Clinical trial NCT03256760: Sleep and Healthy Aging Research for Depression (SHARE-D) Study
Official title: Experimental Model of Depression in Aging: Insomnia, Inflammation, and Affect Mechanisms
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Depression in Old Age
Keywords: Insomnia, depression
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
First posted: 2017-08-22
Enrollment: 160
Sex: ALL
Minimum age (years): 60
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Endotoxin vs. Placebo
Primary purpose: OTHER

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.

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: 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

Primary outcomes:
measure: Depressed Mood Subscale of the Profile of Mood States (POMS)
timeFrame: 12 hours
measure: Depressed mood and depressive symptoms as measured by the Montgomery Asberg Depression Rating Scale (MADRS)
timeFrame: 8 hours
Secondary outcomes:
measure: Hamilton Depression Rating Scale
timeFrame: 8 hours
measure: Emotion Facial Recognition Task
timeFrame: about 2 hours
measure: Emotion Intensity Task
timeFrame: about 2 hours
measure: Probabilistic Reward Task
timeFrame: about 2 hours
measure: Effort Expenditure for Reward Task
timeFrame: about 2 hours
measure: Social Reward Task
timeFrame: about 2 hours
measure: Snaith-Hamilton Pleasure Scale
timeFrame: 8 hours
measure: Temporal Experience of Pleasure Scale
timeFrame: 8 hours
Other outcomes:
measure: Feelings of Social Disconnection
timeFrame: 12 hours
measure: Physical symptoms
timeFrame: 12 hours
measure: Psychiatric symptoms
timeFrame: 6 hours
measure: Systemic marker of inflammation as indexed by interleukin-6
timeFrame: 12 hours
measure: Genomic marker of inflammation
timeFrame: about 2 hours
measure: UCLA Loneliness Scale
timeFrame: 6 hours
measure: Social Status
timeFrame: 6 hours
measure: Perceived Social Support
timeFrame: 6 hours
measure: Social Attachment
timeFrame: 6 hours
measure: Sensitivity to Social Rejection
timeFrame: 6 hours
measure: Cyberball Social Exclusion Task
timeFrame: 2 hours
measure: Cognitive Processing
timeFrame: 5.5 hours
measure: Mechanical Temporal Summation
timeFrame: 5.5. hours
measure: Conditioned Pain Modulation
timeFrame: 5.5 hours
measure: Affective Pain Modulation
timeFrame: 5.5
measure: Pressure Pain Threshold-Trapezius muscle
timeFrame: 5.5 hours
measure: Heat Pain Threshold
timeFrame: 5.5 hours
measure: Heat Pain Tolerance
timeFrame: 5.5 hours
measure: Cold Pain Tolerance
timeFrame: 5.5
measure: Pain Pain Threshold. Masseter muscle and middle of quadriceps
timeFrame: 5.5 hours
measure: Pain Intensity
timeFrame: 12 months
measure: Depressive symptoms
timeFrame: 12 months
measure: Graded Chronic Pain Scale
timeFrame: 12 months
measure: Affective Disturbance
timeFrame: 12 months
measure: Sleep Continuity
timeFrame: 12 months
measure: Total Sleep Time
timeFrame: 12 months
Locations:
city: Los Angeles
country: United States
facility: Cousins Center for Psychoneuroimmunology, UCLA Neuropsychiatric Institute
state: California
Study officials:
References: