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Sleep and Healthy Aging Research on Depression for Younger Women

Primary Purpose

Anhedonia, Depression

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Endotoxin
Placebo
Sponsored by
University of California, Los Angeles
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Anhedonia

Eligibility Criteria

25 Years - 44 Years (Adult)FemaleAccepts Healthy Volunteers

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 biologically female and premenopausal (as evaluated by self report).
  • Participants will 25-44 years of age.

Exclusion Criteria:

  • Presence of chronic mental or physical illness
  • 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).
  • Nightshift work or time zone shifts (> 3hrs) within the previous 6 weeks
  • 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
  • Lifetime history of suicide attempt or inpatient psychiatric admission.
  • 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
  • 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.
  • Body mass index > 35 because of the effects of obesity on proinflammatory cytokine activity
  • Any clinically significant abnormality on screening laboratory tests
  • Clinically significant abnormalities in electrocardiogram

Sites / Locations

  • Norman Cousins Center for Psychoneuroimmunology, University of California, Los Angeles

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Endotoxin

Placebo

Arm Description

Endotoxin 0.8 ng/kg body weight; 1 infusion

same volume of 0.9% saline

Outcomes

Primary Outcome Measures

Non-social (monetary) reward response (reward motivation, learning, sensitivity)
Motivation for monetary reward is assessed with a 10-minute version of the Effort Expenditure for Rewards Task (EEfRT); change in the amount of hard trials chosen from baseline to post-injection is the outcome measure. Implicit reward learning and sensitivity to monetary reward is assessed with the probabilistic reward task (PRT); change in the magnitude of response bias from baseline to post-injection is the outcome measure.
General social reward response (reward sensitivity and motivation)
Sensitivity to general social reward cues (i.e., response to positive emotional faces) assessed as positive attentional bias with an emotional dot probe task and positive emotion detection with a face morphing task. Outcomes are change from baseline to post-injection in attentional bias (via reaction time) and identification (via reaction time and accuracy) of positive faces. Motivation for general social reward is assessed via self-report; participants rate their desire to engage in 3 different activities, one of which is social, on a 1 (not at all) to 10 (extremely) Likert scale.; change in desire for the social activity from baseline to post-injection is the outcome variable.

Secondary Outcome Measures

Close social reward response
Participants spend 5 minutes talking about a "close other" to a research assistant trained in reflective listening and provide ratings of current negative and positive emotion on visual analogue scales (0=not at all; 100=extremely) using items from the Profile of Mood States. Outcome variables are change in self-report positive emotion from pre to post-discussion, and percentage of positive and negative emotional words used during the discussion (scored with Linguistic Inquiry and Word Count Software).
Anticipatory and Consummatory Daily Reward Response
Participants indicate the extent to which they enjoyed 10 activities (social, non-social, close social) on a 0-100 visual analogue scale (0= not at all; 100=extremely) at five random times during the day; change in enjoyment in each of the domains from pre to post-experimental session is the outcome for consummatory reward. From the same list of activities, participants then rate how much they are currently looking forward to each activity on the same analogue scale (0= not at all; 100=extremely); change from pre to post-experimental session is the outcome for anticipatory reward.
Dopaminergic activity
Count of eye blinks (resting eye blink rate; EBR) over a five minute period; the outcome is change in EBR from pre to post-injection.
Depressed Mood Subscale of the Profile of Mood States (POMS)
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

Full Information

First Posted
February 19, 2019
Last Updated
May 8, 2023
Sponsor
University of California, Los Angeles
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1. Study Identification

Unique Protocol Identification Number
NCT03848715
Brief Title
Sleep and Healthy Aging Research on Depression for Younger Women
Official Title
Sleep and Healthy Aging Research on Depression for Younger Women
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 2, 2019 (Actual)
Primary Completion Date
July 22, 2022 (Actual)
Study Completion Date
May 2, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, Los Angeles

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Compelling evidence indicates inflammation plays a role in depression, but potential mechanisms linking inflammation to depression, such as dysregulated reward processing, are poorly understood. This study comprehensively evaluates effects of inflammation on reward across dimensions (e.g., anticipating versus receiving a reward) and types (e.g., money vs. smiling faces) in younger and older women. Characterizing how inflammation shapes the dynamic and multidimensional reward system, and how this may differ by age, may give insight into risk factors for depression and help identify critical points for intervention.
Detailed Description
This study will use an inflammatory challenge (i.e., endotoxin) to assess effects of inflammation on the behavioral response to social and non-social rewards, using tasks that assess reward motivation, sensitivity, and learning. Both elevated inflammation and reward dysregulation are associated with depression and have been shown to predict depression onset; understanding how inflammation alters the reward system in the laboratory setting may provide insight into risk factors and help identify potential areas for intervention. In this placebo-controlled, randomized, double-blind study of low dose endotoxin in 40 adult premenopausal women (25-44 y), the investigators will examine effects of endotoxin on reward responsiveness across dimensions (i.e., motivation, sensitivity, learning) and reward types (e.g., social and non-social). The investigators hypothesize that as compared to placebo, endotoxin will 1) decrease non-social reward responses across reward dimensions; 2) decrease "general" social reward responses across reward dimensions; 3) increase "close" social reward responses across reward dimensions; 4) decrease resting eye blink rate (EBR); EBR will be correlated with learning and motivation for non-social reward. The second component of the study is to examine whether effects of endotoxin on reward differ as a function of age; in particular it is hypothesized that effects will be more robust in younger compared to older women. In order to test for age differences, this study will use data from 40 older women (65+ y) participating in a parallel ongoing randomized controlled trial (ClinicalTrials.gov Identifier: NCT03256760). Thus, the investigation aims to: 1) Evaluate effects of inflammation on non-social reward as a function of age; 2) Evaluate effects of inflammation on general and close social reward as a function of age; 3) Examine changes in dopaminergic activity as a mechanism linking effects of inflammation on non-social reward processing as a function of age.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anhedonia, Depression

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Endotoxin vs Placebo
Masking
ParticipantCare ProviderOutcomes Assessor
Masking Description
Blinded infusion
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Endotoxin
Arm Type
Experimental
Arm Description
Endotoxin 0.8 ng/kg body weight; 1 infusion
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
same volume of 0.9% saline
Intervention Type
Biological
Intervention Name(s)
Endotoxin
Intervention Description
Endotoxin
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Non-social (monetary) reward response (reward motivation, learning, sensitivity)
Description
Motivation for monetary reward is assessed with a 10-minute version of the Effort Expenditure for Rewards Task (EEfRT); change in the amount of hard trials chosen from baseline to post-injection is the outcome measure. Implicit reward learning and sensitivity to monetary reward is assessed with the probabilistic reward task (PRT); change in the magnitude of response bias from baseline to post-injection is the outcome measure.
Time Frame
Baseline and post-injection (approximately 2 hrs)
Title
General social reward response (reward sensitivity and motivation)
Description
Sensitivity to general social reward cues (i.e., response to positive emotional faces) assessed as positive attentional bias with an emotional dot probe task and positive emotion detection with a face morphing task. Outcomes are change from baseline to post-injection in attentional bias (via reaction time) and identification (via reaction time and accuracy) of positive faces. Motivation for general social reward is assessed via self-report; participants rate their desire to engage in 3 different activities, one of which is social, on a 1 (not at all) to 10 (extremely) Likert scale.; change in desire for the social activity from baseline to post-injection is the outcome variable.
Time Frame
Baseline and post-injection (approximately 2 hrs)
Secondary Outcome Measure Information:
Title
Close social reward response
Description
Participants spend 5 minutes talking about a "close other" to a research assistant trained in reflective listening and provide ratings of current negative and positive emotion on visual analogue scales (0=not at all; 100=extremely) using items from the Profile of Mood States. Outcome variables are change in self-report positive emotion from pre to post-discussion, and percentage of positive and negative emotional words used during the discussion (scored with Linguistic Inquiry and Word Count Software).
Time Frame
Post-injection (approximately 2 hrs)
Title
Anticipatory and Consummatory Daily Reward Response
Description
Participants indicate the extent to which they enjoyed 10 activities (social, non-social, close social) on a 0-100 visual analogue scale (0= not at all; 100=extremely) at five random times during the day; change in enjoyment in each of the domains from pre to post-experimental session is the outcome for consummatory reward. From the same list of activities, participants then rate how much they are currently looking forward to each activity on the same analogue scale (0= not at all; 100=extremely); change from pre to post-experimental session is the outcome for anticipatory reward.
Time Frame
14 days (7 days pre-injection; 7 days post-injection).
Title
Dopaminergic activity
Description
Count of eye blinks (resting eye blink rate; EBR) over a five minute period; the outcome is change in EBR from pre to post-injection.
Time Frame
Baseline and post-injection (approximately 2 hrs)
Title
Depressed Mood Subscale of the Profile of Mood States (POMS)
Description
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
Time Frame
12 hours
Other Pre-specified Outcome Measures:
Title
Positive and negative emotion regulation capacity
Description
Participants complete a 30 minute standardized emotion regulation task that includes two phases: a reactivity phase and a regulation phase, and assesses the ability to up-regulate positive emotional response to standardized images, and down-regulate negative emotional response to standardized images, both using instructed reappraisal strategies. The dependent variable is the degree to which self-reported emotion changes when reacting to versus reappraising emotion stimuli. Participants rate how negative they feel (1=not at all; 5 = extremely) and how positive they feel (1=not at all; 5 = extremely).
Time Frame
post-injection (approximately 3 hrs)

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
44 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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 biologically female and premenopausal (as evaluated by self report). Participants will 25-44 years of age. Exclusion Criteria: Presence of chronic mental or physical illness 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). Nightshift work or time zone shifts (> 3hrs) within the previous 6 weeks 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 Lifetime history of suicide attempt or inpatient psychiatric admission. 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 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. Body mass index > 35 because of the effects of obesity on proinflammatory cytokine activity Any clinically significant abnormality on screening laboratory tests Clinically significant abnormalities in electrocardiogram
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chloe C Boyle, PhD
Organizational Affiliation
University of California, Los Angeles
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Michael R Irwin, MD
Organizational Affiliation
University of California, Los Angeles
Official's Role
Principal Investigator
Facility Information:
Facility Name
Norman Cousins Center for Psychoneuroimmunology, University of California, Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Sleep and Healthy Aging Research on Depression for Younger Women

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