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

NCT03256760 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 16-000583
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

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

Conditions

Depression in Old Age

Keywords

Insomnia, depression

Outcome Measures

Primary Outcomes (2)

• Depressed Mood Subscale of the Profile of Mood States (POMS)

  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

  12 hours

• Depressed mood and depressive symptoms as measured by the Montgomery Asberg Depression Rating Scale (MADRS)

  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

  8 hours

Secondary Outcomes (8)

• Hamilton Depression Rating Scale

  8 hours

• Emotion Facial Recognition Task

  about 2 hours

• Emotion Intensity Task

  about 2 hours

• Probabilistic Reward Task

  about 2 hours

• Effort Expenditure for Reward Task

  about 2 hours

Other Outcomes (26)

• Feelings of Social Disconnection

  12 hours

• Physical symptoms

  12 hours

• Psychiatric symptoms

  6 hours

Study Arms (2)

Endotoxin

EXPERIMENTAL

Endotoxin 0.8 ng/kg body weight

Biological: Endotoxin

Placebo

PLACEBO COMPARATOR

Placebo

Biological: Placebo

Interventions

Endotoxin BIOLOGICAL

Endotoxin

Endotoxin

Placebo BIOLOGICAL

Placebo

Placebo

Eligibility Criteria

• Age: 60 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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;

Sponsors & Collaborators

• Michael Irwin, MD: lead

Study Sites (1)

Cousins Center for Psychoneuroimmunology, UCLA Neuropsychiatric Institute

Los Angeles, California, 90095, United States

Location

Related Publications (3)

• Boyle CC, Cho JH, Eisenberger NI, Olmstead R, Sadeghi N, Castillo D, Irwin MR. Inflammation-induced depressed mood and reward responsivity as a function of age in female adults: a randomized controlled trial of endotoxin. Transl Psychiatry. 2025 Nov 26;16(1):6. doi: 10.1038/s41398-025-03752-2.

  PMID: 41298372 DERIVED

• 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.

  PMID: 40668551 DERIVED

• 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.

  PMID: 37256193 DERIVED

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders; Depression

Interventions

Endotoxins

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Bacterial Toxins; Toxins, Biological; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Blinded infusion
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Endotoxin vs. Placebo

Study Record Dates

• First Submitted: August 11, 2017
• First Posted: August 22, 2017
• Study Start: August 23, 2017
• Primary Completion: April 30, 2024
• Study Completion: April 30, 2024
• Last Updated: September 5, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: One year after study completion
• Access Criteria: Contact PI to obtain permission for data release

Locations

US (1)