Pilot Randomized Clinical Trial Research Articles

Glycine by enteral route does not improve major clinical outcomes in severe COVID-19: a randomized clinical pilot trial

There is a worrying scarcity of drug options for patients with severe COVID-19. Glycine possesses anti-inflammatory, cytoprotective, endothelium-protective, and platelet-antiaggregant properties, so its use in these patients seems promising. In this open label, controlled clinical trial, inpatients with severe COVID-19 requiring mechanical ventilation randomly received usual care (control group) or usual care plus 0.5 g/kg/day glycine by the enteral route (experimental group). Major outcomes included mortality, time to weaning from mechanical ventilation, total time on mechanical ventilation, and time from study recruitment to death. Secondary outcomes included laboratory tests and serum cytokines. Patients from experimental (n = 33) and control groups (n = 23) did not differ in basal characteristics. There were no differences in mortality (glycine group, 63.6% vs control group, 52.2%, p = 0.60) nor in any other major outcome. Glycine intake was associated with lower fibrinogen levels, either evaluated per week of follow-up (p < 0.05 at weeks 1, 2, and 4) or as weighted mean during the whole hospitalization (608.7 ± 17.7 mg/dl vs control 712.2 ± 25.0 mg/dl, p = 0.001), but did not modify any other laboratory test or cytokine concentration. In summary, in severe COVID-19 glycine was unable to modify major clinical outcomes, serum cytokines or most laboratory tests, but was associated with lower serum fibrinogen concentration.Registration: ClinicalTrials.gov NCT04443673, 23/06/2020.

Repetitive Transcranial Magnetic Stimulation for Executive Functioning in Veterans with TBI and PTSD: Clinical Outcomes and Connectivity Changes in a Pilot Randomized Clinical Trial

Repetitive Transcranial Magnetic Stimulation for Executive Functioning in Veterans with TBI and PTSD: Clinical Outcomes and Connectivity Changes in a Pilot Randomized Clinical Trial

The Lipid Intensive Drug Therapy for Sepsis Phase II Pilot Clinical Trial.

Low cholesterol levels in early sepsis patients are associated with mortality. We sought to test if IV lipid emulsion administration to sepsis patients with low cholesterol levels would prevent a decline or increase total cholesterol levels at 48 hours. Phase II, adaptive, randomized pilot clinical trial powered for 48 patients. Emergency department or ICU of an academic medical center. Sepsis patients (first 24 hr) with Sequential Organ Failure Assessment greater than or equal to 4 or shock. Patients meeting study criteria, including screening total cholesterol levels less than or equal to 100 mg/dL or high-density lipoprotein cholesterol (HDL-C) + low-density lipoprotein cholesterol (LDL-C) less than or equal to 70 mg/dL, were randomized to receive one of three doses of lipid emulsion administered twice in 48 hours or no drug (controls). The primary endpoint was a change in serum total cholesterol (48 hr - enrollment) between groups. Forty-nine patients were enrolled and randomized. Two patients randomized to lipid emulsion were withdrawn before drug administration. Data for 24 control patients and 23 lipid emulsion patients were analyzed. The mean change in total cholesterol from enrollment to 48 hours was not different between groups and was 5 mg/dL (sd 20) for lipid emulsion patients, and 2 mg/dL (sd 18) for control patients (p = 0.62). The mean changes in HDL-C and LDL-C were similar between groups. Mean change in triglycerides was elevated in lipid emulsion patients (61 mg/dL, sd 87) compared with controls (20 mg/dL, sd 70, p = 0.086). The 48-hour change in SOFA score was -2 (interquartile range [IQR] -4, -1) for control patients and -2 (IQR -3, 0) for lipid emulsion patients (p = 0.46). Administration of IV lipid emulsion to early sepsis patients with low cholesterol levels did not influence change in cholesterol levels from enrollment to 48 hours.

Efficacy of povidone-iodine nasal rinse and mouth wash in COVID-19 management: a prospective, randomized pilot clinical trial (povidone-iodine in COVID-19 management)

