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Trial record 1 of 8 for:    Michael R. Irwin AND depression
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Sleep and Healthy Aging Research for Depression (SHARE-D) Study (SHARE-D)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03256760
Recruitment Status : Recruiting
First Posted : August 22, 2017
Last Update Posted : October 4, 2022
Sponsor:
Information provided by (Responsible Party):
Michael Irwin, MD, University of California, Los Angeles

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 (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.

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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, 2023
Estimated Study Completion Date : May 30, 2023

Resource links provided by the National Library of Medicine


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

Placebo Comparator: Placebo
Placebo
Biological: Placebo
Placebo




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-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

  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. Hamilton Depression Rating Scale [ Time Frame: 8 hours ]
    The Hamilton Depression Rating Scale is on the most widely used scales in depression, which is adapted to evaluate acute changes in depressive symptoms. A trained interviewer, blind to the experimental condition, make ratings of items of depressed mood, feelings of guilt, loss of interest, retardation/agitation, anxiety, and somatic symptoms using items from the Hamilton Depression Rating Scale. The 17-item version will be used.

  2. 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.

  3. 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

  4. Probabilistic Reward 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.

  5. 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.

  6. 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

  7. Snaith-Hamilton Pleasure Scale [ Time Frame: 8 hours ]
    The Snaith-Hamilton Pleasure Scale (SHAPS) is a self-administered questionnaire with 14 items assessing four domains of pleasure response/hedonic experience: interest/pastimes, social interaction, sensory experience, and food/drink, with each item scored from 1 to 4.

  8. Temporal Experience of Pleasure Scale [ Time Frame: 8 hours ]
    This self-report scale rates interest in 10 different activities, how much a person is interested in doing that activity right now


Other Outcome Measures:
  1. Physical symptoms [ Time Frame: 12 hours ]
    Physical "sickness" symptoms which have been related to the administration of endotoxin are assessed during the experimental protocol; these sickness symptoms include self-reported rating of severity of muscle pain, shivering, nausea, breathing, difficulties, and fatigue

  2. 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

  3. 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

  4. Feelings of Social Disconnection [ Time Frame: 12 hours ]
    Using the Feelings of Social Disconnection Scale, participant rated the extent to which they were feeling the ''following feelings right now" on a 5-point Likert scale (1-not at all, to 5- very much so): (1) ''I feel like being around other people," (2) ''I feel like being alone," (3) ''I feel overly sensitive around others (e.g., my feelings are easily hurt)," (4) ''I feel connected to others," and (5) ''I feel disconnected from others." Items 1 and 4 were reverse-coded, and scores were averaged at each time point to create a measure of self-reported social disconnection. Each timepoint is scored and analyses examine the temporal profile of change with assessment every hour

  5. UCLA Loneliness Scale [ Time Frame: 6 hours ]
    UCLA Loneliness scale is a 10-item scale designed to measure one's subjective feelings of loneliness as well as feelings of social isolation. Participants rate each item as either O ("I often feel this way"), S ("I sometimes feel this way"), R ("I rarely feel this way"), N ("I never feel this way").

  6. Social Status [ Time Frame: 6 hours ]
    MacArthur Scale of Subjective Social Status (i.e., Social Ladder) will be used to evaluate perceived social status

  7. Perceived Social Support [ Time Frame: 6 hours ]
    Social Support Questionnaire Scale will be used to evaluated perceived social support

  8. Social Attachment [ Time Frame: 6 hours ]
    The Attachment Style Questions will be used to evaluate feelings of social attachment. This scale is reported 18 items that rates how you feel generally experience in relationships, not just in what is happening in a current relationship.

  9. Sensitivity to Social Rejection [ Time Frame: 6 hours ]
    Sensitivity to social rejection is examined by Fear of Negative Evaluation Scale and Mehrabian Rejection Sensitivity Scale

  10. Cyberball Social Exclusion Task [ Time Frame: 2 hours ]
    The Cyberball Social Exclusion Task is a virtual ball-toss game in which a participant plays with two other players (virtual) on a computer. Abruptly, the others exclude the participant, only throwing to one another. After completion of the task, the degree of perceived ostracism was was evaluated by a 20-item ostracism distress or social exclusion scale.

  11. Psychiatric symptoms [ Time Frame: 6 hours ]
    The Brief Symptom Inventory will be used assesses a wide variety of psychiatric symptoms

  12. Cognitive Processing [ Time Frame: 5.5 hours ]
    Increasing evidence indicates that inflammatory challenge acutely alters measures of cognitive performance, including spatial learning and memory. We use a virtual Morris Water Maze task (REF: https://pubmed.ncbi.nlm.nih.gov/19121374/) to assess computerized spatial learning and memory, followed by a Room Reconstruction Task (REF: https://pubmed.ncbi.nlm.nih.gov/10779831/) to assess the ability of cognitive mapping under real-life conditions.

  13. Mechanical Temporal Summation [ Time Frame: 5.5. hours ]
    Temporal summation reflects the endogenous capacity to enhance pain and is calculated by subtraction the highest mechanical pain rating from the first mechanical pain rating. Higher values are indicative of greater pain facilitation. This variable is a primary outcome for the pain testing substudy (SHARE-Pain or SHARE-P.

