Sleep Health, Inflammation, and Emotion Study

NCT02270619 | Completed Early Phase 1

• 1 other identifier: K23AG049085
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 1

Brief Summary

Late-life depression is a major public health burden due to its high prevalence and associated morbidity, suicide risk, functional decline, and mortality. Unfortunately, current antidepressant therapies have limited effectiveness; hence, biologically plausible models for new treatments are being pursued. Systemic inflammation is hypothesized to play an important role on the onset and perpetuation of depression, especially in older women. Aging processes involve a heightened inflammatory state, and both inflammatory disorders and depression are more prevalent in women than men. However, increased systemic inflammation does not necessarily lead to depression in all women. Even when robust systemic inflammation is experimentally induced (e.g. endotoxin administration), largely variable increases in depressive symptoms are found. Defining the factors that account for this variability may identify individuals at risk of developing depression when exposed to heightened inflammatory states such as aging, obesity, and chronic disease, and informs future translational studies of depression prevention. In particular, the role of sleep disturbance in explaining this variability requires further attention because it is an independent risk factor for depression and heightens systemic inflammation by increasing the production of proinflammatory cytokines. The investigators have also discovered that women, but not men, who report sleep disturbance including short sleep duration experience significantly more depressive symptoms in response to an inflammatory challenge than women without sleep disturbance. Thus, it is hypothesized that sleep loss is a vulnerability factor for inflammation-induced depressive symptoms in women. However, to date, no experimental approach has been used to evaluate the role of sleep loss on inflammation-induced depressive symptoms. This proposal aims to examine this hypothesis by partial sleep deprivation (PSD) followed by endotoxin challenge in older women. It also aims to explore genomic and socio- emotional mechanisms underlying the association between sleep loss and depressive symptoms. In a randomized controlled factorial design, 80 healthy female volunteers aged 60 to 80 will be randomly assigned to one of 4 arms: 1) uninterrupted sleep followed by placebo; 2) uninterrupted sleep followed by endotoxin; 3) PSD followed by placebo; or 4) PSD followed by endotoxin. Subjects will be administered placebo or endotoxin in the morning after PSD or uninterrupted sleep. Depressive symptoms will be repeatedly assessed over 6 hours after placebo or endotoxin administration.

Conditions

Depression

Outcome Measures

Primary Outcomes (1)

• Change in depressive symptoms from baseline

  Short Form of the Profile of Mood States (POMS-SF)

  At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after drug administration

Secondary Outcomes (3)

• Change in fatigue from baseline

  At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after drug administration

• Change in pain from baseline

  At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after drug administration

• Anhedonia

  2 hours after drug administration

Other Outcomes (2)

• Change in proinflammatory cytokines from baseline

  At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after drug administration

• Change in gene expression from baseline

  At baseline and then at 30 minutes after drug administration

Study Arms (4)

Uninterrupted sleep & placebo

PLACEBO COMPARATOR

Uninterrupted sleep followed by placebo

Other: Placebo; Other: Uninterrupted sleep

Uninterrupted sleep & endotoxin

EXPERIMENTAL

Uninterrupted sleep followed by endotoxin 0.8 ng/kg of body weight IV bolus

Biological: Endotoxin; Other: Uninterrupted sleep

Partial sleep deprivation & placebo

EXPERIMENTAL

Partial sleep deprivation followed by placebo

Behavioral: Partial sleep deprivation; Other: Placebo

Partial sleep deprivation & endotoxin

EXPERIMENTAL

Partial sleep deprivation followed by endotoxin 0.8 ng/kg of body weight IV bolus

Biological: Endotoxin; Behavioral: Partial sleep deprivation

Interventions

Endotoxin BIOLOGICAL

Low dose endotoxin (0.8 ng/kg of body weight) as IV bolus

Partial sleep deprivation & endotoxin; Uninterrupted sleep & endotoxin

Partial sleep deprivation BEHAVIORAL

Partial night sleep deprivation by staying awake from 23:00 to 03:00

Partial sleep deprivation & endotoxin; Partial sleep deprivation & placebo

Placebo OTHER

0.9% saline as IV bolus

Partial sleep deprivation & placebo; Uninterrupted sleep & placebo

Uninterrupted sleep OTHER

Uninterrupted sleep from 23:00 to 07:00

Uninterrupted sleep & endotoxin; Uninterrupted sleep & placebo

Eligibility Criteria

• Age: 60 Years - 80 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• to be in good general health
• to be female
• to be aged 60 to 80 years

You may not qualify if:

• presence of chronic mental or physical illnesses
• history of allergies, auto-immune, liver, or other chronic diseases
• current use of prescription medications such as steroids, non-steroid anti-inflammatory drugs, immune modifying drugs, opioid analgesics, and psychotropic medications
• current sleep disorders such as insomnia or sleep apnea
• nightshift work or time zone shifts (\> 3 hours) within the previous 6 weeks
• prior or current suicidal ideation assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)
• current depressive symptoms assessed by the Patient Health Questionnaire (PHQ-9) (≥ 5)
• sleep disorders identified by the SCID and the Duke Structured Interview for Sleep Disorders (DSISD)
• sleep disturbance defined by the Pittsburgh Sleep Quality Index (PSQI) (≥ 5)
• a positive screen for sleep apnea using the Berlin Sleep Apnea Questionnaire
• excessive caffeine use (\>600 mg/day)
• BMI \> 35 due to the effects of obesity on cytokine activity and risk for sleep disordered breathing
• evidence of recreational drug use from urine test
• any abnormalities on screening laboratory tests.

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

UCLA Cousins Center for Psychoneuroimmunology

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Depression

Interventions

Endotoxins

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Bacterial Toxins; Toxins, Biological; Biological Factors

Study Officials

• Hyong Jin Cho, MD, PhD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

• Michael R Irwin, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 15, 2014
• First Posted: October 21, 2014
• Study Start: October 1, 2014
• Primary Completion: January 1, 2021
• Study Completion: January 1, 2021
• Last Updated: February 18, 2021

Record last verified: 2021-02

Locations

US (1)