Experimental Model of Depression in Aging: Insomnia, Inflammation, and Affect Mechanisms (SHARE-D)

  • End date
    May 30, 2023
  • participants needed
  • sponsor
    Michael Irwin, MD
Updated on 24 October 2022
Accepts healthy volunteers


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.



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.

Condition Depression in Old Age
Treatment Placebo, Endotoxin
Clinical Study IdentifierNCT03256760
SponsorMichael Irwin, MD
Last Modified on24 October 2022


Yes No Not Sure

Inclusion Criteria

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

Exclusion Criteria

Following a structured telephone interview, prospective participants with the following conditions will not advance to the in-person baseline
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
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
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