Objectives/HypothesisTo assess the efficacy of 0.23% povidone-iodine (PVP-I) nasal rinses and mouth washes on detectability of the coronavirus disease 2019 (COVID-19) virus and cycle threshold (Ct) values in nasopharyngeal swabs.Study designThis was an open-label, prospective, randomized, placebo-controlled clinical trial.SettingThe study was conducted in King Saud University Medical City, Riyadh, Saudi Arabia, from August 2021 to July 2022.MethodsParticipants diagnosed with SARS-CoV-2 were randomly assigned to one of three groups, with participants receiving either 0.23% PVP-I, 0.9% normal saline (NS) nasal rinses and mouth washes, or no intervention (control group). Nasopharyngeal swabs were taken 4, 8, 12, and 18 days after the first swab to measure the detectability of the virus and the Ct.ResultsA total of 19 participants were involved in this study. The mean viral survival was 9.8, 12, and 12.6 days for the PVP-I, NS, and control groups, respectively, with a statistically significant difference (p = 0.046). The Ct mean values were 23 ± 3.4, 23.5 ± 6.3, and 26.3 ± 5.9 at the time of recruitment and 25.2 ± 3.5, 15 ± 11.7, and 26.9 ± 6.4 after 4 days for the PVP-I, NS, and control groups, respectively.ConclusionsWhen used continuously at a concentration of 0.23%, PVP-I showed promising results in terms of decreasing the pandemic burden by reducing the period of infectiousness and viral load. However, the use of PVP-I did not result in significantly different changes in the quality-of-life parameters in recently vaccinated and mild COVID-19 patients.

Mobile Medication Adherence Platform for Buprenorphine (MAP4BUP): A Phase I feasibility, usability and efficacy pilot randomized clinical trial

Background/aimPoor medication adherence is one of the main barriers to the long-term efficacy of buprenorphine/naloxone (BUP/NAL). The aims of this pilot investigation were to examine if a Bluetooth-enabled pill cap and mobile application is a feasible, usable tool for increasing BUP/NAL adherence among people with an opioid use disorder. MethodsThis pilot randomized clinical trial (RCT; total n = 41) lasted 12 weeks and was conducted in two office-based BUP/NAL provider locations in Spokane, WA and Coeur d’Alene, ID from January 2020 to September of 2021 with an 11-month gap due to COVID-19. Patients receiving BUP/NAL who consented to participate were randomized to receive the pill cap device (PLY group; n = 19) or a service as usual (SAU group; n = 22) group that included an identical but inactive cap for their bottle. The PLY group received reminders via text and voice, and the support of a “helper” (e.g., friend) to monitor pill cap openings. ResultsMost participants in PLY group found the device both feasible (92.86 %) and usable (78.57 %). Most participants liked using the device (92.86 %) and were satisfied with the device (85.71 %). While not statistically different from one another, medication adherence per the Medication Possession Ratio was 75 % in the SAU group and 84 % in the PLY group. Pill cap openings were significantly higher in the PLY group with an average of 91.8 openings versus the SAU group's average of 56.7 (p < 0.05). ConclusionThe devices was feasible, usable, and patients had high levels of satisfaction. The device was associated with increased pill openings.

Investigating Social Competence in a Pilot Randomized Clinical Trial of a Theatre-Based Intervention Enhanced for Adults with Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is characterized by challenges in social competence that persist in adulthood, yet few treatment options exist. A pilot randomized clinical trial (RCT) of a peer-mediated, theatre-based intervention with established efficacy in youth with ASD was examined in autistic adults. The final sample consisted of forty-seven 18-to-40-year-old participants randomized to the experimental (EXP N = 23) or waitlist control (WLC N = 24) condition. A multimodal, social interdependent model was employed to examine social competence changes in brain (incidental face memory (IFM) using event-related potentials), cognition (Wechsler Memory Scale-III), behavior (Contextual Assessment of Social Skills) and function (Social Responsiveness Scale (SRS); Adaptive Behavior Assessment Scale (ABAS) Social Composite). Using analysis of covariance in which pretest was controlled in the model, posttest between-group differences were observed on IFM (p = 0.016, η2 = 0.139, d = 0.79) and several social and adaptive functional (SRS, ABAS) outcomes in social communication and interaction (SCI) (p = 0.019, η2 = 0.121, d = -00.45), communication (p = 0.044 η2 = 0.09, d = -00.31), and motivation (p = 0.001, η2 = 0.229, d = -0.79) domains. At two-month follow-up, gains in social motivation remained (p = 0.041, η2 = 0.100, d = -0.77). The results offer preliminary support for a unique theatre-based social skills intervention for autistic adults who have few treatment options to enhance social competence. The trial was pre-registered with ClinicalTrials.gov (Identifier: NCT04349644).

Selective digestive tract decontamination to prevent healthcare associated infections in critically ill children: the PICNIC multicentre randomised pilot clinical trial

Healthcare-associated infections (HCAIs) are a major cause of morbidity and mortality in critically ill children. Data from adult studies suggest Selective Decontamination of the Digestive tract (SDD) may reduce the incidence of HCAIs and improve survival. There are no data from randomised clinical trials in the paediatric setting. An open label, parallel group pilot cRCT and mixed-methods perspectives study was conducted in six paediatric intensive care units (PICUs) in England. Participants were children (> 37 weeks corrected gestational age, up to 16 years) requiring mechanical ventilation expected to last for at least 48 h. Sites undertook standard care for a period of 9 weeks and were randomised into 3 sites which continued standard care and 3 where SDD was incorporated into infection control practice for eligible children. Interviews and focus groups were conducted for parents and staff working in PICU. 434 children fulfilled eligibility criteria, of whom 368 (85%) were enrolled. This included 207 in the baseline phase (Period One) and 161 in the intervention period (Period Two). In sites delivering SDD, the majority (98%) of children received at least one dose of SDD and of these, 68% commenced within the first 6 h. Whilst admission swabs were collected in 91% of enrolled children, consent for the collection of additional swabs was low (44%). Recruited children were representative of the wider PICU population. Overall, 3.6 children/site/week were recruited compared with the potential recruitment rate for a definitive cRCT of 3 children/site/week, based on data from all UK PICUs. Parents (n = 65) and staff (n = 44) were supportive of the aims of the study, suggesting adaptations for a larger definitive trial including formulation and administration of SDD paste, approaches to consent and ecology monitoring. Stakeholders identified preferred clinical outcomes, focusing on complications of critical illness and quality-of-life. A definitive cRCT in SDD to prevent HCAIs in critically ill children is feasible but should include adaptations to ecology monitoring along with the dosing schedule and packaging into a paediatric specific format. A definitive study is supported by the findings with adaptations to ecology monitoring and SDD administration.Trial Registration: ISRCTN40310490 Registered 30/10/2020.

High-density transcranial direct current stimulation to improve upper limb motor function following stroke: study protocol for a double-blind randomized clinical trial targeting prefrontal and/or cerebellar cognitive contributions to voluntary motion

BackgroundFocal brain lesions following a stroke of the middle cerebral artery induce large-scale network disarray with a potential to impact multiple cognitive and behavioral domains. Over the last 20 years, non-invasive brain neuromodulation via electrical (tCS) stimulation has shown promise to modulate motor deficits and contribute to recovery. However, weak, inconsistent, or at times heterogeneous outcomes using these techniques have also highlighted the need for novel strategies and the assessment of their efficacy in ad hoc controlled clinical trials.MethodsWe here present a double-blind, sham-controlled, single-center, randomized pilot clinical trial involving participants having suffered a unilateral middle cerebral artery (MCA) stroke resulting in motor paralysis of the contralateral upper limb. Patients will undergo a 10-day regime (5 days a week for 2 consecutive weeks) of a newly designed high-definition transcranial direct current stimulation (HD-tDCS) protocol. Clinical evaluations (e.g., Fugl Meyer, NIHSS), computer-based cognitive assessments (visuo-motor adaptation and AX-CPT attention tasks), and electroencephalography (resting-state and task-evoked EEG) will be carried out at 3 time points: (I) Baseline, (II) Post-tDCS, and (III) Follow-up. The study consists of a four-arm trial comparing the impact on motor recovery of three active anodal tDCS conditions: ipsilesional DLPFC tDCS, contralesional cerebellar tDCS or combined DLPFC + contralesional cerebellar tDCS, and a sham tDCS intervention. The Fugl-Meyer Assessment for the upper extremity (FMA-UE) is selected as the primary outcome measure to quantify motor recovery. In every stimulation session, participants will receive 20 min of high-density tDCS stimulation (HD-tDCS) (up to 0.63 mA/cm2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\mathrm{cm}}^{2}$$\\end{document}) with πcm2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\mathrm{\\pi cm}}^{2}$$\\end{document} electrodes. Electrode scalp positioning relative to the cortical surface (anodes and cathodes) and intensities are based on a biophysical optimization model of current distribution ensuring a 0.25 V/m impact at each of the chosen targets.DiscussionOur trial will gauge the therapeutic potential of accumulative sessions of HD-tDCS to improve upper limb motor and cognitive dysfunctions presented by middle cerebral artery stroke patients. In parallel, we aim at characterizing changes in electroencephalographic (EEG) activity as biomarkers of clinical effects and at identifying potential interactions between tDCS impact and motor performance outcomes. Our work will enrich our mechanistic understanding on prefrontal and cerebellar contributions to motor function and its rehabilitation following brain damage.Trial registrationClinicalTrials.gov NCT05329818. April 15, 2022.

Efficacy of an environmental enrichment intervention for endometriosis: a pilot study.

We have previously shown that Environmental Enrichment (EE), a multi-modal psychosocial intervention consisting of increased social interaction, novelty, and open spaces, improved disease presentation, anxiety, and immune-related disturbances in the rat model of endometriosis. However, there is a knowledge gap regarding the effects of EE interventions in patients with this painful, inflammatory chronic disease. To adapt and test the efficacy of an EE intervention on pelvic pain, mental health, perceived stress, quality of life, and systemic inflammation in endometriosis patients through a randomized clinical trial (RCT). A multidisciplinary team with expertise in physiology, neuroscience, psychology, and women's health adapted and implemented a two-arm RCT comparing an EE intervention with a wait-list control group. Six EE modules administered on alternate weeks were provided to patients in the intervention (N = 29); controls received education only. Survey data and biospecimens were collected at baseline, end-of-study, and 3-months post-intervention to assess pain (Brief Pain Inventory, BPI), endometriosis-related quality of life-QoL (Endometriosis Health Profile-30, EHP30), anxiety (Generalized Anxiety Disorder 7, GAD7), depression (Patient Health Questionnaire for Depression 8, PHQ8), pain catastrophizing (Pain Catastrophizing Score, PCS), stress (Perceived Stress Scale-14, PSS14), and saliva cortisol levels (AM, PM). Compared to the wait-list controls, participants in the EE intervention showed significantly decreased GAD-7 scores at the end of the intervention and 3-month follow-up. Depression, perceived stress, and QoL improved at the 3-month follow-up compared to baseline. While pain levels did not improve, they significantly correlated with anxiety, depression, QoL and pain catastrophizing scores. This pilot RCT demonstrated significant improvements in anxiety and depressive symptoms, QoL, and perceived stress, supporting enriched environments as an integrative psychosocial intervention to be used as adjuvant to the standard of care for endometriosis pain.

The effect of biofeedback pelvic floor training with ACTICORE1 on urinary incontinence: a multicenter randomized clinical pilot trial.

Pelvic floor training with biofeedback has been shown to significantly reduce symptoms of urinary incontinence. The present study aimed to evaluate the effectiveness of pelvic floor training with the ACTICORE1 biofeedback device, which uses a noninsertable pelvic floor sensor with a digital interface. A multicenter randomized controlled clinical pilot study in Germany was conducted between October 2021 and January 2022. The intervention group was instructed to use ACTICORE1 for 6min daily to train the pelvic floor for 12 weeks. The control group was instructed not to do any pelvic floor training. Over 18-year-old men and women with urinary incontinence and an International Consultation on Incontinence Questionnaire score (ICIQ) of ≥5 were included in the study. The primary endpoint was the ICIQ score 12 weeks after enrollment. The secondary endpoints were the ICIQ score and quality of life using the EG-5D-3L questionnaire 4, 8, and 12 weeks after patients' enrollment. A total of 40 individuals with urinary incontinence were recruited for the present study (35 females, 5 males; 40% lost to follow-up). In terms of biometric data, both groups did not differ. At 4, 8, and 12 weeks, the ICIQ scores of those in the ACTICORE1 group decreased from 12.9 to 7.5. The ICIQ score in the control group decreased from 11.0 to 10.5. The intraindividual improvement of patients in the ACTICORE group was statistically significant. Biofeedback training with ACTICORE1 significantly reduces symptoms of urinary incontinence after 12 weeks.

Efficacy of BREATHOX® Device Inhalation on Acute Symptoms Associated with COVID-19 (BREATH Study): A Randomized Pilot Clinical Trial.

(1) Background: A high concentration of sodium chloride on in vitro cell culture leads to reduced SARS-CoV-2 replication. Therefore, our aim was to evaluate the effects of inhaling hypertonic NaCl particles (BREATHOX®) on the duration of COVID-19-induced acute symptoms. (2) Methods: A prospective, open label, randomized, standard of care-controlled group (SOC) pilot trial compared inhaled oral and nasal administered BREATHOX® (2.0 mg NaCl, particles size between 1-10 μm), with five or ten inhalations per day for ten days. The primary endpoint was the time to resolve COVID-19-related symptoms. Safety outcomes included adverse clinical and laboratory events. (3) Results: A total of 101 individuals were screened and 98 were randomly assigned to BREATHOX® ten sessions per day (Group 1; 33 patients), BREATHOX® five sessions per day (Group 2; 32 patients), or SOC (33 patients), and followed up for 28 days. There was an association with cough frequency after 10 days BREATHOX® compared to SOC [Group 1: hazard ratio (HR) 2.01, 95% confidence interval (CI) 1.06-3.81; Group 2: HR 2.17, 95% CI 1.17-4.04]. No differences between the groups for the reported symptoms' resolution time were seen after 28 days. After combining both BREATHOX® groups, the period to cough resolution 10 days after randomization was significantly lower than in SOC (HR 2.10, 95% CI 1.20-3.67). An adverse event occurred in 30% of Group 1, 36% of Group 2, and 9% in SOC individuals. One patient from SOC had a serious adverse event. Nasal burning, sore or itchy nose, and dry mouth were considered related to BREATHOX® use and resolved after stopping inhalations. (4) Conclusion: BREATHOX® inhalation is safe and may be effective in reducing the duration of COVID-19-induced coughing.

Metacognitive interpersonal therapy-eating disorders versus cognitive behavioral therapy for eating disorders for non-underweight adults with eating disorders: study protocol for a pilot pre-registered randomized controlled trial.

Eating disorders (ED) are serious disorders characterized by an alteration of eating habits and excessive concern about weight and body shapes (Fairburn, 2002), accompanied by significant impairment inequality of life, high mortality rates and serious organic consequences (Jenkins et al., 2011; Treasure et al., 2015; 2020). Although evidence-based psychological therapies for nonunderweight ED presentations such as cognitive behavioral therapy for eating disorders (CBT-ED) are widely available, there is substantial scope for improvements, particularly in terms of efficacy and adherence. One option is to develop interventions to address elements of pathology not fully addressed by existing empirical supported treatments, such as incorporating techniques aimed at addressing interpersonal problems and personality disorder features into existing treatment delivery. We adapted Metacognitive Interpersonal Therapy, a psychological intervention supported by evidence for treating personality disorders and integrated it with existing CBT techniques for eating disorders (MIT-ED). MIT-ED targets aspects of ED that are not included in the transdiagnostic CBT-E model such as poor metacognition, or maladaptive interpersonal schemas. This is a pre-registered (Protocol number: 0000781) pilot randomized clinical trial aimed at assessing acceptability and feasibility of MIT-ED and establishing preliminary evidence of effectiveness for future larger studies. Twenty patients (10 in each arm) will be randomized to 20 sessions of individual psychotherapy, either MIT-ED or CBTE. Repeated follow-ups will be collected up to 24 months. Participants are recruited at a private outpatient clinic for ED treatment. Acceptability will be assessed via session attendance, completion rates and preliminary outcomes. The primary outcome is ED pathology assessed with the Eating Disorder Examination Questionnaire-6. Other ED outcomes assessed will be eating disorder attitudes, clinical impairment and binge eating pathology. Secondary treatment outcomes are anxiety, depression, and global symptomatology. We will also assess emotional awareness, emotion regulation and therapeutic alliance. Based on previous studies of MIT for personality disorders we hypothesize that MIT-ED will be acceptable to patients, evidenced by high treatment adherence and retention. We hypothesize that MIT-ED will be associated with reductions in eating disorder pathology, at least equivalent to CBT-E. Results will be used to inform the study design, sampling, likely effect sizes and choice of outcome measures for future larger trials of MIT-ED in ED samples.

Efficacy of interactive manual dexterity training after stroke: a pilot single-blinded randomized controlled trial

ObjectiveTo compare the efficacy of Dextrain Manipulandum™ training of dexterity components such as force control and independent finger movements, to dose-matched conventional therapy (CT) post-stroke.MethodsA prospective, single-blind, pilot randomized clinical trial was conducted. Chronic-phase post-stroke patients with mild-to-moderate dexterity impairment (Box and Block Test (BBT) > 1) received 12 sessions of Dextrain or CT. Blinded measures were obtained before and after training and at 3-months follow-up. Primary outcome was BBT-change (after–before training). Secondary outcomes included changes in motor impairments, activity limitations and dexterity components. Corticospinal excitability and short intracortical inhibition (SICI) were measured using transcranial magnetic stimulation.ResultsBBT-change after training did not differ between the Dextrain (N = 21) vs CT group (N = 21) (median [IQR] = 5[2–7] vs 4[2–7], respectively; P = 0.36). Gains in BBT were maintained at the 3-month post-training follow-up, with a non-significant trend for enhanced BBT-change in the Dextrain group (median [IQR] = 3[− 1–7.0], P = 0.06). Several secondary outcomes showed significantly larger changes in the Dextrain group: finger tracking precision (mean ± SD = 0.3 ± 0.3N vs − 0.1 ± 0.33N; P < 0.0018), independent finger movements (34.7 ± 25.1 ms vs 7.7 ± 18.5 ms, P = 0.02) and maximal finger tapping speed (8.4 ± 7.1 vs 4.5 ± 4.9, P = 0.045). At follow-up, Dextrain group showed significantly greater improvement in Motor Activity Log (median/IQR = 0.7/0.2–0.8 vs 0.2/0.1–0.6, P = 0.05). Across both groups SICI increased in patients with greater BBT-change (Rho = 0.80, P = 0.006). Comparing Dextrain subgroups with maximal grip force higher/lower than median (61.2%), BBT-change was significantly larger in patients with low vs high grip force (7.5 ± 5.6 vs 2.9 ± 2.8; respectively, P = 0.015).ConclusionsAlthough immediate improvements in gross dexterity post-stroke did not significantly differ between Dextrain training and CT, our findings suggest that Dextrain enhances recovery of several dexterity components and reported hand-use, particularly when motor impairment is moderate (low initial grip force). Findings need to be confirmed in a larger trial.Trial registration ClinicalTrials.gov NCT03934073 (retrospectively registered)

Acceptability of a Hypothetical Reduction in Routinely Scheduled Clinic Visits Among Patients With History of a Localized Melanoma (MEL-SELF): Pilot Randomized Clinical Trial.

After treatment for a localized melanoma, patients attend routinely scheduled clinics to monitor for new primary or recurrent melanoma. Patient-led surveillance (skin self-examination with patient-performed teledermoscopy) is an alternative model of follow-up that could replace some routinely scheduled visits. This study aims to assess the acceptability of a hypothetical reduction in routinely scheduled visits among participants of the Melanoma Self Surveillance (MEL-SELF) pilot randomized clinical trial of patient-led surveillance (intervention) versus usual care (control). Patients previously treated for localized melanoma in New South Wales who were participating in the MEL-SELF pilot randomized clinical trial were asked to respond to a web-based questionnaire at baseline and after 6 months on trial. We used mixed methods to analyze the data. The main outcome of interest was the acceptability of a hypothetical reduction in routinely scheduled visits for melanoma surveillance. Of 100 randomized participants, 87 answered the questionnaire at baseline, 66 answered the questionnaire at 6 months, and 79 provided a free-text explanation at either time point. At 6 months, 33% (17/51) of the control group and 35% (17/49) of the intervention group indicated that a hypothetical reduction in routinely scheduled visits with all melanoma doctors was at least slightly acceptable (difference in proportions -1%, 95% CI -20% to 17%; P=.89). Participants suggested that prerequisites for a reduction in routinely scheduled visits would include that sufficient time had elapsed since the previous diagnosis without a new primary melanoma or recurrence, an unscheduled appointment could be made at short notice if the patient noticed something concerning, their melanoma doctor had suggested reducing their clinic visit frequency, and patients had confidence that patient-led surveillance was a safe and effective alternative. Participants suggested that a reduction in routinely scheduled visits would not be acceptable where they perceived a very high risk of new or recurrent melanoma, low self-efficacy in skin self-examination and in the use of technologies for the patient-led surveillance intervention, and where they had a preference for clinician-led surveillance. Some patients said that a partial reduction to once a year may be acceptable. Some patients may be receptive to a reduction in routinely scheduled visits if they are assured that patient-led surveillance is safe and effective. Australian New Zealand Clinical Trials Registry ACTRN12616001716459; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371865&isReview=true; ClinicalTrials.gov NCT03581188; https://clinicaltrials.gov/ct2/show/NCT03581188. RR2-10.1001/jamadermatol.2021.4704.

Management of Anxiety in Coronary Artery Bypass Grafting Patients: The Influence of Chair Aerobics and Nadisodhana Pranayama-A Pilot Randomized Clinical Trial

Abstract: Background: Anxiety is a primary concern affecting the prognosis of CABG patients. Relieving anxiety is thus a component of management in patients with CABG. We use two feasible and cost-effective treatment techniques to know the improvement in symptoms of anxiety. Objectives: To evaluate the efficacy of chair aerobics and pranayama on anxiety in patients who underwent CABG. We hypothesized that there would be an improvement in anxiety in CABG patients after receiving the interventions. Materials and Methods: In a total of 21 screened, 16 met eligibility requirements. These were randomized into two, group A and group B. Group A is treated with progressive chair aerobics, and group B with Nadi-sodhana pranayama. Both groups were given standardised cardiac rehabilitation techniques. The duration was fifteen minutes of activity along with phase 1 cardiac rehabilitation. The treatment session was given once a day in the morning. The intervention starts from the post-operative day 3 to post-operative day 7. The anxiety is measured by the tool “hospital anxiety and depression scale”. Heart rate is estimated to know the somatic and physiologic components of anxiety. Took all the outcome measures before the surgery and on post-operative day 7 by a blinded outcome assessor. Results: The results showed that the improvement in the p-value of HADS anxiety, depression, and heart rate of both groups is less than 0.05. Keywords: Coronary Artery Bypass, Anxiety, Nadi-sodhana Pranayama, Chair aerobics, Cardiac rehabilitation.

Remotely supervised at-home tDCS for veterans with persistent post-traumatic headache: a double-blind, sham-controlled randomized pilot clinical trial.

Currently, there are no FDA approved therapies for persistent post-traumatic headache (PPTH) secondary to traumatic brain injury (TBI). As such neither headache nor TBI specialists have an effective means to manage PPTH. Thus, the objective of the present pilot trial was to evaluate the feasibility and preliminary efficacy of a four-week at-home remotely supervised transcranial direct current stimulation (RS-tDCS) intervention for veterans with PPTH. Twenty-five (m = 46.6 ± 8.7 years) veterans with PPTH were randomized into two groups and received either active (n = 12) or sham (n = 13) RS-tDCS, with anodal stimulation over left dlPFC and cathodal over occipital pole. Following a four-week baseline, participants completed 20-sessions of active or sham RS-tDCS with real-time video monitoring over a period of four-weeks. Participants were assessed again at the end of the intervention and at four-weeks post-intervention. Primary outcomes were overall adherence rate (feasibility) and change in moderate-to-severe headache days per month (efficacy). Secondary outcomes were changes in total number of headache days, and PPTH-related functional outcomes. Adherence rate was high with 88% of participants (active = 10/12; sham = 12/13) fully completing tDCS interventions. Importantly, there was no significant difference in adherence between active and sham groups (p = 0.59). Moderate-to-severe headache days were significantly reduced within the active RS-tDCS group (p = 0.004), compared to sham during treatment (-2.5 ± 3.5 vs. 2.3 ± 3.4), and 4-week follow-up (-3.9 ± 6.4 vs. 1.2 ± 6.5). Total number of headache days was significantly reduced within the active RS-tDCS (p = 0.03), compared to sham during-treatment (-4.0 ± 5.2 vs. 1.5 ± 3.8), and 4-week follow-up (-2.1 ± 7.2 vs. -0.2 ± 4.4). The current results indicate our RS-tDCS paradigm provides a safe and effective means for reducing the severity and number of headache days in veterans with PPTH. High treatment adherence rate and the remote nature of our paradigm indicate RS-tDCS may be a feasible means to reduce PPTH, especially for veterans with limited access to medical facilities.Clinical Trial Registration: ClinicalTrials.gov, identifier [NCT04012853].

Feasibility and acceptability of online opioid overdose education and naloxone distribution: Study protocol and preliminary results from a randomized pilot clinical trial

Drug overdose is the leading cause of accidental death in the United States, with over 70% of drug related fatalities resulting from the use of opioids. Federal agencies have responded to this crisis with various recommendations including enhancing harm reduction approaches such as training laypersons to administer naloxone through Opioid Overdose Education and Naloxone Distribution (OEND) programs. Several studies have demonstrated that OEND programs effectively reduce opioid overdose mortality and are both safe and cost-effective, however, they are typically implemented in urban areas as part of large medical center research programs, needle exchanges, or drug treatment programs. Individuals living in areas without these programs or services lack access to critical and life-saving OEND. The current study examined the acceptability and feasibility of online recruitment, online opioid overdose education, and remote distribution of naloxone kits. Persons who illicitly use opioids and are at risk for overdose were recruited through online media and completed an opioid use questionnaire. If interested in receiving opioid overdose and naloxone administration training, participants completed pre- and post-intervention knowledge questionnaires, engaged in audiovisual training, and were randomized to either receive a naloxone kit or be given information on where they could obtain one. Preliminary results indicate feasibility and acceptability as evidenced by strong recruitment and retention, as well as high participant satisfaction ratings. Successful implementation of remote OEND through this project supports future employment of similar remote programs to expand this critical harm reduction strategy to high-risk individuals in areas lacking traditional OEND programs. Trial Registration #Clinitaltrials.gov- NCT04303000.

385 Combining Cannabidiol with Prolonged Exposure Therapy for PTSD: Design and Methodology of a Pilot Randomized Clinical Trial

OBJECTIVES/GOALS: There is increasing evidence that cannabidiol (CBD) has promising potential to treat PTSD. However, more research is warranted to fully understand the benefits of CBD for PTSD. This poster will describe the design and methodology of one of the first ever pilot RCTs examining CBD (vs. placebo) combined with prolonged exposure therapy for PTSD. METHODS/STUDY POPULATION: This study is an early Phase II double-blind, pilot RCT. Participants are 24 individuals 18-65 years old who meet DSM-5 criteria for PTSD on the CAPS-5 and were recruited from local hospitals and the community. Individuals complete a standardized baseline assessment with an independent evaluator to assess study eligibility. Participants who meet study inclusion are randomized to 18 days of CBD 250mg (BID) or placebo delivered in combination with 10-sessions Prolonged Exposure (PE) psychotherapy over 2 weeks. Individuals begin medication 3 days prior to beginning PE to ensure steady state. Participants complete self-report and biomarker outcomes at select timepoints during study participation, and are also asked to complete a 1-month follow-up assessment following treatment. RESULTS/ANTICIPATED RESULTS: This aims of this study are to: 1) examine the safety, feasibility, and PTSD symptom reductions associated with the combined intervention; 2) evaluate biomarkers associated with the endocannabinoid system and stress response; 3) determine the association between changes in biomarkers and PTSD symptoms following treatment. It is expected that CBD+PE will be safe and feasible, and that there will be a detectable signal of CBD vs. placebo in the reduction of PTSD symptoms. It is also anticipated that CBD will have higher levels of endocannabinoids and lower stress response levels compared to placebo. Lastly, we expect that greater changes in biomarkers will be associated with lower levels of PTSD severity following treatment. DISCUSSION/SIGNIFICANCE: Although there is growing interest in cannabinoids for psychiatric conditions, such as PTSD, controlled trials are limited and have yet to examine the proposed intervention for PTSD. If successful, this study will enhance the feasibility of a larger, adequately powered RCT to address immediate and long-term improvements for PTSD treatments.

The effect of cognitive behavioral therapy on future thinking in patients with major depressive disorder: A randomized controlled trial.

Pessimistic thinking about the future is one of the cardinal symptoms of major depression. Few studies have assessed changes in pessimistic thinking after undergoing cognitive behavioral therapy (CBT). A randomized clinical trial (RCT) was conducted with patients diagnosed with major depressive disorder (MDD) to determine whether receiving a course of CBT affects pessimistic future thinking using a future thinking task. Thirty-one patients with MDD were randomly assigned to either CBT (n = 16) or a talking control (TC) (n = 15) for a 16-week intervention. The main outcomes were the change in response time (RT) and the ratio of the responses for positive valence, measured by the future thinking task. Secondary outcomes included the GRID-Hamilton Depression Rating Scale, the Beck Depression Inventory-Second Edition (BDI-II), the Dysfunctional Attitude Scale (DAS), and the word fluency test (WFT). Regarding the main outcomes, the CBT group showed reduced RT for the positive valence (within-group Cohen's d = 0.7, p = 0.012) and negative valence (within-group Cohen's d = 0.6, p = 0.03) in the distant future condition. The ratio of positive valence responses in both groups for all temporal conditions except for the distant past condition increased within group (distant future: CBT: Cohen's d = 0.5, p = 0.04; TC: Cohen's d = 0.8, p = 0.008; near future: CBT: Cohen's d = 1.0, p < 0.001; TC: Cohen's d = 1.1, p = 0.001; near past: CBT: Cohen's d = 0.8, p = 0.005; TC: Cohen's d = 1.0, p = 0.002). As for secondary outcomes, the CBT group showed greater improvement than the TC group regarding the need for social approval as measured by the DAS (p = 0.012). Patients with MDD who received CBT showed a reduced RT for the positive and negative valence in the distant future condition. RT in the future thinking task for depressed patients may be a potential objective measure for the CBT treatment process. Because the present RCT is positioned as a pilot RCT, a confirmatory trial with a larger number of patients is warranted to elucidate the CBT treatment process that influences future thinking. https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000021028, identifier UMIN000018155.

Physiotherapeutic treatment associated with the pain neuroscience education for patients with chronic non-specific low back pain-single-blind randomized pilot clinical trial.

Pain Neuroscience Education (PNE) shows improvement in pain and functional capacity in patients with chronic low back pain (CLBP). Therefore, the study aimed to verify if the physiotherapeutic treatment associated with PNE decreases the functional disability of patients with nonspecific CLBP. Forty patients were clinically evaluated and answered the following questionnaires: Brief pain inventory, Central Sensitization Inventory (CSI), Roland-Morris disability questionnaire, pain catastrophizing scale, Tampa scale of kinesiophobia, hospital anxiety, and depression scale, SF6D quality of life questionnaire and performed quantitative sensory tests (QSTs). Afterward, they were randomly divided into the intervention group (IG, n=20) and the control group (CG, n=20). Both performed kinesiotherapy exercises twice a week for 6 weeks. The IG received 3 individual PNE sessions and answered the pain neurophysiology questionnaire. IG showed significant improvement for all variables analyzed (p<0.001). The association decreased the kinesiophobia (estimated difference between CG-IG means: 7.6-95% CI: 2.3-12.9) (p=0.006). In the lumbar paravertebral region (CG and IG), there was a statistical difference in the intensity of CLBP in the QSTs (p<0.05). The association showed better results compared to only therapeutic exercises to reduce kinesiophobia and change the perception of pain intensity in the lumbar region.