCT04969315). Phase 1 (Cohort A) will explore ascending doses of TT-10, taken orally (10, 20, 50, 100, 200 mg, BID), utilizing a 3+3 design in 28-day cycles to identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (R2PD). Enrollment will be open to all three indications. Phase 2 will begin once RP2D is determined and will enroll up to 60 subjects, with approximately 15 subjects per cohort (B.) RCC, (C.) CRPC, (D.) NSCLC (E.) Exploratory Tumor Biopsy). The primary objectives of this study are to evaluate the safety, tolerability, and MTD or the RP2D of TT-10 monotherapy. Secondary objectives are to obtain a preliminary estimate of efficacy, evaluate PK and anti-tumor activity of TT-10 monotherapy, with exploratory objectives inclusive of identification of candidate biomarkers and biomarkers that might predict response, as well as, exploring if adenosine signature and/or receptor expression in tumor tissue at baseline might predict response. Subjects must have locally advanced, recurrent or metastatic neoplastic disease that is not curable by currently available, failure to respond to standard therapy or for whom no appropriate therapies are available, and have a life expectancy of ≥ 3 months to be eligible for the trail. Select subjects that would like to participate in Cohort E.) Exploratory Tumor Biopsy must have an accessible tumor for pre and post dose biopsies. Enrollment of phase 1 is expected to start October 2021. Citation Format: Sushant Kumar, Kasim Mookhtiar, Desa Rae Pastore, Brian Schwartz, Vijay Reddy. Phase I/II first-in-human study of TT-10 (A2AB inhibitor) as a single agent in subjects with advanced selected solid tumors [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P042.

The Reward Re-Training protocol: A novel intervention approach designed to alter the reward imbalance contributing to binge eating during COVID-19.

Reduced exposure to social reward during the COVID‐19 pandemic may result in both reduced reward response to day‐to‐day life activities and elevated reward response to substances or naturally rewarding stimuli (e.g., food). The combined hypo‐ and hyper‐reward responses results in a reward imbalance, which has been noted as a relevant maintenance factor for eating disorders (EDs) characterized by binge eating. This registered report describes the protocol for a pilot randomized controlled trial (RCT) comparing supportive therapy to a novel treatment targeting reward imbalance (Reward Re‐Training; RRT) for individuals with binge eating. Aims of the current study include to confirm feasibility and acceptability of RRT, to evaluate the ability of RRT to engage critical targets, and to provide preliminary estimates of efficacy in reducing ED symptoms at both posttreatment and 3‐month follow‐up.Sixty participants will be randomized to either RRT or supportive therapy. For both conditions, treatment will be delivered in 10 weekly group outpatient therapy sessions conducted remotely using videoconferencing software. Assessments will be conducted at baseline, mid‐treatment, posttreatment, and 3‐month follow‐up to measure feasibility, acceptability, critical treatment targets (i.e., reward to day‐to‐day life activities, reward to palatable foods, social isolation, and loneliness), and ED symptoms.

Work2Prevent, an Employment Intervention Program as HIV Prevention for Young Men Who Have Sex With Men and Transgender Youth of Color (Phase 3): Protocol for a Single-Arm Community-Based Trial to Assess Feasibility and Acceptability in a Real-World Setting.

BackgroundIn the United States, young cisgender men who have sex with men (YMSM), young transgender women (YTW), and gender nonconforming (GNC) youth face elevated rates of HIV infection. However, racial and ethnic disparities in adolescent HIV infection cannot be attributed to individual-level factors alone and are situated within larger social and structural contexts that marginalize and predispose sexual and gender minority youth of color to HIV. Addressing broader ecological factors that drive transmission requires interventions that focus on the distal drivers of HIV infection, including violence exposure, housing, food insecurity, educational attainment, and employment. Given the ways that economic instability may make YMSM, YTW, and GNC youth of color vulnerable to HIV exposure, this study focuses on employment as an HIV prevention intervention. More specifically, the intervention, called Work2Prevent (W2P), targets economic stability through job readiness and employment as a means of preventing behaviors and factors associated with adolescent and young adult HIV, such as transactional sex work and homelessness. The intervention was adapted from iFOUR, an evidence-based employment program for HIV-positive adults in phase 1 of this study, and pilot tested in a university-based setting in phase 2.ObjectiveThis paper aims to describe the protocol for the community-based test phase of W2P. The purpose of this phase was to pilot test a tailored, theoretically informed employment intervention program among YMSM, YTW, and GNC youth of color within a lesbian, gay, bisexual, transgender, and queer (LGBTQ) community setting.MethodsThe employment intervention was pilot tested using a single-arm pretest-posttest trial design implemented among a sample of vulnerable YMSM, YTW, and GNC youth of color using services within a community-based LGBTQ center. Assessments will examine intervention feasibility, acceptability, and preliminary estimates of efficacy.ResultsPhase 3 of W2P research activities began in May 2019 and was completed in December 2019. Overall, 41 participants were enrolled in the community-based pilot.ConclusionsThis study will assess intervention feasibility and acceptability in the target populations and determine preliminary efficacy of the intervention to increase employment and reduce vulnerability to HIV when implemented in a community-based setting serving LGBTQ youth of color. Testing the intervention in a community setting is an opportunity to evaluate how recruitment, retention, and other outcomes are impacted by delivery in a venue akin to where this intervention could eventually be used by nonresearchers. If W2P demonstrates feasibility and acceptability, a larger multisite trial implemented in multiple community settings serving YMSM, YTW, and GNC youth of color is planned.Trial RegistrationClinicalTrials.gov NCT03313310; https://clinicaltrials.gov/ct2/show/NCT03313310International Registered Report Identifier (IRRID)DERR1-10.2196/18051

An Employment Intervention Program (Work2Prevent) for Young Men Who Have Sex With Men and Transgender Youth of Color (Phase 2): Protocol for a Single-Arm Mixed Methods Pilot Test to Assess Feasibility and Acceptability.

BackgroundYoung cisgender men who have sex with men (YMSM), young transgender women (YTW), and gender nonconforming (GNC) youth of color face substantial economic and health disparities. In particular, HIV risk and infection among these groups remains a significant public health issue. In 2017, 17% of all new HIV diagnoses were attributed to male-to-male sexual contact among adolescents and young adults aged 13 to 24 years. However, such disparities cannot be attributed to individual-level factors alone but rather are situated within larger social and structural contexts that marginalize and predispose YMSM, YTW, and GNC youth of color to increased HIV exposure. Addressing social and structural risk factors requires intervention on distal drivers of HIV risk, including employment and economic stability. The Work2Prevent (W2P) study aims to target economic stability through job readiness and employment as a structural-level intervention for preventing adolescent and young adult HIV among black and Latinx YMSM, YTW, and GNC youth. This study seeks to assess intervention feasibility and acceptability in the target populations and determine preliminary efficacy of the intervention to increase employment and reduce sexual risk behaviors.ObjectiveThe goal of the research is to pilot-test a tailored, theoretically informed employment intervention program among YMSM, YTW, and GNC youth of color. This intervention was adapted from Increased Individual Income and Independence, an existing evidence-based employment program for HIV-positive adults during phase 1 of the W2P study.MethodsThe employment intervention will be pilot-tested among vulnerable YMSM, YTW, and GNC youth of color in a single-arm pre-post trial to assess feasibility, acceptability, and preliminary estimates of efficacy.ResultsResearch activities began in March 2018 and were completed in November 2019. Overall, 5 participants were enrolled in the pretest and 51 participants were enrolled in the pilot.ConclusionsInterventions that address the social and structural drivers of HIV exposure and infection are sorely needed in order to successfully bend the curve in the adolescent and young adult HIV epidemic. Employment as prevention has the potential to be a scalable intervention that can be deployed among this group.Trial RegistrationClinicalTrials.gov NCT03313310; https://clinicaltrials.gov/ct2/show/NCT03313310International Registered Report Identifier (IRRID)DERR1-10.2196/16401

Abstract A081: Trial Library: A pilot study to examine feasibility, acceptability, and preliminary estimates of efficacy for an online clinical trial matching website on patient-prompted conversations for prostate cancer clinical trials

Abstract Background: The ability of clinical trials to effectively translate into therapeutic interventions for the general population can be limited by a lack of representative participants in these trials. There is an acute need to develop informational resources regarding cancer clinical trials that meet the linguistic and literary needs of under-represented and vulnerable populations. Current practices utilize a one-size-fits-all approach that may be inaccessible to a diverse audience. Given the increased utilization of online resources for health information among a diverse patient population and across age groups, we developed a website, called Trial Library, which may serve as a prostate cancer clinical trial matching tool. We hypothesize that use of the Internet-based clinical trial matching tool in clinic will increase the number of patient-initiated conversations with physicians about clinical trial options, and by extension, improve enrollment to therapeutic cancer clinical trials among a diverse participant pool. Procedures/Design/Aims: This is a nonrandomized, nontherapeutic interventional pilot study. The study will be performed in genitourinary medical oncology clinic at UCSF Helen Diller Family Comprehensive Cancer Center. We will measure the feasibility and acceptability of a clinical trial matching tool that includes two unique features: user-validated clinical trial content and navigation schema. We will measure preliminary estimates of efficacy of the online clinical trial matching tool in triggering patient-promoted conversations regarding clinical trials and ultimately clinical trial enrollment. Discussion: Trial Library is designed to be an accessible informational resource for patients from diverse levels of health literacy and English proficiency. This pilot study will provide important preliminary results to inform the design of the website and subsequent testing outside of clinic. Additionally, this website will ultimately serve as a model for clinical trial information that can be translated across tumor types. Note: This abstract was not presented at the conference. Citation Format: Hala T. Borno, Brian Bakke, Anke Hebig Prophet, Yoon-Ji Kim, Jan Yaeger, Jessica Chao, Pelin Cinar, Celia Kaplan, Eric Small, Christy Boscardin, Ralph Gonzales. Trial Library: A pilot study to examine feasibility, acceptability, and preliminary estimates of efficacy for an online clinical trial matching website on patient-prompted conversations for prostate cancer clinical trials [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A081.

A randomized phase II trial of secondary cytoreductive surgery (SCS) +/- carboplatin hyperthermic intraperitoneal chemotherapy (HIPEC) in patients (pts) with recurrent platinum-sensitive ovarian cancer (EOC).

6016 Background: The role of HIPEC for recurrent EOC is not well defined. The aim of this phase II study was to determine the proportion of pts without evidence of disease progression at 24 months post SCS +/- intraoperative carboplatin HIPEC. Methods: After SCS to ≤ 0.5 cm residual visible disease pts were intraoperatively randomized to carboplatin HIPEC (800mg/m2 for 90 minutes) or no HIPEC. The HIPEC arm received 5 additional and the standard arm received 6 postoperative cycles of IV platinum-based chemotherapy without maintenance treatment. Based on an exact binomial single stage “pick the winner” design, each arm is considered “winner” if ≥ 17/49 pts are without evidence of disease progression at 24 months post SCS. Secondary objectives include postoperative grade ≥ 3 toxicity and complications within 4 weeks post SCS, and pharmacokinetics of carboplatin HIPEC. Results: Of 98 pts, 49 (50%) were randomized to the HIPEC arm. The arms were well balanced for age, stage, histology, BRCA mutation status, prior chemotherapy, and disease-free interval. Complete gross SCS was achieved in 94% of the standard and 82% of the HIPEC arm (p = 0.12). Bowel resection was performed more frequently in the standard (65%) compared to the HIPEC arm (37%; p = 0.008). Median operative time was shorter in the standard (296 minutes) compared to the HIPEC arm (475 minutes; p < 0.001). There was no perioperative mortality and no difference in use of ostomies, length of stay or postoperative toxicity. At a median follow-up of 27.7 months (range: 8.8-81.8 months) 70 of 98 pts progressed and 26 died with a median progression free survival (PFS) of 14.3 months (12.1-16 months) and a median overall survival (OS) of 55.2 months (47.7-not reached). At 24 months post SCS 32 pts progressed within 24 months in the standard versus 35 in the HIPEC arm. There was no statistically significant difference in median PFS (15.4 vs 12.3 months, p = 0.173) or median OS (69.2 vs 53.1 months, p = 0.317) between arms. These are preliminary efficacy estimates as 83/98 pts have a minimum of 24 months follow-up. Conclusions: The HIPEC arm did not reach the predefined “winner” endpoint; the standard arm is still undetermined as 6 pts did not reach 24 months follow-up. No perioperative mortality, and no increased perioperative morbidity or toxicity was seen with HIPEC. SCS with carboplatin HIPEC followed by 5 cycles of platinum-based chemotherapy was not superior to SCS without HIPEC followed by 6 cycles of platinum-based chemotherapy. Clinical trial information: NCT01767675.

P517 A randomised, placebo-controlled pilot trial of faecal microbiota transplantation for paediatric Crohn’s disease

Abstract Background The role of faecal microbiota transplant (FMT) in Crohn’s disease (CD) remains unclear. Small, open-label case series have shown high rates of clinical remission but protocols have varied across studies, and no randomised controlled trials (RCT) have been performed. We present a protocol for the first pilot RCT of FMT in paediatric CD patients, using a novel colonoscopic + oral capsular intervention that uses fresh-frozen and prepared, lyophilised donor stool. We will measure improvements in clinical disease activity, inflammatory biomarkers, endoscopic markers of mucosal inflammation, as well as, assess key aspects of trial feasibility. Methods Patients 3–17 years with active CD, on stable medication doses for 4 weeks are eligible. Patients will have an initial colonoscopy during which they will receive an infusion into the terminal ileum of normal saline (placebo) or prepared healthy donor stool (RBX2660; Rebiotix, USA) (active). This will be followed by 6-weeks of bi-weekly oral capsular therapy, containing methylcellulose (placebo) or lyophilised healthy adult donor stool (RBX7455; Rebiotix, USA). Randomisation is 2:1 to active and placebo arms (n = 45). Patients will be followed over 24 weeks. (Figure 1) Results Study feasibility will be assessed by: rate of recruitment, completion of sample collections, and frequency and type of adverse events. Clinical outcomes will be measured serially using: Paediatric Crohn’s Disease Activity Index (PCDAI), faecal calprotectin, blood inflammatory markers, and Simple Endoscopic Score for Crohn’s Disease (SES-CD) at baseline and end-of-study. Stool 16s rRNA, metagenomics, and urine metabolomics profiles will be performed on collected stool and urine samples. Patients who complete the placebo arm will be eligible to enter an open-label extension study. Results will be measured through ITT and PP analyses. Proportions and percentages will be reported on feasibility outcomes; odds ratios, mean differences and 95% confidence intervals will be reported on clinical outcomes as preliminary estimates of efficacy. Conclusion This is the first pilot RCT of FMT in the treatment of CD. Recruitment commenced April 2019 and 13 patients have met screening criteria, with 5 enrolled thus far. This study is novel for its focus on paediatric CD patients, and its use of a combined oral + colonoscopic FMT delivery method. The results of this trial will offer preliminary estimates of efficacy for FMT-based therapies in CD, and may support expansion to a future larger multicenter paediatric RCT using our validated study protocol.

Assessing the acceptability and efficacy of teens taking charge: Transplant-A pilot randomized control trial.

Adolescents who have undergone SOT are at heightened risk for graft failure. This pilot randomized controlled trial aimed to determine the feasibility and obtain preliminary estimates of efficacy of the online TTC program. TTC is a web-based self-management program for adolescent SOT patients. Participants-kidney or liver transplant candidates or recipients-were enrolled over a 2-year period and randomized to either an intervention group that accessed TTC or a control group that did not access the program. Outcome measures included feasibility, how much the program was utilized, and pre- and post-intervention health-related outcomes evaluating self-management, self-efficacy, mood, use of healthcare services, and knowledge. Semi-structured interviews were conducted with participants post-intervention. Forty-two participants were enrolled in the study. Participants in the intervention group expressed that they enjoyed learning about other teens' experiences, but reported barriers to accessing the site, such as being too busy, computer being too slow, and not being able to access the site on their mobile device. Time spent using the website was low for the majority of participants. Patients less than 1-year post-transplant accessed TTC more than patients who had their transplant for longer. No significant differences were found for health-related outcomes between groups. No differences in health-related outcomes were found between groups. Further studies that examine barriers to engagement with web-based education tools are warranted.

A step towards equitable clinical trial recruitment: a protocol for the development and preliminary testing of an online prostate cancer health information and clinical trial matching tool

BackgroundRecruitment of a diverse participant pool to cancer clinical trials is an essential component of clinical research as it improves the generalizability of findings. Investigating and piloting novel recruitment strategies that take advantage of ubiquitous digital technologies has become an important component of facilitating broad recruitment and addressing inequities in clinical trial participation. Equitable and inclusive recruitment improves generalizability of clinical trial outcomes, benefiting patients, clinicians, and the research community. The increasing prevalence of online connectivity in the USA and use of the Internet as a resource for medical information provides an opportunity for digital recruitment strategies in cancer clinical trials. This study aims to measure the acceptability, preliminary estimates of efficacy, and feasibility of the Trial Library intervention, an Internet-based cancer clinical trial matching tool. This study will also examine the extent to which the Trial Library website, designed to address the linguistic and literacy needs of broader patient populations, influences patient-initiated conversations with physicians about clinical trial participation.MethodsThis is a study protocol for a non-randomized, single-arm pilot study. This is a mixed methods study design that utilizes the statistical analysis of quantitative survey data and the qualitative analysis of interview data to assess the participant experience with the Trial Library intervention. This study will examine (1) acceptability as a measure of participant satisfaction with this intervention, (2) preliminary measure of efficacy as a measure of proportion of participants with documented clinical trial discussion in the electronic medical record, and (3) feasibility of the intervention as a measure of duration of clinical visit.DiscussionThe principles that informed the design of the Trial Library intervention aim to be generalizable to clinical trials across many disease contexts. From the ground up, this intervention is built to be inclusive of the linguistic, literacy, and technological needs of underrepresented patient populations. This study will collect essential preliminary data prior to a multi-site randomized clinical trial of the Trial Library intervention.Trial registrationThis study has received institutional approval from the Committee of Human Subjects Research at the University of California, San Francisco.

Augmented reality-based dance intervention for individuals with Parkinson’s disease: A pilot study

BackgroundThe effects of dance on improving the symptoms of individuals with Parkinson’s disease (PD) is well documented. Augmented reality devices, such as Google Glass, may be used to implement dance interventions to improve mobility and balance. ObjectiveTo evaluate the feasibility, safety, and acceptability of a mobile dance intervention and obtain preliminary efficacy estimates for assessment of the research protocol. MethodsSeven participants with PD were asked to use Google Glass preloaded with Moving Through Dance modules for three weeks. Changes in motor functions (balance, mobility) and non-motor functions (mood, quality of life) were evaluated before and after completion of the intervention. ResultsRecruitment rate was 50%, retention rate was 100%, and adherence to usage was 95%. The intervention was safe and accepted by participants. Use of Moving Through Glass improved mobility with a cognitive load (F(1, 5) = 10.76; p < 0.05). However, there were no significant changes to the participants’ balance scores, quality of life or mood. ConclusionsThe outcomes of this pilot study suggest that Moving Through Glass, as a mobile dance intervention, may be a safe way to increase physical activity through dance in individuals with PD. Its efficacy should be investigated in a properly powered randomized controlled trial.

Transcranial direct current stimulation (tDCS) for depression in pregnancy: A pilot randomized controlled trial

BackgroundDepression in pregnancy negatively affects maternal-child health. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation treatment for depression, has not been evaluated in pregnancy. ObjectiveTo conduct a pilot randomized controlled trial (RCT) to evaluate tDCS for antenatal depression. MethodsIn this pilot RCT in Toronto, Ontario (October 2014 to December 2016), adult pregnant women 14–32 weeks gestation with major depressive disorder who had declined antidepressant medication were considered for inclusion. Participants were randomly assigned 1:1 to tDCS or sham-control. Active tDCS comprised 30-min sessions of 2 mAmp direct current delivered over the dorsolateral prefrontal cortex, 5 days per week, for 3 weeks. Sham was administered similarly, but with current turned off after 30 s. Main outcomes were feasibility, acceptability, and protocol adherence. Maternal Montgomery Asperg Depression Rating Scale (MADRS) was measured post-treatment and at 4 and 12 weeks postpartum. ResultsOf 20 women randomized, 16 completed treatment and provided data (124 tDCS, 122 sham sessions). Views of treatment were positive with no serious adverse events. Post-treatment estimated marginal mean MADRS scores were 11.8 (standard error, SE 2.66) for tDCS and 15.4 (SE 2.51) for sham (p = 0.34). At 4 weeks postpartum, 75.0% of tDCS women were remitted versus 12.5% sham-control (p = 0.04). ConclusionsResults support proceeding to a definitive RCT to evaluate tDCS for antenatal depression. The preliminary efficacy estimates immediately post-treatment and in the postpartum, are encouraging with respect to the potential use of tDCS to improve treatment rates in this population. The trial was registered at: clinical trials.gov (NCT02116127).

A phase II randomized controlled trial of three exercise delivery methods in men with prostate cancer on androgen deprivation therapy

BackgroundExisting evidence demonstrates that 1:1 personal training (PT) improves many adverse effects of androgen deprivation therapy (ADT). Whether less resource-intensive exercise delivery models are as effective remains to be established. We determined the feasibility of conducting a multi-center non-inferiority randomized controlled trial comparing PT with supervised group (GROUP) and home-based (HOME) exercise programs, and obtained preliminary efficacy estimates for GROUP and HOME compared to PT on quality of life (QOL) and physical fitness.MethodsMen with prostate cancer on ADT were recruited from one of two experienced Canadian centres and randomized 1:1:1 to PT, GROUP, or HOME. Randomization was stratified by length of ADT use and site. Participants completed moderate intensity aerobic and resistance exercises 4–5 days per week for 6 months with a target 150 min per week of exercise. Exercise prescriptions were individualized and progressed throughout the trial. Feasibility endpoints included recruitment, retention, adherence, and participant satisfaction. The efficacy endpoints QOL, fatigue, and fitness (VO2 peak, grip strength, and timed chair stands) in GROUP and HOME were compared for non-inferiority to PT. Descriptive analyses were used for feasibility endpoints. Between-group differences for efficacy endpoints were examined using Bayesian linear mixed effects models.ResultsFifty-nine participants (mean age 69.9 years) were enrolled. The recruitment rate was 25.4% and recruitment was slower than projected. Retention was 71.2%. Exercise adherence as measured through attendance was high for supervised sessions but under 50% by self-report and accelerometry. Satisfaction was high and there was no difference in this measure between all three groups. Between-group differences (comparing both GROUP and HOME to PT) were smaller than the minimum clinically important difference on most measures of QOL, fatigue, and fitness. However, two of six outcomes for GROUP and four of six outcomes for HOME had a > 20% probability of being inferior for GROUP.ConclusionsFeasibility endpoints were generally met. Both GROUP and HOME interventions in men with PC on ADT appeared to be similar to PT for multiple efficacy outcomes, although conclusions are limited by a small sample size and cost considerations have not been incorporated. Efforts need to be targeted to improving recruitment and adherence. A larger trial is warranted.Trial registrationClinicalTrials.gov:NCT02046837. Date of registration: January 20, 2014.

A bilingual, Internet-based, targeted advertising campaign for prostate cancer clinical trials: Assessing the feasibility, acceptability, and efficacy of a novel recruitment strategy.

BackgroundTo address limitations in recruitment and enrollment of diverse, low-literacy patients into prostate cancer clinical trials, we evaluated the feasibility, acceptability, and efficacy of an English and Spanish, Internet-based, multilevel recruitment intervention.MethodsIntervention components included (1) a low-literacy, bilingual, automated, Internet-based clinical trial matching tool; (2) a bilingual nurse who assisted individuals with questions and enrollment; and (3) a targeted, Internet-based advertising campaign. We evaluated (a) completion of matching tool, (b) expression of interest in a clinical trial, (c) number of patients who matched to clinical trials at a single institution, (d) discussion of risks and benefits of clinical trials (via follow-up interviews), and (e) effect of the advertising on completing the matching tool. Feasibility, acceptability, and preliminary estimates of efficacy were measured through user engagement with the matching tool and subsequent qualitative interviews with these same users.ResultsDuring the 28-week study period, 523 users provided demographic information, 263 were identified with prostate cancer, 192 (73%) matched to at least one clinical trial, and 29 (15.1%) of those who matched provided contact information. During the study period, 17 prostate cancer clinical trials were available for matching. We completed follow-up interviews with 14 of the 29 men who provided contact information. Of the 14, 85.7% discussed the risks and benefits of clinical trials with their physician, and 35.7% enrolled in a clinical trial. The Internet-based advertising campaign resulted in an increased number of matching tool completions.ConclusionsOur study demonstrates that an Internet-based clinical trial matching tool that is advertised using a targeted Internet-based campaign can provide an effective means to reach diverse, low-literacy patients. When implemented at scale and over a longer duration, such interventions may help increase trial participation among underrepresented populations.

Pilot randomized trial of a telephone-delivered physical activity and weight management intervention for individuals with lower extremity amputation

BackgroundObesity and inactivity are common and burdensome for people with lower extremity amputation (LEA). The extent to which home-based physical activity/weight management programs are effective and safe for people with LEA is unknown. Translating effective interventions for understudied disability groups is needed. ObjectiveTo test the feasibility, acceptability, and safety of a weight management and physical activity intervention and obtain preliminary efficacy estimates for changes in weight, body composition, and physical functioning. MethodsEligibility criteria included: LEA ≥1 year prior, 18–69 years of age, overweight or obese and living in the Seattle area. The intervention arm received self-monitoring tools (e.g., pedometer, scale) and written materials, a single exercise counseling home visit by a physical therapist, and up to 11 telephone calls from a health coach over 20 weeks that involved motivational interviewing to set specific, attainable, and measurable goals. The self-directed control group received the same tools and materials but no home visit or coaching calls. ResultsNineteen individuals consented to participate, 15 were randomized (mean age = 56, 73% male, 80% transtibial amputation) and 11 completed 20-week follow-up assessments. The intervention was acceptable and safe. Coached participants had greater decreases in waist circumference (mean difference between groups over 20 weeks, baseline values carried forward: −4.3 cm, 95% CI -8.2, −0.4, p = 0.03) and fat mass (−2.1 kg, 95% CI -3.8, −0.4, p = 0.02). ConclusionsThe home-based intervention was promising in terms of efficacy, safety and acceptability. Inclusion of multiple trial centers and increased use of technology may facilitate recruitment and retention.