Long-term follow-up of clinical trial participants: Predictors of post-trial response in older subjects.

BACKGROUND AND OBJECTIVE: The post-trial follow-up (PTFU) phase of a clinical trial can provide important information on maintenance of intervention effects. However, approaches for the PTFU are rarely described. This short communication describes our process for PTFU that involved recontacting older subjects who participated in a clinical trial between 2015 and 2019. We also describe correlates of response to our PTFU survey. METHODS: The parent clinical trial aimed to reduce depression symptoms among older spousally-bereaved adults. We attempted to recontact our sample during the early stages of the COVID-19 pandemic. Using logistic regression, we examined physical health, depression symptoms, cognitive status, and disability as correlates of participant response to the PTFU phase. RESULTS: Forty-two percent of participants responded to the PTFU survey. Disability - or the inability to participate in major life tasks and social roles - was significantly associated with response. Participants with greater disability were less likely to respond to the PTFU survey. CONCLUSIONS: Older adults with disabilities may need alternative and supportive strategies for engaging in the PTFU phase. CLINICAL TRIALS REGISTRATION: NCT02631291.

Incorporating technology in research with older bereaved adults: Lessons learned from conducting an internet-based randomized controlled trial.

Objective: Digital health interventions (DHI) involve multiple interactions between the user, technology platform, and study team, posing challenges for implementation. This paper describes the lessons learned while implementing an internet-based randomized controlled trial (RCT) for reducing depression symptom burden in older acutely-bereaved adults. Methods: The RCT was entitled "Widowed Elders' Lifestyle after Loss" (or WELL), which compared the efficacy of a DHI to an enhanced usual care (EUC) for reducing depression symptoms in adults 60+ years who lost their spouse/life partner within the previous 12 months. Participants randomized to the DHI used their own tablet, smartphone, or pc to record the timing and regularity of sleep, meals, and physical activity twice daily, for 12 weeks. The also received weekly health coaching sessions from a clinician certified in motivational interviewing. Participants randomized to the EUC arm received weekly calls from research staff and were assessed on the same schedule as intervention participants. All study procedures were conducted virtually. Methodological and procedural challenges were discussed weekly with study staff and the primary investigator. Results: Many challenges can be categorized as follows recruiting virtually, obtaining informed consent, training older adults to use technology, and establishing rapport with older adults. Solutions required researcher and interventionist flexibility in adapting to new strategies. For instance, we redesigned the informed consent process to include a user-friendly brochure that enhanced participants' understanding of the RCT and improved our enrollment rate. We also utilized user-engagement in refining an intervention protocol. Conclusion: We resolved implementation challenges without compromising internal validity via interdisciplinary collaborations with mobile programmers to ensure our technology met the unique and varied needs of aging users. The solutions from this study may promote the recruitment and retainment of older adults in research studies that use technology-based interventions.

A digital health intervention to stabilize the 24-hour rhythm of sleep, meals, and physical activity for reducing depression among older bereaved spouses: Protocol for a randomized controlled trial.

BACKGROUND: Despite the high prevalence of depression and disruption to 24-h sleep-wake routines following the death of a spouse in late-life, no bereavement interventions have been developed to re-entrain a regular sleep-wake routine among older widow(er)s. We describe the rationale and methodology of the NIH-funded WELL Study (Widowed Elders' Lifestyle after Loss), a randomized controlled trial (RCT) comparing the efficacy of a digital health intervention (DHI) to enhanced usual care (EUC) arm for reducing depression symptoms in older spousally-bereaved adults. METHODS: We will randomize approximately 200 recently bereaved (<12 months) adults aged 60+ years to one of two 12-week interventions: digital monitoring of the timing and regularity of sleep, meals, and physical activity plus weekly motivational health coaching; or enhanced usual care consisting of weekly telephone calls and similar assessment schedules. Participants will complete self-report and clinical assessments at baseline, post-intervention, and 3-, 6-, and 12-months post-intervention, and objective actigraphic assessments of their 24-h rest-activity rhythm (RAR) at baseline and 1-, 2-, and 3-months during the intervention. The primary outcome is change in depression symptoms burden (using the Hamilton Rating Scale for Depression) from pre- to post-intervention and over 12 months of follow-up. DISCUSSION: WELL Study findings will inform the development of widely generalizable and scalable technology-based interventions to support bereaved spouses in community-based settings. Clinical http://Trials.gov Identifier: NCT04016896.

µ Opioid Antagonist Naltrexone Partially Abolishes the Antidepressant Placebo Effect and Reduces Orbitofrontal Cortex Encoding of Reinforcement.

BACKGROUND: Like placebo analgesia, the antidepressant placebo effect appears to involve cortical and subcortical endogenous opioid signaling, yet the mechanism through which opioid release affects mood remains unclear. The orbitofrontal cortex (OFC)-which integrates various attributes of a stimulus to predict associated outcomes-has been implicated in placebo effects and is rich in µ opioid receptors. We hypothesized that naltrexone blockade of µ opioid receptors would blunt OFC-dependent antidepressant placebo effects. METHODS: Twenty psychotropic-free patients with major depressive disorder completed a randomized, double-blind, placebo-controlled crossover study of 1 oral dose of 50 mg of naltrexone or matching placebo immediately before completing 2 sessions of the antidepressant placebo functional magnetic resonance imaging task. This task manipulates placebo-associated expectancies and their reinforcement while assessing expected and actual mood improvement. RESULTS: Behaviorally, manipulations of antidepressant placebo expectancies and their reinforcement had positive, interactive effects on participants' expectancy and mood ratings. The high-expectancy condition recruited the dorsolateral and ventrolateral prefrontal cortex, as well as dorsal attention stream regions. Interestingly, increased dorsolateral and ventrolateral prefrontal cortex brain responses appeared to attenuate the antidepressant placebo effect. The administration of 1 oral dose of naltrexone, compared with placebo, partially abolished the interaction of the expectancy and reinforcement manipulation on mood and blocked reinforcement-induced responses in the right central OFC. CONCLUSIONS: Our results show preliminary evidence for the role of µ opioid central OFC modulation in antidepressant placebo effects by positively biasing the value of placebo based on reinforcement and enhancing subsequent hedonic experiences.