Resistance Exercise to Treat Major Depression Via Cerebrovascular Mechanisms: Confirming Efficacy and Informing Precision Medicine
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 4
- 主要终点
- Change in depressive symptom severity measured by GRID Hamilton Depression Rating Scale (GRID-HAM-D)
研究概览
简要总结
Depression is a leading cause of disability worldwide and current treatments are ineffective for many people. This trial will investigate the efficacy of a 16-week high vs low dose resistance exercise training program for the treatment of Major Depressive Disorder (MDD) in 200 adults.
详细描述
Frontline treatments for major depressive disorder (MDD), including psycho- and pharmacotherapy, have limited effectiveness, and there is a critical need to develop and test novel, efficacious treatments for MDD and simultaneously work to optimize its benefits. Resistance exercise training (RET) is a promising but understudied treatment approach. This trial will investigate the efficacy of RET for treatment of MDD in a 1:1 randomized controlled trial (n=200) of 16 weeks of high vs low progressive RET in adults with DSM-5 diagnosed MDD. Further, this project will explore potential mechanisms leading to symptom improvement, including changes in cerebrovascular function (i.e., cerebral blood velocity and pulsatility) and self-efficacy, while also using supervised machine learning tools to predict depression changes, cerebrovascular changes, and participant adherence. Upon completion, this study will build towards identifying and translating mechanistically driven behavioral treatments to reduce the global burden of mental illness.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be diagnosed with DSM-5 MDD, confirmed via Structured Clinical Interview for DSM-5 (SCID).
- •Have current depressive symptoms of at least mild severity defined by the Hamilton Rating Scale of Depression 17 greater than or equal to 8 (HAMD; using the GRID-HAMD evaluated by trained, masked raters)
- •Be ages 18-65
- •EITHER not taking any mental health medications or seeking other mental health treatment (e.g., behavioral, psychological) OR be on a stable mental health medication and/or treatment regimen for the past 8 weeks, and intend to maintain that regimen for the duration of the study
- •Safe to exercise based on physical activity screening questions or physician clearance
- •Willing to be randomized to either condition
- •have a Smartphone
排除标准
- •Currently pregnant, nursing, or planning to become pregnant during the trial
- •Class III+ obesity
- •Diagnosed with lifetime or current Psychosis, Mania, or Bipolar Disorder, via the SCID
- •Diagnosed with current Substance Use Disorder, via the SCID
- •Active suicidal ideation with specific plan and intent ('5' score on Suicidal Ideation from Columbia Suicide Severity Rating Scale), which would necessitate immediate emergent care
- •Exhibit behavioral disturbance (e.g., aggression, mild-moderate cognitive impairment) that would significantly interfere with study participation, as assessed by clinical research personnel
- •Currently meets resistance exercise recommendations (2 days per week) for the last 8 weeks
- •Self-reporting a concussion/traumatic brain injury within the last 3 months
- •Having cardiovascular disease, uncontrolled hypertension, or uncontrolled diabetes
结局指标
主要结局
Change in depressive symptom severity measured by GRID Hamilton Depression Rating Scale (GRID-HAM-D)
时间窗: Weeks 0, 8, 16, 26, 52
The GRID-HAM-D is a clinician-completed questionnaire that will be used to rate depressive symptom severity. The questionnaire is designed for adults and is used to rate the intensity and frequency of depressive symptoms by probing mood, feelings of guilt, suicidal ideation, insomnia, agitation or retardation, anxiety, weight loss, and somatic symptoms. As recommended by the Depression Rating Scale Standardization Team, Clinical Interviewers will follow the Structured Interview Guide and use GRID scoring, in which dimensions of intensity and frequency of a symptom are rated independently for each item. Higher scores reflect greater symptom severity, categorized as Normal (0-7), Mild Depression (8-13), Moderate Depression (14-18), Severe Depression (19-22), and Very Severe Depression (\>23).
Cerebral blood velocity pulsatility
时间窗: Weeks 0, 8, 16, 26, 52
Cerebral blood pulsatility will be measured using the same techniques and conditions described for cerebral mean blood velocity, above for the MCA (primary outcome) and ACA (secondary outcome). Cerebral pulsatility will be quantified using the pulsatility index, calculated as (systolic - diastolic velocity)/mean velocity.
Change in self-reported depression symptom severity measured by Quick Inventory of Depressive Symptoms (QIDS)
时间窗: Weeks 0, 1-16 (once per week across the intervention), 26, 52
This is a self-administered 16-item questionnaire that assesses the severity of nine depressive symptoms in the last 7 days. Each item is rated on a 4-point scale (0-3), with total scores ranging from 0-27. Higher scores indicate more severe depression. This assessment is recommended because it is free, easily administered as a self-reported instrument for adults, and captures general symptoms of depression.
Cerebral mean blood velocity
时间窗: Weeks 0, 8, 16, 26, 52
Cerebral blood velocity will be measured under supine, resting conditions using non-invasive techniques following 10 min of quiet rest in a dimly lit room. Measurements will be taken from the middle (MCA, primary outcome) and anterior cerebral artery (ACA, secondary outcome) following standardized, recommended insonation protocols using 2 megahertz (MHz) transcranial Doppler (TCD) probes secured to the temporal window via a headset. MCA blood velocity waveforms will be collected over a 90-sec epoch and averaged. MCA mean blood velocity will be calculated using a standard algorithm implemented on the device.
次要结局
- Brachial blood pressure(Weeks 0, 8, 16, 26, 52)
- Change in exercise habits(Weeks 0, 1-16 (once per week across the intervention), 26, 52)
- Changes in general self efficacy measured by New General Self-Efficacy Scale(Weeks 0, 8, 16, 26, 52)
- Global cerebral blood flow(Weeks 0, 8, 16, 26, 52)
- Changes in RET-specific self efficacy measured by a modified version of the New General Self-Efficacy Scale(Weeks 0, 1-16 (once per week across the intervention), 26, 52)
- Carotid stiffness(Weeks 0, 8, 16, 26, 52)
- End-tidal Carbon Dioxide (CO2)(Weeks 0, 8, 16, 26, 52)
- Change in stress measured by Perceived Stress Scale (PSS-10)(Weeks 0, 8, 16, 26, 52)
- Average self-reported level of symptom improvement measured by Patient Global Impression of Change (PGIC)(Weeks 16, 26, and 52)
- Change in suicidal thoughts measured by Columbia-Suicide Severity Rating Scale (CSSRS)(Weeks 0, 8, 16, 26, 52)
- Change in muscular strength measured by Estimated 1 Repetition Maximum (RM) Strength Test(Weeks 0, 8, 16, 26, 52)
- Change in grip strength(Weeks 0, 8, 16, 26, 52)
- Change in worry measured by Penn State Worry Questionnaire (PSWQ)(Weeks 0, 8, 16, 26, 52)
- Change in monitor-assessed physical activity measured by accelerometry(Weeks 0, 8, 16, 26, 52 (worn 1 week following week 0 and 1 week after all other timepoints))
- Aortic stiffness(Weeks 0, 8, 16, 26, 52)
- Carotid blood pressure(Weeks 0, 8, 16, 26, 52)
- Blood Pressure Variability (BPV)(Weeks 0, 8, 16, 26, 52)
- Change in quality of life measured by 36-Item Short Form Health Survey (SF-36)(Weeks 0, 8, 16, 26, 52)
- Cerebrovascular reactivity to breath holds(Weeks 0, 8, 16, 26, 52)
- Heart Rate (HRV)(Weeks 0, 8, 16, 26, 52)
- Change in sleep measured by Insomnia Severity Index (ISI)(Weeks 0, 8, 16, 26, 52)
- Change in cognitive function measured by PROMIS-Cognitive Function SF (PROMIS)(Weeks 0, 8, 16, 26, 52)
- Change in emotional regulation measured by Emotional Regulation Questionnaire (ERQ)(Weeks 0, 8, 16, 26, 52)
- Change in exercise identity and intrinsic motivation(Weeks 0, 1-16 (once per week across the intervention), 26, 52)
- Change in self-reported physical activity measured by International Physical Activity Questionnaire (IPAQ)(Weeks 0, 8, 16, 26, 52)