Sleep Health, Inflammation, and Emotion Study

Depression Clinical Trial

— SHINE  

Official title:

Sleep Loss as a Vulnerability Factor for Inflammation Induced Depressive Symptoms in Older Women

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02270619
• Other study ID #: K23AG049085
• Status: Completed
• Phase: Early Phase 1
• Start date: October 2014
• Est. completion date: January 2021

Study information

• Verified date: February 2021
• Source: University of California, Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 95
• Est. completion date: January 2021
• Est. primary completion date: January 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 60 Years to 80 Years

Eligibility

Inclusion Criteria:

• to be in good general health

• to be female

• to be aged 60 to 80 years

Exclusion Criteria:

• 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

• an Axis I psychiatric disorder as determined by the Research Version of the Structured Clinical Interview for DSM-5 (SCID-5-RV) including a current or within 1 year prior-to-study history of major depressive disorder (a history of depression 1 or more years prior to the study is not an exclusion criterion, which will be considered for a pre-planned sensitivity analysis, however, any prior depressive episode severe enough to have involved suicidal ideation or required an inpatient psychiatric admission is an exclusion criterion)

• 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.

Related Conditions & MeSH terms

• Depression
• Inflammation

Intervention

Biological:
• Endotoxin
Low dose endotoxin (0.8 ng/kg of body weight) as IV bolus

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

Other:
• Placebo
0.9% saline as IV bolus
• Uninterrupted sleep
Uninterrupted sleep from 23:00 to 07:00

Locations

Country	Name	City	State
United States	UCLA Cousins Center for Psychoneuroimmunology	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Los Angeles

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in proinflammatory cytokines from baseline	Circulating proinflammatory cytokines ((interleukin-1 receptor antagonist, interleukin-6, tumor necrosis factor-a, and soluble tumor necrosis factor receptor)	At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after drug administration
Other	Change in gene expression from baseline	Genome-wide transcriptional profiling; Expression of genes involved in proinflammatory pathways and in circadian clock network	At baseline and then at 30 minutes after drug administration
Primary	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	Change in fatigue 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	Change in pain from baseline	Modified Pennebaker Inventory of Limbic Languidness (PILL) and Visual Analogue Scale (VAS)	At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after drug administration
Secondary	Anhedonia	Facial expressions and skin conductance in response to funny film clips	2 hours after drug administration