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

• ClinicalTrials.gov Identifier: NCT03256760
• Recruitment Status: Recruiting
• First Posted: August 22, 2017
• Last Update Posted: April 2, 2020
• Sponsor: Michael Irwin, MD
• Information provided by (Responsible Party): Michael Irwin, MD, University of California, Los Angeles

Study Description

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

Condition or disease	Intervention/treatment	Phase
Depression in Old Age	Biological: Endotoxin; Biological: Placebo	Phase 1

Detailed Description:

This study 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=80) vs. comparisons without insomnia (n=80), 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 160 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Endotoxin vs. Placebo
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Masking Description: Blinded infusion
• Primary Purpose: Other
• Official Title: Experimental Model of Depression in Aging: Insomnia, Inflammation, and Affect Mechanisms
• Actual Study Start Date: January 1, 2018
• Estimated Primary Completion Date: May 30, 2022
• Estimated Study Completion Date: May 30, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Endotoxin; Endotoxin 0.8 ng/kg body weight	Biological: Endotoxin; Endotoxin
Placebo Comparator: Placebo; Placebo	Biological: Placebo; Placebo

Outcome Measures

Primary Outcome Measures :

1. Depressed Mood Subscale of the Profile of Mood States (POMS) [ Time Frame: 12 hours ]
   The Depressed Mood Subscale of the POMS is a self-reported assessment of depressed mood in which subjects rate severity of depressed mood 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
2. Depressed mood and depressive symptoms as measured by the Montgomery Asberg Depression Rating Scale (MADRS) [ Time Frame: 12 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

Secondary Outcome Measures :

1. Emotion Facial Recognition Task [ Time Frame: about 2 hours ]
   This is a computer-based test that includes color photographs of facial expression of evoked-or felt-emotions: happy, sad, angry, fearful, disgusted, and nonemotional or neutral. Participants rate the emotional valence using a scale of 0-8 of each expression.
2. Emotion Intensity Task [ Time Frame: about 2 hours ]
   This is a computer-based test used along with emotion facial recognition to test subjective ratings of perceived intensity in response to facially-expressed emotions
3. Reward Learning Task [ Time Frame: about 2 hours ]
   This is a probabilistic reward task that is administered using computerized reward-learning task rooted in signal detection theory that yields an objective measurement of participant's ability to modulate behavior as a function of rewards. The variable that will be scored is termed response bias (RB), which reflects participants' preference for the stimulus paired with more frequent rewards.
4. Effort Expenditure for Reward Task [ Time Frame: about 2 hours ]
   Similar to the Reward Learning Task, this is a computer based reward task to evaluate reward processing in the context of monetary reward.
5. Social Reward Task [ Time Frame: about 2 hours ]
   This will evaluate another component of reward by subjective reports and task sensitivity to general social rewards

Other Outcome Measures:

1. Systemic marker of inflammation as indexed by interleukin-6 [ Time Frame: 12 hours ]
   Systemic inflammation as measured by circulating levels of interleukin-6 in plasma in pg/ml. Each timepoint is assayed and analyses examine the temporal profile of change with assessment every hour
2. Genomic marker of inflammation [ Time Frame: about 2 hours ]
   Transcriptional profile of inflammation as measured by Conserved Translational Response to Adversity in circulating peripheral blood mononuclear cells

Eligibility Criteria

• Ages Eligible for Study: 60 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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 assessed by the Structured Clinical Interview for Diagnosis, Diagnostic Statistical Manual 5 and the Duke Structured Interview for Sleep Disorders, and will be required to fulfill a minimal severity of mild insomnia with a Insomnia Severity Index score greater than 10, as well as evidence of poor sleep efficiency (<85%).
  • 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 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

Contacts and Locations

Contacts

Contact: Michael Irwin, MD; 3108258281; mirwin1@ucla.edu

Contact: Hyong Cho; 3108258281; hyongcho@mednet.ucla.edu

Locations

United States, California

Cousins Center for Psychoneuroimmunology, UCLA Neuropsychiatric Institute; Recruiting

Los Angeles, California, United States, 90095

Contact: Michael Irwin, MD 310-825-8281 mirwin1@ucla.edu

Contact: Hyong Cho, MD, PhD 310-260-7492 hyongjcho@mednet.edu

Principal Investigator: Michael R. Irwin, MD

Sponsors and Collaborators

Michael Irwin, MD

More Information

• Responsible Party: Michael Irwin, MD, Principal Investigator, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT03256760
• Other Study ID Numbers: 16-000583
• First Posted: August 22, 2017
• Last Update Posted: April 2, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Michael Irwin, MD, University of California, Los Angeles:

Insomnia, depression

Additional relevant MeSH terms:

Depression; Depressive Disorder; Behavioral Symptoms; Mood Disorders; Mental Disorders