Sleep and Healthy Aging Research for Depression (SHARE-D) Study

NCT ID: NCT03256760

Last Updated: 2024-09-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-23
• Study Completion Date: 2024-04-30

Brief Summary

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

Detailed Description

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.

Conditions

Depression in Old Age

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

Endotoxin

Endotoxin 0.8 ng/kg body weight

Group Type: EXPERIMENTAL

Endotoxin

Intervention Type: BIOLOGICAL

Endotoxin

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Placebo

Interventions

Endotoxin

Endotoxin

Intervention Type: BIOLOGICAL

Placebo

Placebo

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• 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

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Michael Irwin, MD

OTHER

Sponsor Role: lead

Responsible Party

Michael Irwin, MD

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Cousins Center for Psychoneuroimmunology, UCLA Neuropsychiatric Institute

Los Angeles, California, United States

Countries

United States

References

Irwin MR, Boyle CC, Cho JH, Piber D, Sadeghi N, Castillo D, Smith MT, Eisenberger NI, Olmstead R. Inflammatory Exposure and Depression in Older Adults With Insomnia: A Randomized Clinical Trial. JAMA Psychiatry. 2025 Sep 1;82(9):859-867. doi: 10.1001/jamapsychiatry.2025.1327.

Reference Type: DERIVED

PMID: 40668551 (View on PubMed)

DuPont CM, Olmstead R, Reid MJ, Hamilton KR, Campbell CM, Finan PH, Sadeghi N, Castillo D, Irwin MR, Smith MT. A randomized, placebo-controlled, double-blinded mechanistic clinical trial using endotoxin to evaluate the relationship between insomnia, inflammation, and affective disturbance on pain in older adults: A protocol for the sleep and Healthy Aging Research for pain (SHARE-P) study. Brain Behav Immun Health. 2023 May 19;30:100642. doi: 10.1016/j.bbih.2023.100642. eCollection 2023 Jul.

Reference Type: DERIVED

PMID: 37256193 (View on PubMed)

Other Identifiers

16-000583

Identifier Type: -

Identifier Source: org_study_id