Sleep and Healthy Aging Research on Depression for Younger Women

• ClinicalTrials.gov Identifier: NCT03848715
• Recruitment Status: Recruiting
• First Posted: February 21, 2019
• Last Update Posted: November 3, 2020
• Sponsor: University of California, Los Angeles
• Information provided by (Responsible Party): Chloe Boyle, PhD, University of California, Los Angeles

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.

Condition or disease	Intervention/treatment	Phase
Anhedonia; Depression	Biological: Endotoxin; Biological: Placebo	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 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: Sleep and Healthy Aging Research on Depression for Younger Women
• Actual Study Start Date: October 2, 2019
• Estimated Primary Completion Date: June 2, 2021
• Estimated Study Completion Date: October 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Endotoxin; Endotoxin 0.8 ng/kg body weight; 1 infusion	Biological: Endotoxin; Endotoxin
Placebo Comparator: Placebo; same volume of 0.9% saline	Biological: Placebo; Placebo

Outcome Measures

Primary Outcome Measures :

1. Non-social (monetary) reward response (reward motivation, learning, sensitivity) [ Time Frame: Baseline and post-injection (approximately 2 hrs) ]
   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.
2. General social reward response (reward sensitivity and motivation) [ Time Frame: Baseline and post-injection (approximately 2 hrs) ]
   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 :

1. Close social reward response [ Time Frame: Post-injection (approximately 2 hrs) ]
   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).
2. Anticipatory and Consummatory Daily Reward Response [ Time Frame: 14 days (7 days pre-injection; 7 days post-injection). ]
   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.
3. Dopaminergic activity [ Time Frame: Baseline and post-injection (approximately 2 hrs) ]
   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.
4. 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

Other Outcome Measures:

1. Positive and negative emotion regulation capacity [ Time Frame: post-injection (approximately 3 hrs) ]
   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).

Eligibility Criteria

• Ages Eligible for Study: 25 Years to 44 Years (Adult)
• Sexes Eligible for Study: Female
• 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 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

Contacts and Locations

Contacts

Contact: Chloe C Boyle, PhD; 310 825 8788; ccboyle@ucla.edu

Locations

United States, California

Norman Cousins Center for Psychoneuroimmunology, University of California, Los Angeles; Recruiting

Los Angeles, California, United States, 90095

Contact: Chloe Boyle, PhD 310-825-8788

Sponsors and Collaborators

University of California, Los Angeles

Investigators

• Principal Investigator: Chloe C Boyle, PhD; University of California, Los Angeles
• Principal Investigator: Michael R Irwin, MD; University of California, Los Angeles

  Study Documents (Full-Text)

Documents provided by Chloe Boyle, PhD, University of California, Los Angeles:

Study Protocol and Statistical Analysis Plan  [PDF] February 19, 2019

More Information

• Responsible Party: Chloe Boyle, PhD, Postdoctoral Fellow, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT03848715
• Other Study ID Numbers: 16-000583-AM-00016
• First Posted: February 21, 2019
• Last Update Posted: November 3, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Anhedonia; Depression; Depressive Disorder; Behavioral Symptoms; Mood Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases