Feasibility Of Clinical Trial Research Articles

Mobile phone virtual reality game for pediatric home burn dressing pain management: a randomized feasibility clinical trial

BackgroundVirtual reality (VR) gaming is considered a safe and effective alternative to standard pain alleviation in the hospital. This study addressed the potential effectiveness and feasibility of a VR game that was developed by our research team for repeated at-home burn dressing changes.MethodsA randomized clinical trial was conducted among patients recruited from the outpatient burn clinic of a large American Burn Association–verified pediatric burn center between September 2019 and June 2021. We included English-speaking burn patients aged 5–17 years old requiring daily dressing changes for at least 1 week after first outpatient dressing change. One group played an interactive VR game during dressing changes, while the other utilized standard distraction techniques available in the home for up to a week. Both child and caretaker were asked to assess perceived pain on a numerical rating scale (NRS) of 0–10. For the VR group, patients were also asked to rate various aspects of the VR game on a NRS of 0–10 and caregivers were asked questions assessing ease of use.ResultsA total of 35 children were recruited for this study with 24 fully completing study measures. The majority of participants were male (n=19, 54.3%), White (n=29, 82.9%), and with second degree burns (n=32, 91.4%). Children and caregivers in the VR group reported less pain than the control group at the 4th dressing change. Participants in the VR group showed a clinically meaningful (≥30%) reduction in child-reported overall pain (33.3%) and caregiver-reported worst pain (31.6%) in comparison with subjects in the control group. Children’s satisfaction with the VR remained at a high level across dressing changes over the 1-week period, with reported realism and engagement increasing over time. Over half of the children (54.5%) enjoyed playing the game and did not report any challenges nor any side effects.ConclusionsSubjects found the VR to be a useful distraction during home dressing changes and reported no challenges/side effects. VR should be considered as a nonpharmacologic companion for pain management during at-home burn dressing changes.Trial registrationClinicalTrials.gov Identifier: NCT04548635. Registered September 14, 2020—retrospectively registered

Short-term and long-term outcomes of zirconium dioxidebased dental restorations, and it effects on masticatory function

Purpose: To investigate the short- and long-term outcomes of zirconium dioxide-based restorations (ZDBR), and changes in masticatory function (MF).Methods: One hundred and two (102) patients who received restorative dentistry procedures were divided into two groups using random number method: control group (CG, n = 52, alloy-based restorations) and study group (SG, n = 50, zirconium dioxide restorations). Treatment efficacy, quality, levels of IL-8 and IL-6 in gingival sulcus fluid, and satisfaction scores were compared.Results: The SG showed better outcomes and restoration quality than CG. After restoration, SG showed greater decrease in IL-8 and IL-6 levels than CG (p < 0.05), while IL-8 and IL-6 levels were higher in SG and CG than those before restoration (p < 0.05). After 1 and 6 months of restoration, SG showed increased dental appearance satisfaction and a higher success rate than CG (p < 0.05). Occlusal force and MF were significantly improved in both groups (p < 0.05). Gingival index, bleeding index, plaque index, and tooth looseness after restoration significantly improved in both groups, but were lower in SG than in CG (p < 0.05).Conclusion: In oral restorations, ZDBR is more effective in terms of short-term and long-term outcomes. Patients' occlusal force and MF are better restored, and patients' quality of life is also significantly improved. Therefore, ZDBR in oral restorations is feasible but further clinical trials are required.

Understanding the Neurofibromatosis Type 1 (NF1) experience and the priorities of individuals with NF1 and their caregivers for cognitive and social-emotional research

BackgroundPatient engagement is increasingly recognized as a valuable, essential aspect of Neurofibromatosis research given the unique experiences and morbidities associated with the diagnosis. Engaging patients and families can enhance the relevance, methodology, and feasibility of clinical trials. MethodsA REDCap survey ascertaining information on NF-related morbidities, priorities, and interests in cognitive and social-emotional research, and willingness to participate in research was dispensed to 4,565 individuals consented to the Children's Tumor Foundation (CTF) Registry with NF1. This included children and adults with NF1 and parents/caregivers of children with NF1. Results525 individuals fully completed the survey: 295 parents/caregivers (Mage child = 10.12, range = 3–24), 194 adults with NF1 (Mage = 45.73, range = 19–81), and 36 children with NF1 (Mage = 12.61, range = 10–17). Less than 10% of respondents have participated in cognitive research, while 42.4–49.5% indicated having sought opportunities for cognitive research. Most (79.4–82.4%) respondents reported that cognitive research is very/extremely important, with learning/academics and emotional functioning were priorities. Willingness to participate in research aligned with areas of importance. ConclusionAnalysis highlights that most survey respondents believe cognitive and social-emotional research is very important, but a relatively small number have participated. This finding may highlight poor dissemination of information of research opportunities to the broader NF community and limitations to access based on geography or other factors. Respondents indicate that learning/academic problems and emotional challenges to be research priorities. Continuing to engage patients and families with NF is expected to enhance the value and engagement in cognitive research.

Feasibility of international trials of rare epithelial ovarian cancers based on trends in the United States and Asia (163)

Objectives: To investigate the feasibility of international clinical trials in rare ovarian cancers by first studying the incidence and trends of the rare histologic subtypes in the United States (US) and Asia. Methods: Data were obtained from the United States Cancer Statistics (USCS) Public Use Databases and Taiwan Cancer Registry of Taiwan Health and Welfare Data Center (HWDC) for a diagnosis of ovarian clear cell carcinoma, endometrioid carcinoma, mucinous carcinoma, or carcinosarcoma between 2001 to 2017. SEER*Stat 8.3.9, Joinpoint regression program 4.8.0.1, and Excel were used to calculate the incidence and trends. Results: In 2017, the incidence of ovarian clear cell carcinoma, endometrioid carcinoma, mucinous carcinoma, or carcinosarcoma was 0.81, 0.51, 0.47, or 0.25 per 100,000 in the US, and 1.58, 1.17, 1.08, or 0.15 per 100,000 in Asia, respectively. Over the last 18 years, the average annual percent change (AAPC) in clear cell carcinoma did not change in the US and increased by 6.2% in Asia. The AAPC for ovarian endometrioid carcinoma decreased by 2.7% in the US and increased by 2.9% in Asia. Although the rate of carcinosarcoma is increasing in both the US and Asia, it is 16-fold higher in Asia compared with the US, with an AAPC for ovarian carcinosarcoma of 6.4% in Asia versus 0.4% in the US. The rate of ovarian mucinous carcinoma decreased in both the US and Asia with an AAPC of 2.0% versus 0.9%, respectively. Conclusions: The AAPC of ovarian clear cell carcinoma, endometrioid carcinoma, and carcinosarcoma is increasing at higher rates in Asia than in the US, providing justification to utilize global recruitment strategies for clinical trial investigational treatments and interventions in rare ovarian cancers. Objectives: To investigate the feasibility of international clinical trials in rare ovarian cancers by first studying the incidence and trends of the rare histologic subtypes in the United States (US) and Asia. Methods: Data were obtained from the United States Cancer Statistics (USCS) Public Use Databases and Taiwan Cancer Registry of Taiwan Health and Welfare Data Center (HWDC) for a diagnosis of ovarian clear cell carcinoma, endometrioid carcinoma, mucinous carcinoma, or carcinosarcoma between 2001 to 2017. SEER*Stat 8.3.9, Joinpoint regression program 4.8.0.1, and Excel were used to calculate the incidence and trends. Results: In 2017, the incidence of ovarian clear cell carcinoma, endometrioid carcinoma, mucinous carcinoma, or carcinosarcoma was 0.81, 0.51, 0.47, or 0.25 per 100,000 in the US, and 1.58, 1.17, 1.08, or 0.15 per 100,000 in Asia, respectively. Over the last 18 years, the average annual percent change (AAPC) in clear cell carcinoma did not change in the US and increased by 6.2% in Asia. The AAPC for ovarian endometrioid carcinoma decreased by 2.7% in the US and increased by 2.9% in Asia. Although the rate of carcinosarcoma is increasing in both the US and Asia, it is 16-fold higher in Asia compared with the US, with an AAPC for ovarian carcinosarcoma of 6.4% in Asia versus 0.4% in the US. The rate of ovarian mucinous carcinoma decreased in both the US and Asia with an AAPC of 2.0% versus 0.9%, respectively. Conclusions: The AAPC of ovarian clear cell carcinoma, endometrioid carcinoma, and carcinosarcoma is increasing at higher rates in Asia than in the US, providing justification to utilize global recruitment strategies for clinical trial investigational treatments and interventions in rare ovarian cancers.

A High Fidelity and High Frequency Physical Simulator for Mitral Annulus Kinematics

Cardiovascular medical devices that operate within the heart are subjected to millions of loading cycles that can compromise the structural integrity of the implant over time. Accelerated structural testing is a major challenge in the design of implantable cardiac devices, particularly in the emerging realm of catheter-based devices used to treat conditions like mitral valve regurgitation (MR). In this work, we design a bench-top simulator for accelerated structural testing of devices that operate in or near the mitral valve. We first use four-dimensional computed tomography (4DCT) data to create a molded replica of the mitral valve and identify the most deformation-inducing time points in the cardiac cycle. We then kinematically analyze the motion of the mitral annulus using screw theory and create an electromechanical simulation device that mimics this motion at high frequencies. The final apparatus allows for multiple patient-specific scenarios and accurate closed loop displacement control of the screw-based kinematics of the mitral annulus. The test apparatus operates with less than 1 dB of passband ripple up to its 25.7 Hz bandwidth. The proposed device moves toward a desirable paradigm in accelerated structural testing that is less reliant on computational models, animal models, and high-risk early feasibility clinical trials.

Source localized infraslow neurofeedback training in people with chronic painful knee osteoarthritis: A randomized, double-blind, sham-controlled feasibility clinical trial.

Persistent pain is a key symptom in people living with knee osteoarthritis (KOA). Infra-slow Neurofeedback (ISF-NF) training is a recent development focusing on modulating cortical slow-wave activity to improve pain outcomes. A parallel, two-armed double-blinded, randomized sham-controlled, feasibility clinical trial aimed to determine the feasibility and safety of a novel electroencephalography-based infraslow fluctuation neurofeedback (EEG ISF-NF) training in people with KOA and determine the variability of clinical outcomes and EEG changes following NF training. Eligible participants attended nine 30-min ISF-NF training sessions involving three cortical regions linked to pain. Feasibility measures were monitored during the trial period. Pain and functional outcomes were measured at baseline, post-intervention, and follow-up after 2 weeks. Resting-state EEG was recorded at baseline and immediate post-intervention. Participants were middle-aged (61.7 ± 7.6 years), New Zealand European (90.5%), and mostly females (62%) with an average knee pain duration of 4 ± 3.4 years. The study achieved a retention rate of 91%, with 20/22 participants completing all the sessions. Participants rated high levels of acceptance and “moderate to high levels of perceived effectiveness of the training.” No serious adverse events were reported during the trial. Mean difference (95% CI) for clinical pain and function measures are as follows for pain severity [active: 0.89 ± 1.7 (−0.27 to 2.0); sham: 0.98 ± 1.1 (0.22–1.7)], pain interference [active: 0.75 ± 2.3 (−0.82 to 2.3); Sham: 0.89 ± 2.1 (−0.60 to 2.4)], pain unpleasantness [active: 2.6 ± 3.7 (0.17–5.1); sham: 2.8 ± 3 (0.62–5.0)] and physical function [active: 6.2 ± 13 (−2.6 to 15); sham: 1.6 ± 12 (−6.8 to 10)]. EEG sources demonstrated frequency-specific neuronal activity, functional connectivity, and ISF ratio changes following NF training. The findings of the study indicated that the ISF-NF training is a feasible, safe, and acceptable intervention for pain management in people with KOA, with high levels of perceived effectiveness. The study also reports the variability in clinical, brain activity, and connectivity changes following training.

The tumor core boost study: A feasibility study of radical dose escalation to the central part of large tumors with an integrated boost in the palliative treatment setting

PurposeFor patients with large tumors palliative radiotherapy often is the only local treatment option. To prevent toxicity the administered doses are low. Dose escalation to the tumor could be an option to better smyptom control and prolong local control rates. In this prospective study we used a very pragmatic approach with a simultaneously integrated boost (SIB) to an almost geometrically defined tumor core to achieve this. The primary endpoint was to demonstrate feasibility.MethodPatients with solid tumors > 4 cm in diameter of different histologies were eligible in this single arm, prospective, multi-institutional clinical feasibility trial with two treatment concepts: 5 × 5 Gy with an integrated boost to the tumor core of 5 × 10 Gy or 10 × 3 Gy with a boost of 10 × 6 Gy. The objective of dose escalation in this study was to deliver a minimum dose of 150% of the prescribed dose to the gross tumor volume (GTV) tumor core and to reach a maximum of at least 200% in the tumor core.ResultsIn all, 21 patients at three study sites were recruited between January 2019 and November 2020 and were almost evenly spread (9 to 12) between the two concepts. The treated planning target volumes (PTV) averaged 389.42 cm3 (range 49.4–1179.6 cm3). The corresponding core volumes were 72.85 cm3 on average (range 4.21–338.3 cm3). Dose escalation to the tumor core with mean doses of 167.7–207.7% related to the nonboost prescribed isodose led to PTV mean doses of 120.5–163.3%. Treatment delivery and short-term follow-up was successful in all patients.ConclusionsPalliative radiotherapy with SIB to the tumor core seems to be a feasible and well-tolerated treatment concept for large tumors. The applied high doses of up to 50 Gy in 5 fractions (or 60 Gy in 10 fractions) did not cause unexpected side effects in the 42 day follow-up period. Further research is needed for more information on efficacy and long-term toxicity.

Intervention in Older Urban-Dwelling Veterans With Dysmobility: Protocol for a Pilot Feasibility Clinical Trial.

BackgroundThe majority of older veterans do not meet the minimum healthy diet or physical activity recommendations despite known benefits. Identifying ways to increase adherence to programs that improve dietary quality and physical activity may reduce the risk of disability in older veterans. Peer-based interventions may be one method for facilitating lasting behavior change because peers often share a common culture and knowledge regarding problems their community experiences.ObjectiveThis study aims to develop, pilot, and evaluate a theory-driven, 12-week, peer-led nutrition and exercise intervention that targets older veterans with dysmobility and assess its feasibility in 2 diverse urban areas with underrepresented populations.MethodsCommunity-dwelling veterans aged >65 years with self-reported dysmobility (defined as difficulty in at least 1 of the following: walking quickly across a street, walking a mile, ascending a flight of stairs, rising from a chair without the use of arms, or a fear of falling) from 2 Department of Veterans Affairs Geriatric Research, Education, and Clinic Centers (Baltimore, Maryland, and San Antonio, Texas) will be eligible to participate. First, this study will use validated mixed methods via web-based surveys (n=50 per site) to assess potential physical, social or environmental, and behavioral or lifestyle barriers that affect physical activity and dietary quality (phase 1). Next, we will use knowledge gained from these assessments and feedback from a focus group (n=10 per site) to adapt established Department of Veterans Affairs diet and exercise program materials to develop peer-led intervention materials and train peer leaders (n=3 per site). Finally, we will determine the feasibility and acceptability of the intervention to assess reach (recruitment and retention), adoption (satisfaction, perceived utility, attendance, and engagement), and implementation (fidelity of intervention), as well as the estimated magnitude and potential impact on selected outcomes (ie, diet quality and mobility) in 20 older veterans with dysmobility (n=10 per site).ResultsThe study was funded on January 1, 2022, with a projected data collection period of June 1, 2022, to December 31, 2023.ConclusionsThis study offers an innovative approach to identifying strategies that increase long-term adherence to lifestyle modification programs that improve dietary quality and physical activity in older veterans with dysmobility.Trial RegistrationClinicalTrials.gov NCT04994938; https://clinicaltrials.gov/ct2/show/NCT04994938International Registered Report Identifier (IRRID)PRR1-10.2196/39192

P-488 Perceptions of gamete and embryo donation recipient parents about the online experimental and control programs in the TELL Tool feasibility clinical trial at immediate post-test

Abstract Study question What are parents’ initial perceptions about the online experimental and control programs at immediate post-test? Summary answer Parents reported overall acceptability of the online instructions, technological navigation, length, and quality of videos, as well as suggestions for further improvement. What is known already Multiple investigations have examined the reasons why parents who used donated gametes or embryos, decide to inform their children that they were conceived through third-party reproduction. A consistent theme in this research is parental calls for strategies and tools to aid parents with disclosure to their children. Despite these calls from parents, little research has focused on developing new methods of delivering parent-focused materials that aim to assist parents in their disclosure process. To address this concern, we developed an online experimental program called the Tool to Empower Parental TeLling and TaLking (TELL Tool) and completed alpha testing. Study design, size, duration A 3-month feasibility clinical trial. Participants/materials, setting, methods Donor sperm, egg, and embryo recipient parents were randomized to either an experimental TELL Tool program or a control program focused on good parenting practices. Both the TELL Tool and the control programs are administered online. To date 13 parents have completed the experimental or control program and each participant has answered an immediate post-test survey about the acceptability of the program. Descriptive statistics and qualitative content analysis guided the analysis. Main results and the role of chance The sample consists of 13 U.S. parents between 35 to 53 years (M = 41.3 years). The parents used donated sperm (n = 5), eggs (n = 2), sperm and eggs (n = 2) or embryos (n = 4) and their children were between 1 to 12 years (M = 5.7 years). Most parents were female (n = 11) and White (n = 10). Parents were asked to rate the level of truthfulness about the acceptability of the online programs (ratings: 1 to 5, with 1 being “not at all true” to 5 being “very true”). Responses about the: (1) instructions provided for accessing the program were easy, were: range 3 to 5, M = 3.9; (2) technological navigation within the program was problematic, were: range 1 to 5, M = 2.7; (3) length of the program was too long, were: range 1 to 5, M = 3; and (4) videos within the program were helpful, were: range 3 to 5, M = 3.69. Responses to the open-ended questions provided insights to the ratings, such as parents’ statements about specific technological issues (e.g., ability to print resources, ease of navigating in-and-out of the program). Limitations, reasons for caution Preliminary data are reported for the feasibility trial at the immediate post-test timepoint as recruitment is ongoing. As the 3-month study unfolds, additional data will be obtained to allow for more in-depth understanding of parents’ perceptions about the acceptability of the experimental TELL Tool and control programs. Wider implications of the findings The acceptability of the online research for donor gamete and embryo recipient parents may illuminate access issues to these often hidden and dispersed parents and their families across the lifespan. Parents’ responses can provide a window of understanding for other decision aids that target health promotion among parents and children. Trial registration number NCT04841967

Rehabilitation of Upper Extremity by Telerehabilitation Combined With Exergames in Survivors of Chronic Stroke: Preliminary Findings From a Feasibility Clinical Trial.

BackgroundExergames are increasingly being used among survivors of stroke with chronic upper extremity (UE) sequelae to continue exercising at home after discharge and maintain activity levels. The use of virtual reality exergames combined with a telerehabilitation app (VirTele) may be an interesting alternative to rehabilitate the UE sequelae in survivors of chronic stroke while allowing for ongoing monitoring with a clinician.ObjectiveThis study aimed to determine the feasibility of using VirTele in survivors of chronic stroke at home and explore the impact of VirTele on UE motor function, quantity and quality of use, quality of life, and motivation in survivors of chronic stroke compared with conventional therapy.MethodsThis study was a 2-arm feasibility clinical trial. Eligible participants were randomly allocated to an experimental group (receiving VirTele for 8 weeks) or a control group (receiving conventional therapy for 8 weeks). Feasibility was measured from the exergame and intervention logs completed by the clinician. Outcome measurements included the Fugl-Meyer Assessment-UE, Motor Activity Log-30, Stroke Impact Scale-16, and Treatment Self-Regulation Questionnaire-15, which were administered to both groups at four time points: time point 1 (T1; before starting the intervention), time point 2 (after the intervention), time point 3 (1 month after the intervention), and time point 4 (T4; 2 months after the intervention).ResultsA total of 11 survivors of stroke were randomized and allocated to an experimental or a control group. At the onset of the COVID-19 pandemic, participants pursued the allocated treatment for 3 months instead of 8 weeks. VirTele intervention dose was captured in terms of time spent on exergames, frequency of use of exergames, total number of successful repetitions, and frequency of videoconference sessions. Technical issues included the loss of passwords, internet issues, updates of the system, and problems with the avatar. Overall, most survivors of stroke found the technology easy to use and useful, except for 9% (1/11) of participants. For the Fugl-Meyer Assessment-UE and Motor Activity Log-30, both groups exhibited an improvement in >50% of the participants, which was maintained over time (from time point 3 to T4). Regarding Stroke Impact Scale-16 scores, the control group reported improvement in activities of daily life (3/5, 60%), hand function (5/5, 100%), and mobility (2/5, 40%), whereas the experimental group reported varied and inconclusive results (from T1 to T4). For the Treatment Self-Regulation Questionnaire-15, 75% (3/4) of the experimental group demonstrated an increase in the autonomous motivation score (from T1 to time point 2), whereas, in the control group, this improvement was observed in only 9% (1/11) of participants.ConclusionsThe VirTele intervention constitutes another therapeutic alternative, in addition to conventional therapy, to deliver an intense personalized rehabilitation program for survivors of chronic stroke with UE sequelae.International Registered Report Identifier (IRRID)RR2-10.2196/14629

Breaking Down Barriers to Precision Oncology Care

Breaking Down Barriers to Precision Oncology Care

Perioperative optimization with nutritional supplements in patients undergoing gastrointestinal surgery for cancer: A randomized, placebo-controlled feasibility clinical trial

BackgroundPerioperative nutritional supplementation may improve outcomes. Trials have not investigated the role of combination strategy using different types of nutritional supplements. MethodsWe conducted a single-site randomized pilot trial, among gastrointestinal cancer patients undergoing surgery, comparing perioperative nutritional supplements versus placebo (1 placebo to each supplement), to determine feasibility of a larger trial. Intervention, administered in sequence, included: protein supplementation (preoperative day 30–6), protein supplementation rich in arginine and omega-6 (preoperative day 5–1, and postoperative day 1–5), and carbohydrate loading (surgery day). Primary outcome was enrollment. Secondary outcomes included participant compliance with study supplements (target ≥70% of total packets). We planned protocol modifications to improve enrollment and compliance. Postoperative complications were described. ResultsOver 18 months, 495 patients were screened, 144 were deemed eligible, and 71 consented to participate, resulting in an enrollment fraction of 71/144 (49%, 95% confidence interval: 41%–57%). ‘Too much burden’ was the most common reason for refusal to participate (34%). Participants’ median overall compliance with study packets was 80%. Protocol modifications (decreasing the interval from enrollment to surgery from 4 to 2 weeks and decreasing length of baseline assessment) did not impact enrollment or compliance. Postoperative complications were similar between control (18/31 [58%, 95% confidence interval: 4–74]), and intervention (22/34 [65%, 95% confidence interval: 48–79]) arms, with a higher proportion of infectious complications in the control arm (16/31, 52% vs 12/34, 35%). ConclusionResults from this pilot suggest a larger phase III trial is feasible. Postoperative infectious complications were common, making this a suitable outcome of interest.

Scoping review and characteristics of publicly available checklists for assessing clinical trial feasibility

BackgroundWhether there is sufficient capacity and capability for the successful conduct and delivery of a clinical trial should be assessed by several stakeholders according to transparent and evidence-based criteria during trial planning. For this openly shared, user-tested, and validated tools are necessary. Therefore, we systematically examined the public availability and content of checklists which assess the study-level feasibility in the planning phase of clinical trials.MethodsIn our scoping review we systematically searched Medline, EMBASE, and Google (last search, June 2021). We included all publicly available checklists or tools that assessed study level feasibility of clinical trials, examined their content, and checked whether they were user-tested or validated in any form. Data was analysed and synthesised using conventional content analysis.ResultsA total of 10 publicly available checklists from five countries were identified. The checklists included 48 distinct items that were classified according to the following seven different domains of clinical trial feasibility: regulation, review and oversight; participant recruitment; space, material and equipment; financial resources; trial team resources; trial management; and pilot or feasibility studies. None of the available checklists appeared to be user-tested or validated.ConclusionsAlthough a number of publicly available checklists to assess the feasibility of clinical trials exist, their reliability and usefulness remain unclear. Openly shared, user-tested, and validated feasibility assessment tools for a better planning of clinical trials are lacking.

Feasibility of online behavioral clinical trials: The future of weight management randomized clinical trials?

Behavioral weight management trials are traditionally conducted in-person. The COVID-19 shutdown halted in-person operations, forcing investigators to develop new methods for remote treatment and assessment delivery without additional funding for website development or remote equipment. This study examined the feasibility and acceptability of remote procedures from an ongoing weight management trial impacted by COVID-19. Using a quasi-experimental longitudinal design, in-person (pre-COVID) and remote (COVID) treatment and assessment procedures were used. Attendance at in-person versus remote (videoconference) treatment sessions was compared. Acceptability of treatment modalities (in-person vs. remote) was examined via self-report. Validity and reliability were assessed on bathroom scales. Attendance at remote (videoconference+mailed, scales) versus in-person assessment sessions was compared. Finally, exploratory analyses were conducted to determine whether participant characteristics moderated the effects. Remote treatment attendance was significantly better than in-person. Overall, there was no significant difference in modality preference. However, Hispanic (vs. non-Hispanic) individuals had greater preference for remote options and attended more remote treatment sessions. Bathroom scales demonstrated excellent validity and reliability. Adherence to remote and in-person assessment sessions was similar. COVID-19 has provided an opportunity to rethink how we conduct research. Results herein establish an evidence-base to support a paradigm shift to remote clinical trial procedures. Such a shift may enhance diversity in clinical trials.

PROPHETIC EU: Prospective Identification of Pneumonia in Hospitalized Patients in the Intensive Care Unit in European and United States Cohorts.

BackgroundThe prospective identification of patients at high risk for hospital-acquired/ventilator-associated bacterial pneumonia may improve clinical trial feasibility and foster antibacterial development. In a prior study conducted in the United States, clinical criteria were used to prospectively identify these patients; however, these criteria have not been applied in a European population.MethodsAdults considered high risk for pneumonia (treatment with ventilation or high levels of supplemental oxygen) in the intensive care units of 7 European hospitals were prospectively enrolled from June 12 to December 27, 2017. We estimated the proportion of high-risk patients developing pneumonia according to US Food and Drug Administration guidance and a subset potentially eligible for antibacterial trial enrollment. We compared patient characteristics, treatment exposures, and pneumonia incidence in a European cohort and a previously described US cohort.ResultsOf 888 high-risk patients, 211/888 (24%) were treated for possible pneumonia, and 150/888 (17%) met the Food and Drug Administration definition for hospital-acquired/ventilator-associated bacterial pneumonia. A higher proportion of European patients treated for possible pneumonia met the pneumonia definition (150/211 [71%] vs 537/1464 [37%]; P < .001). Among patients developing pneumonia, a higher proportion of European patients met antibacterial trial eligibility criteria (124/150 [83%] vs 371/537 [69%]; P < .001).ConclusionsClinical criteria prospectively identified high-risk patients with high rates of pneumonia in the European cohort. Despite higher rates of established risk factors and incident pneumonia, European patients were significantly less likely to receive antibiotics for possible pneumonia than US patients. Different treatment practices may contribute to lower rates of antibacterial trial enrollment in the United States.

MO580: Healthy Plant-Based Diet for Patients With Chronic Kidney Disease (CKD) Through Use of Sodium Zirconium Cyclosilicate (SZC): A Feasibility Study (Helpful)

Abstract BACKGROUND AND AIMS Healthy plant-based diets (HealthyPB diet) may offer metabolic and cardiovascular benefits to patients with CKD. However, the higher potassium (K+) content of these diets is a concern when prescribed to CKD patients with hyperkalemia (HK). Potassium-lowering medication, such as SZC, can be a treatment option to allow better control of plasma K + for those ingesting a HealthyPB diet. We investigated whether patients with CKD stage 4–5 and HK can be safely prescribed a HealthyPB diet with increased K + content by concomitant use of SZC. METHOD This is an ongoing open label feasibility clinical trial that will include 36 patients with CKD stage 4–5 not on dialysis with HK (plasma K+ ≥ 5.1 mmol/L). Patients with plasma K+ &amp;gt; 6.5 mmol/L are excluded. Intervention: Patients are followed for 6 weeks. In the first 3 weeks (stabilization phase), SZC is prescribed according to the drug label to normalize plasma K + while ingesting a low protein diet (0.6–0.8 g/kg/day) with low content of K+ (2.3 g/day) as counselled by a dietitian. After 3 weeks, patients initiate and follow for 3 additional weeks, the HealthyPB diet containing unchanged low amount of protein and K + content of 3.7–4 g/day. In order to increase diet adherence, a food basket (containing fruits, vegetables, whole grains, nuts, whole cereals, white meat, fish or eggs in amounts adequate for the patient and the family) is delivered to patient's home once per week. Serum K is closely monitored and the dose of SZC is adjusted according to the drug label to maintain serum K between 3.5 and 5.0 mmol/L. Adherence to the diet is assessed by 24-h urinary K + excretion, 24-h food record, and a semi-quantitative short food questionnaire at the beginning and end of the stabilization phase and again at the beginning and end of the HealthyPB diet phase. The protocol is registered at www.clinicaltrials.gov (identifier NCT04207203). RESULTS Among 14 patients included so far, 12 completed the study protocol and 2 are being followed. Results in the patients (n = 12; age 56.5 ± 10 years; 66.7% men; eGFR: 16.4 ± 4.6 mL/min/1.73 m2) who completed the follow-up are described in the Table 1. Mean ± SD or median and interquartile range; NA: not assessed. At the end of follow-up three (25%) patients had plasma K + between 5.1 and 5.3 mmol/L. CONCLUSION These preliminary results indicate that patients adhered to the low protein HealthyPB diet with an increase in the intake of fruits, vegetables, whole cereals and nuts. The mean plasma K + was well controlled with SZC and within the normal range after the start of the HealthyPB diet.

Optimization of expansion techniques for adoptive NK cell transfer in dogs with cancer

Abstract Natural killer (NK) cells can recognize heterogeneous cancer cell targets without prior sensitization, making them promising prospects for use in immunotherapy. We have completed first-in-dog feasibility clinical trials in dogs with cancer using both autologous and allogeneic NK cells expanded from peripheral blood mononuclear cells (PBMCs). Previously, CD5 depletion of PBMCs has been used to enrich for a CD5dim expressing subset prior to NK co-culture with an irradiated feeder line, but this can limit the yield of the final NK product. The purpose of this study was to compare ex vivo culture conditions using standard CD5 depletion versus unmanipulated PBMCs plus feeder line co-culture with 100 IU/mL rhIL-2 in matched healthy donors, hypothesizing that PBMCs plus feeder cells would generate an equivalent or superior NK product to CD5 depletion. Cell count, fold change, and viability data were collected for both techniques in 12 dogs across five time points up to day 14. A mixed-effects model analysis showed no statistical difference in calculated cell counts, overall fold change, and viability (p&amp;gt;0.05 all) between PBMCs with feeders and CD5 depleted cells with feeders. PBMCs had a higher mean than CD5 depleted cells at day 14 in all three categories, reaching a peak mean of 677 million cells from 5 million PBMCs at day 0. Flow phenotype showed similar upregulation of NKp46 and Granzyme B expression. Killing assays against melanoma and osteosarcoma targets demonstrated comparable results among PBMCs plus feeders versus CD5 depleted NK cells (p&amp;gt;0.05). Overall, these findings support the use of unmanipulated PBMCs plus feeder line coculture as an equivalent method to CD5 depletion in the expansion of canine NK cells for adoptive immunotherapy. Supported by grants from National Institutes of Health/National Cancer Institute (U01 CA224166-01, 1R03CA252793, T32 CA251007-01)

Six-Month Outcomes of Reimplantation of a Coin-Sized Tibial Nerve Stimulator for the Treatment of Overactive Bladder Syndrome With Urgency Urinary Incontinence.

ObjectiveThe eCoin (Valencia Technologies Corporation, Valencia, CA) is a battery-powered, nickel-sized and shaped neuromodulation device for the treatment of overactive bladder, and it is implanted in the lower leg in a short office or outpatient procedure under local anesthesia. A follow-on trial was conducted to evaluate the feasibility, safety, and efficacy of eCoin reimplantation.MethodsThis was a prospective, single-arm, open-label study, including 23 participants with refractory urgency urinary incontinence (UUI) who were previously participants in the eCoin clinical feasibility trial. This follow-on study was conducted at 7 sites in the United States and New Zealand. Participants were reimplanted with a new eCoin device and activated after 4 weeks. Bladder diary data and validated quality-of-life instruments, collected at 12 weeks and 24 weeks postactivation, were compared with baseline.ResultsParticipants of the study were considered responders if they reported a ≥ 50% reduction from baseline in episodes of UUI on a 3-day voiding diary. At 12 weeks of treatment, 74% (95% confidence interval [CI], 52%–90%) of participants were considered responders. At 24 weeks of treatment, 82% (95% CI, 60%–95%) of participants were considered responders with 36% (95% CI, 20%–57%) of participants achieving complete continence. There were no device-related serious adverse events reported during the study.ConclusionsThe reimplantation of eCoin was both safe and effective in treating UUI associated with overactive bladder syndrome. The demonstrated significant reduction or resolution of symptoms with no serious safety concern suggests that eCoin is a convenient and maintainable therapeutic device.

Tolerability and feasibility of at-home remotely supervised transcranial direct current stimulation (RS-tDCS): Single-center evidence from 6,779 sessions

IntroductionThe ability to deploy transcranial direct current stimulation (tDCS) at home is a key usability advantage to support scaling for pivotal clinical trials. We have established a home-based tDCS protocol for use in clinical trials termed remotely supervised (RS)-tDCS. ObjectiveTo report the tolerability and feasibility of tDCS sessions completed to date using RS-tDCS in clinical trials. MethodsWe analyzed tolerability (i.e., adverse events, AEs) reported in six Class I/II/III trials using RS-tDCS to study symptom outcomes over 10 to 60 daily applications. Across the six clinical trials, 308 participants (18–78 years old) completed an average of 23 sessions for a total of 6779 RS-tDCS administrations. The majority of participants were diagnosed with multiple sclerosis, and open-label trials included those diagnosed with a range of other conditions (e.g., Parkinson's disease, post-stroke aphasia, traumatic brain injury, cerebellar ataxia), with minimum-to-severe neurologic disability. Clinical trial feasibility (i.e., treatment fidelity and blinding integrity) was examined using two Class I randomized controlled trials (RCTs). ResultsNo serious AEs occurred. Across administrations, three sessions (0.04%) were aborted due to discomfort, but no participant discontinued due to tolerability. The AEs most commonly reported by participants were tingling (68%), itching (41%) and warmth sensation (42%) at the electrode site, and these were equally reported in active and sham tDCS conditions. The two Class I RCTs resulted in rapid enrollment, high fidelity to treatment completion, and blinding integrity. ConclusionsAt-home RS-tDCS is tolerable, including when used over extended periods of time. Home-based RS-tDCS is feasible and can enable Class I tDCS clinical trial designs.

Equipoise in Clinical Trials: Enough Uncertainty in Whose Opinion?

Equipoise in Clinical Trials: Enough Uncertainty in Whose Opinion?