  14. Conditioned Pain Modulation [ Time Frame: 5.5 hours ]
    Conditioned pain modulation assesses the degree to which one noxious stimulus reduces pain produced by a second noxious stimulus and is a measure of endogenous capacity for pain inhibition. It is calculated by taking the average percent change (across four trials post injection; single trial at orientation visit) in pressure pain threshold during the cold pressor tasks compared to the pain pressure threshold assessed prior to cold water submersion. Larger values indicate better pain inhibitory capacity. This variable is a primary outcome for the SHARE-P.

  15. Affective Pain Modulation [ Time Frame: 5.5 ]
    Affective pain modulation refers to the ability of negative emotions to enhance pain sensitivity while positive emotions reduce pain sensitivity. Participants were asked to rate their pain on a 0 (no pain) to 100 (most extreme pain) scale and self-reported pain will be compared across the three conditions (negative, positive, neutral). Affective pain modulation is a primary outcome for SHARE-P.

  16. Pain Intensity [ Time Frame: 12 months ]
    o Pain intensity ratings will be assessed daily using a Visual Analogue Scale and averaged across the two week period to determine the Pain Intensity Index. These ratings will be made at baseline, 3mo, 6mo, 9mo, and 12mo and are considered a primary outcome for the longitudinal component of SHARE-P.

  17. Depressive symptoms [ Time Frame: 12 months ]
    Depressive symptoms will be assessed at baseline, 3mo, 6mo, 9mo, and 12mo using the Patient Health Questionnaire - 9 item (PHQ-9). This is a primary outcome for the longitudinal component of SHARE-P.

  18. Pressure Pain Threshold-Trapezius muscle [ Time Frame: 5.5 hours ]
    Pressure pain threshold is the first mechanical stimulus that a participant self-reports as painful, such that lower values indicate greater pain sensitivity. Pressure pain threshold was measured once during the orientation visit and will be averaged across two readings for the post-injection visit. Pressure pain threshold is a secondary outcome for SHARE-P.

  19. Heat Pain Threshold [ Time Frame: 5.5 hours ]
    The first thermal stimulus that participants self-report as painful (averaged across two trials). Lower values indicate enhanced pain sensitivity. This is a secondary outcome variable for the SHARE-P sub-study.

  20. Heat Pain Tolerance [ Time Frame: 5.5 hours ]
    The thermal stimulus at which the participant identifies the pain as intolerable (single trial at orientation visit; averaged across two trials post-injection). Lower values represent greater pain sensitivity. This is a secondary outcome variable for the SHARE-P sub-study.

  21. Graded Chronic Pain Scale [ Time Frame: 12 months ]

    Longitudinal assessments of pain using the Graded Chronic Pain Scale [Time Frame: 12 months]

    o Pain intensity and pain-related disability are assessed at baseline, 3mo, 6mo, 9mo, and 12mo using the Graded Chronic Pain Scale (3-month version). This is a secondary outcome for the SHARE-P study.


  22. Affective Disturbance [ Time Frame: 12 months ]
    o Affective disturbance is assessed daily during a 2-week period by having participants rate the extent to which they feel three positive (happy, calm, agreeable) and three negative emotions (sad, anxious, annoyed) on a 0 (not at all) to 100 (extremely) scale. Daily positive affect and negative affect are calculated by averaging across the three positive and negative emotion words, respectively. Participants complete these measures at baseline, 3mo, 6mo, 9mo and 12mo. This is a secondary outcome for SHARE-P.

  23. Sleep Continuity [ Time Frame: 12 months ]
    Electronic sleep diaries will be administered daily for two weeks at baseline, 3mo, 6mo, 9mo, and 12mo. Sleep diaries will be used to assess sleep continuity, including (1) latency to initial sleep onset, (2) frequency of nightly awakenings, (3) wake after sleep onset, (4) total sleep time, and (5) sleep efficiency (total sleep time/time in bed). These are considered secondary outcomes for SHARE-P.

  24. Total Sleep Time [ Time Frame: 12 months ]
    Participants will receive an ActiGraph (wrist triaxial accelerometer) to wear for a 2-week period at baseline, 3mo, 6mo, 9mo, and 12mo to measure total sleep time (secondary outcome for SHARE-P).

  25. Pain Pain Threshold. Masseter muscle and middle of quadriceps [ Time Frame: 5.5 hours ]
    • Pressure pain threshold is the first mechanical stimulus that a participant self-reports as painful, such that lower values indicate greater pain sensitivity. Pressure pain threshold is the average of two readings and will be reported separately for the masseter muscle and middle of the quadriceps. These are tertiary outcomes for SHARE-P.

  26. Cold Pain Tolerance [ Time Frame: 5.5 ]
    Cold pain tolerance is measured as the time it takes for the participant to withdraw their hand from cold water bath (2°C), such that shorter durations reflect greater pain sensitivity. (Tertiary outcome for SHARE-P).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   60 Years to 80 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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03256760


Contacts
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Contact: Michael Irwin, MD 3108258281 mirwin1@ucla.edu
Contact: Hyong Cho 3108258281 hyongcho@mednet.ucla.edu

Locations
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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
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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    Key Record Dates
Last Update Posted: October 4, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: One year after study completion
Access Criteria: Contact PI to obtain permission for data release

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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:
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Depression
Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders