Experimental Model of Depression in Aging: Insomnia, Inflammation, and Affect Mechanisms
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- Depressed Mood Subscale of the Profile of Mood States (POMS)
研究概览
简要总结
Late-life depression is a significant public health concern, and effective interventions for prevention and treatment are needed. Insomnia and inflammation are modifiable targets for depression prevention, and this study is significant in using an experimental approach (i.e., inflammatory challenge) to probe acute inflammatory- and depression responses as a function of insomnia, which will inform identification of molecular targets for pharmacologic interventions, and improvement of insomnia treatments to prevent depression in older adults.
Project
详细描述
This study (SHARE-D) will use an inflammatory challenge (i.e., endotoxin) to probe acute inflammatory- and depression responses (primary outcome) in older adults as a function of insomnia. Older adults with insomnia show chronic inflammation; sleep disturbance also activates inflammatory signaling; chronic inflammation primes acute inflammatory responses; chronic inflammation, as well as acute inflammatory reactivity, predict depression over the following year; and finally, endotoxin induces acute inflammation along with depressive symptoms, with preliminary evidence that "two-hits" (i.e., sleep disturbance and inflammatory challenge) are associated with exaggerated increases in depression, especially in women. In this placebo-controlled, randomized, double-blind study of low dose endotoxin in older adults (60-80 y; stratified by sex) with insomnia (n=60) vs. comparisons without insomnia (n=100), the investigators hypothesize that older adults with insomnia will show heightened inflammatory- and affective responding to inflammatory challenge as compared to those without insomnia. The investigation aims to: 1) examine differences in depressive symptoms and measures of negative affect responding as a function of insomnia and inflammatory challenge; 2) examine differences in measures of positive affect responding as a function of insomnia and inflammatory challenge; and 3) examine differences in experimentally-induced inflammation in relation to depressive symptoms and measures of negative- and positive affect responding as a function of insomnia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
Blinded infusion
入排标准
- 年龄范围
- 60 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants will be required to be in good general health (as evaluated during the phone and in-person baseline session)
- •Participants will be aged 60 to 80 years.
- •Half the participants (N=80) will be those with insomnia disorder as diagnosed by the Structured Clinical Interview for Diagnosis, Diagnostic Statistical Manual 5 and the Duke Structured Interview for Sleep Disorders, .
- •The other half will be those without insomnia identified as not having insomnia by any of these assessments.
排除标准
- •Following a structured telephone interview, prospective participants with the following conditions will not advance to the in-person baseline session:
- •Presence of chronic mental or physical illness (except for insomnia)
- •History of allergies, autoimmune, liver, or other severe chronic diseases,
- •Current and regular use of prescription medications such as steroids, non-steroid anti-inflammatory drugs, aspirin, immune modifying drugs, opioid analgesics, statins, antihypertensive drugs, anti-arrhythmic drugs, and antidepressant medications (none in the last 6 months); and nightshift work or time zone shifts (> 3hrs) within the previous 6 weeks, or previous history of fainting during blood draws.
- •Presence of co-morbid medical conditions not limited to but including cardiovascular (e.g., history of acute coronary event, stroke) and neurological diseases (e.g., Parkinson's disease), as well as pain disorders;
- •Presence of comorbid inflammatory disorders such as rheumatoid arthritis or other autoimmune disorders;
- •Presence of an uncontrolled medical condition that is deemed by the investigators to interfere with the proposed study procedures, or to put the study participant at undue risk;
- •Presence of chronic infection, which may elevate proinflammatory cytokines;
- •Presence of an acute infectious illness in the two weeks prior to an experimental session.
- •Current Axis I psychiatric disorders as determined by the Research Version of the Structured Clinical Interview including a current major depressive disorder and substance dependence (a prior history of depression is not an exclusion criterion, which will be considered for a pre-planned sensitivity analysis and will be used as a pre-classification variable in the generation of the two groups, and in the randomization schedule);
- •Lifetime history of suicide attempt or inpatient psychiatric admission. Sleep Disorders:
- •Current history of sleep apnea or nocturnal myoclonus;
- •Phase-shift disorder, which will be identified by the Structured Clinical Interview and the Duke Structured Interview for Sleep Disorders ; Medication and Substance Use:
- •Current and/or past regular use of hormone-containing medications including steroids;
- •Current and/or past regular use of non-steroid anti-inflammatory drugs;
- •Current and/or past regular use of immune modifying drugs that target specific immune responses such as cytokine antagonists;
- •Current and/or past regular use of analgesics such as opioids;
- •Current and/or past regular use of cardiovascular medications, including antihypertensive, antiarrhythmic, antianginal, and anticoagulant drugs;
- •Use of antidepressant medications or other psychotropic medications; (16) current smoking or excessive caffeine use (>600 mg/day) because of the known effects on proinflammatory cytokine levels;
- •Evidence of recreational drug use from urine test. Health Factors:
- •Body mass index > 35 because of the effects of obesity on proinflammatory cytokine activity and also on risk for sleep disordered breathing;
- •Any clinically significant abnormality on screening laboratory tests
- •Clinically significant abnormalities in electrocardiogram
研究组 & 干预措施
Endotoxin
Endotoxin 0.8 ng/kg body weight
干预措施: Endotoxin (Biological)
Placebo
Placebo
干预措施: Placebo (Biological)
结局指标
主要结局
Depressed Mood Subscale of the Profile of Mood States (POMS)
时间窗: 12 hours
The Depressed Mood Subscale of the POMS is a self-and observer rated assessment of depressed mood in which severity of depressed mood is rated using a visual analog scale from 1 to 5 (5 being most severe). Each timepoint is scored and analyses examine the temporal profile of change with assessment every hour
Depressed mood and depressive symptoms as measured by the Montgomery Asberg Depression Rating Scale (MADRS)
时间窗: 8 hours
Depressed mood and depressive symptom severity by self-reported assessment using the Montgomery Asberg Depression Rating scale with a range from 0 to 54 with a higher score indicating more severe depressive symptoms. Each timepoint is scored and analyses examine the temporal profile of change with assessment every 2 hours
次要结局
- Emotion Intensity Task(about 2 hours)
- Effort Expenditure for Reward Task(about 2 hours)
- Temporal Experience of Pleasure Scale(8 hours)
- Hamilton Depression Rating Scale(8 hours)
- Emotion Facial Recognition Task(about 2 hours)
- Social Reward Task(about 2 hours)
- Probabilistic Reward Task(about 2 hours)
- Snaith-Hamilton Pleasure Scale(8 hours)
研究者
Michael Irwin, MD
Principal Investigator
University of California, Los Angeles