Tag: Clinical trial

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Barriers and Facilitators in the Implementation of the Systematic Medical Appraisal, Referral, and Treatment (SMART) Mental Health Digital Intervention in Rural India: Mixed Methods Process Evaluation Study

<strong>Background:</strong> An estimated 150 million people have mental health care needs in India, but only 15% are able to access care. Depression and anxiety contribute to a large proportion of mental morbidity. The Systematic Medical Appraisal, Referral, and Treatment (SMART) Mental Health trial used a mobile-based clinical decision support system for primary care doctors and community health workers (CHWs) to identify and treat people at risk of depression, anxiety disorders, and self-harm. A community-based antistigma campaign was also delivered. The intervention led to improved remission rates for depression and anxiety and lower stigma scores. <strong>Objective:</strong> A process evaluation assessed (1) implementation fidelity, barriers, and facilitators; (2) perceptions of doctors and CHWs on the use of SMART Mental Health; and (3) the causal pathways that led to trial outcomes. <strong>Methods:</strong> A mixed methods evaluation combining backend program data and qualitative data was conducted. A total of 38 focus group discussions and 37 key informant interviews were conducted with primary doctors, CHWs, government officials, local community leaders, and research project staff. The data were coded and analyzed using a framework analysis approach based on the UK Medical Research Council guidance on process evaluations and the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. <strong>Results:</strong> The intervention had high implementation fidelity. Across clusters, the median proportion of participants with at least 1 CHW follow-up was 98% (IQR 96.6%-100%). The referral rate for a psychiatrist was low (224/1697, 13.2%), and only 23.6% (53/224) of those referred visited the psychiatrist. The median exposure to antistigma audiovisual content was 84% (IQR 65.7%-95.9%). At the community level, key implementation barriers included cultural inhibitions in seeking mental health care and the unavailability of patients due to competing demands. Proximity and tight social connections between CHWs and their communities were important facilitators in seeking medical help. Doctor and CHW training, mentoring, and feedback provided by program staff were important facilitators to support the use of the digital health components by the health workforce. <strong>Conclusions:</strong> A complex intervention that included both community-based antistigma and clinical digital health interventions achieved high implementation fidelity. Key areas to consider for maintenance of such interventions include (1) the need for sustained community-based strategies to address stigma and other cultural barriers; (2) health workforce strengthening policies, including supportive supervision for CHWs and doctors to increase capability in the use of mental health digital health tools; and (3) strategies to improve access to specialist care for those with more complex care needs. <strong>Trial Registration:</strong> Clinical Trial Registry India CTRI/2018/08/015355; https://tinyurl.com/5r63suxp
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STAT+: Cytokinetics drug Myqorzo meets twin efficacy goals in study of genetic heart disease

Cytokinetics said Tuesday that its drug Myqorzo significantly improved heart failure symptoms and cardiovascular fitness in patients with non-obstructive hypertrophic cardiomyopathy, an inherited heart disorder. 

The results, reported in a company press release, achieved the dual efficacy goals of a Phase 3 clinical trial, called ACACIA, with statistical significance.

Cytokinetics is in the early days of Myqorzo’s commercial launch as a treatment for the more severe “obstructive” form of hypertrophic cardiomyopathy, or HCM. The successful outcome of the ACACIA study, if also cleared by regulators, could greatly expand the number of HCM patients eligible for treatment — and boost the drug’s peak sales to $5 billion annually, according to analyst forecasts. 

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Usability, Acceptability, and Feasibility of a Personalized Adaptive Mirror Therapy for Upper-Limb Poststroke Rehabilitation Using Immersive Virtual Reality and Myoelectric Control: Single-Arm Pre-Post Study

<strong>Background:</strong> Stroke remains a primary cause of long-term disability worldwide, with upper-limb deficits affecting up to 80% of survivors acutely and 40% chronically. These deficits lead to considerable effects on their independence and overall quality of life. Conventional rehabilitation therapies are most effective when initiated shortly after a stroke, yet many patients face barriers to ongoing therapy post discharge. Recent advancements in low-cost rehabilitation systems, particularly those using virtual reality (VR) technologies, offer promising alternatives for enhancing upper-limb recovery. <strong>Objective:</strong> Given the burden on health care systems and the limitations in access to high-intensity postdischarge rehabilitation, this study aimed to evaluate the feasibility, acceptability, and usability of an upper-limb adaptive mirror therapy using VR and myoelectric control for the rehabilitation of patients with chronic stroke developed through a user-centered design approach. <strong>Methods:</strong> In this study, a total of 12 community-dwelling survivors of chronic stroke (mean age 52.9, SD 16.0 years; 4 female) with moderate to severe upper-limb impairments were enrolled. Participants were stratified by age (young: 18-55 years; older: 56-80 years) and impairment level (Fugl-Meyer Assessment-Upper Extremity score: 18-36=severe; 37-54=moderate). Acceptability was assessed for each session by patient self-evaluation of satisfaction and motivation through a visual analog scale, while the therapist assessed the patient’s participation in therapy using the Pittsburgh Participation Rehabilitation Scale. Usability was measured with the User Satisfaction Evaluation Questionnaire scale and feasibility through the NASA (National Aeronautics and Space Administration) Task Load Index cognitive workload indices. <strong>Results:</strong> Patients reported a significant increase in satisfaction from the intermediate to the final assessment (T1: 72% vs T2: 85%; <i>P</i>=.01) and stable high motivation levels. Differences in participation and motivation were observed based on impairment levels, with no effect of age. Usability ratings remained high (&gt;80%) throughout the intervention, with no significant differences between baseline and end line (<i>P</i>=.56). Cognitive workload assessments showed a significant reduction over time, in perceived cognitive (<i>P</i>=.04), performance (<i>P</i>=.007), and effort demands (<i>P</i>&lt;.001). Impairment level significantly influenced perceived workload, with participants with more severe impairment reporting higher cognitive, physical, temporal, and effort demands (all <i>P</i>&lt;.001), while age did not contribute to variability in acceptability, usability, or workload measures. <strong>Conclusions:</strong> VR therapy was found to be feasible, under adaptive task conditions, ensuring stable performance across patients. The protocol was usable and acceptable among patients with chronic stroke, especially those with moderate impairment, supporting its potential as a user-centered digital rehabilitation tool, warranting further investigation in controlled and home-based settings. <strong>Trial Registration:</strong> ClinicalTrials.gov NCT07103122; https://clinicaltrials.gov/study/NCT07103122
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STAT+: Biotech raises $42 million to run Huntington’s disease trial

Gene therapy startup Latus Bio has raised another $42 million to start its first clinical trials, where it will try to sidestep issues that have set back a more advanced competitor. 

Latus is moving two treatments through clinical trials this year. The first is for a form of Batten disease called CLN2 disease, a fatal genetic condition that causes seizures, vision loss, and cognitive problems. The company anticipates having initial clinical data by the end of the year. 

Now, Latus — founded by Beverly Davidson, chief scientific strategy officer at the Children’s Hospital of Philadelphia — is turning its attention to a second drug candidate, a gene therapy for Huntington’s disease.

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A Bilingual AI-Based Chatbot for Nutrition Education in a Food Is Medicine Intervention for High-Risk Pregnant Women: Design and Development Study

Background: Conversational agents (artificial intelligence [AI]–based chatbots) offer a novel approach to health interventions by providing personalized, adaptive interactions that improve over time based on user engagement. In nutrition education, given the wide variation in knowledge, skills, and abilities across participants, AI-based chatbots have the potential to enhance accessibility, engagement, and behavior change. Food is Medicine (FIM) interventions, which aim to improve food security and diet quality among multicultural, at-risk populations, often face challenges related to sustained engagement and use. Objective: This paper describes the design, development, and iterative refinement of a bilingual AI-driven nutrition chatbot integrated into an FIM intervention for high-risk pregnant women receiving care at obstetric clinics in Houston, Texas. Methods: The chatbot was developed using an iterative process informed by behavioral theory, human-centered design (HCD), and plan-do-study-act (PDSA) quality improvement cycles. The conversational agent was embedded within an ongoing 2-arm randomized controlled trial (N=200) comparing standard FIM nutrition education to FIM plus AI-driven nutrition chatbot support. HCD activities took place prior to deployment and involved community advisory group members and implementation stakeholders. Postdeployment refinements were guided by 2 PDSA cycles and informal question-and-answer sessions conducted with intervention arm participants. Qualitative feedback was collected using structured scripts to identify facilitators of and barriers to chatbot engagement. Results: The chatbot was developed using the GPT-3.5 Turbo application programming interface. An initial prototype built in Python using Gradio enabled rapid testing but lacked flexibility for modifications. To improve scalability and logging capabilities, the system was rebuilt using PHP, HTML, JavaScript, and SQL. To further understand usage patterns, participants who interacted with the chatbot at least once or not at all (classified as low users; n=32) were engaged in question-and-answer sessions. Of these participants, all were female (32/32, 100%), 88% (28/32) identified as Hispanic or Latino, and 90% (29/32) preferred Spanish. Two PDSA cycles guided iterative refinements. Cycle 1 identified low initial engagement, whereas cycle 2 focused on improving content clarity and cultural relevance through physical reminder prompts. Qualitative findings identified key barriers to engagement, including high cooking self-efficacy with perceived lack of need for support, low technology self-efficacy, and low urgency due to competing priorities. Conclusions: Embedding a bilingual AI-driven nutrition chatbot within an FIM intervention was feasible and featured critical design and implementation considerations for engaging high-risk pregnant populations. Findings show the importance of HCD and iterative refinement to address engagement barriers. This work provides actionable guidance for integrating conversational agents into FIM programs, with implications for future evaluation of clinical outcomes, long-term engagement, and scalability. Trial Registration: ClinicalTrials.gov NCT07165990; https://clinicaltrials.gov/study/NCT07165990
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OTX-202 Smartphone App to Reduce Suicidal Ideation Among High-Risk Transition-Age Youth: Open-Label, Single-Arm, Phase 1 Clinical Trial

<strong>Background:</strong> The transition from adolescence to adulthood (18 to 25 years) is associated with an increased risk of suicidal ideation and behaviors. Suicide-focused cognitive behavioral therapies (CBTs) have been shown to significantly reduce suicidal ideation and behaviors but are not widely available to high-risk individuals. Digital therapeutics could improve access to these treatments. <strong>Objective:</strong> This study aimed to evaluate the acceptability, safety, and potential efficacy of OTX-202 among transition-age youth (18 to 25 years) receiving mental health care outside an inpatient hospital setting. <strong>Methods:</strong> In this phase 1 single-arm clinical trial, 59 transition-age youth with recent suicidal ideation or suicide attempts used OTX-202, a smartphone app designed to deliver suicide-focused CBT, concurrently with usual outpatient mental health care. After baseline, eligible patients completed 12 weekly assessments of suicidal ideation, depression, and anxiety. <strong>Results:</strong> From baseline to week 12, participants reported statistically significant, large reductions in suicidal ideation (mean difference –5.1, 95% CI –6.5 to –3.7; <i>d</i>=0.95). In total, 3 (5.1%; 95% CI 0%-11.2%) participants reported suicide attempts. Reductions in suicidal ideation and suicide attempt rates were consistent with results from previously published randomized clinical trials of suicide-focused CBTs. Participants rated OTX-202 in the 97th percentile of usability and completed a mean of 9.0 (SD 3.5) of 12 app modules, supporting the app’s acceptability. There were no patient deaths, device-related events, or severe adverse events, supporting the app’s safety. <strong>Conclusions:</strong> Results support the safety, acceptability, and potential efficacy of OTX-202 for reducing suicide risk among transition-age youth. <strong>Trial Registration:</strong> ClinicalTrials.gov NCT06008132; https://clinicaltrials.gov/study/NCT06008132
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Effects of bifrontal-transcranial direct current stimulation combined with music listening on sleep quality, cortical activation and functional connectivity in patients with insomnia: a randomised controlled trial by fNIRS

BackgroundAlthough music listening and transcranial direct current stimulation (tDCS) alone have certain effects in the treatment of insomnia, the sleep regulatory effects and neural mechanisms of the combined treatment in patients with insomnia disorder (ID) are unclear. This study aimed to investigate the efficacy of combined bifrontal-tDCS (F3: anode, F4: cathode) with music listening in patients with ID using functional near-infrared spectroscopy (fNIRS).Methods76 ID patients were randomly divided into an intervention group (n=38) and a control group (n=38), and received 4 weeks of a total of 20 sessions of music + tDCS therapy and music + sham tDCS therapy (30-second stimulation with fade-in/fade-out to mimic somatic sensations), respectively. The Pittsburgh Sleep Quality Index Scale (PSQI), Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), and Perceived Stress Scale (PSS-14) were compared between the two groups before and after treatment. Oxy-haemoglobin (HbO2) concentration and functional connectivity (FC) were assessed during the verbal fluency task using fNIRS.ResultsCompared with the control group, the PSQI total score (mean difference: -2.57 points, 95% CI: -4.43 to -0.71, p = 0.001), PSQI sub-scores except “sleep disturbance and daytime dysfunction”, SDS and SAS scores of the intervention group improved significantly after treatment. It was observed by fNIRS that the HbO2 concentration in the medial prefrontal cortex (mPFC), left dorsolateral prefrontal cortex (DLPFC), right ventrolateral prefrontal cortex, and right superior frontal cortex (SFC) increased significantly after treatment in the intervention group but was not superior to the control group. In addition, the FC enhancement of left SFC-left DLPFC and left SFC-mPFC after treatment was significantly better in the intervention group than in the control group, and the PSQI improvement was positively correlated with the FC enhancement of channel-averaged and left SFC-right DLPFC.ConclusionsCombining bifrontal-tDCS with music listening is more helpful in improving sleep quality and prefrontal functional connectivity in ID patients compared with music listening alone. For ID patients, music electrical stimulation headphones may be a safe, effective, and convenient new treatment strategy.Clinical trial registrationhttps://www.chictr.org.cn/, identifier ChiCTR2400086233.