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Probiotic (LGG) for Veterans With PTSD

Phase 2
Completed
Conditions
Post Traumatic Stress Disorder
Inflammation
Interventions
Biological: Lactobacillus rhamnosus GG (LGG; ATCC strain 53103; CRMTS #11272; PTS #3766)
Other: Placebo
Registration Number
NCT04150380
Lead Sponsor
VA Eastern Colorado Health Care System
Brief Summary

Exaggerated inflammation in the body and brain is thought to play a role in the vulnerability to and aggravation and perpetuation of adverse consequences among those with posttraumatic stress disorder (PTSD). The proposed study begins the process of investigating the use of a natural immunoregulatory/anti-inflammatory probiotic, Lactobacillus rhamnosus GG (LGG; ATCC53103), to treat chronic symptoms associated with PTSD among Veterans. By looking at the impact of probiotic supplementation on biological signatures of increased inflammation, as reflected by biomarkers of inflammation, gut microbiota composition, intestinal permeability, stress response, decision making, and PTSD symptoms, this study may identify a novel intervention for the treatment of symptoms associated with this frequently occurring condition.

Detailed Description

United States military Veterans from recent conflicts are coping with symptoms related to posttraumatic stress disorder (PTSD). Many Veterans are resistant to conventional health and mental health interventions (e.g., medication, psychotherapy), and often symptoms are not significantly improved by traditional treatments. Alternative treatment methods are needed. An underlying feature of PTSD is exaggerated inflammation, both peripherally and in the central nervous system, which is thought to play an important role in the vulnerability to, aggravation of, and perpetuation of adverse consequences of this condition. Therefore, an innovative intervention strategy would be the use of immunoregulatory/anti-inflammatory probiotics to reduce inflammation. In this study, the investigators will investigate the effects of an 8-week oral administration of an immunoregulatory probiotic, Lactobacillus rhamnosus GG (LGG; ATCC53103), a probiotic shown to have anti-inflammatory and immunoregulatory effects (i.e., decreases in C-reactive protein \[CRP\]). Project aims will be assessed using a longitudinal, double blind, randomized placebo-controlled design. After initial evaluation procedures to confirm PTSD diagnosis, 59 participants will be randomized to probiotic supplementation and 59 will be randomized to placebo supplementation.

Primary Aim. Demonstrate the effects of LGG in a cohort of OEF/OIF Veterans with PTSD and Functional Bowel Disorders (FBD), including IBS, on plasma CRP concentrations (mechanistic, primary outcome), and PTSD symptom severity (clinical, exploratory). Additional biological signatures associated with this condition will be considered exploratory, including gut microbial community and intestinal permeability \[IP\]), other biological signatures of inflammation, as well as stress responsivity and decision making. Hypothesis 1.1. Those who receive LGG supplementation will respond with lower plasma levels of CRP as compared to those allocated to placebo. Exploratory Hypothesis 1.2. Those who receive LGG supplementation will respond with decreased PTSD symptoms (PCL-5), as compared to those allocated to placebo. Exploratory Hypothesis 1.3. Those who receive LGG supplementation will respond with increased abundance of LGG and community-level shifts (e.g.,increased alpha diversity) in the gut microbiota (measured using qRT-PCR and DNA sequencing of the 16S rRNA gene, respectively), decreases in IP (decreased fatty acid binding protein 215 and D-amino acid oxidase16), increases in plasma concentrations of anti-inflammatory biomarkers (IL-10, IL-4), decreases in additional plasma biomarkers of inflammation (IL-6, IL-8, IFNγ, IL- 1α, IL-1β, and IL-12p70), reduced stress response (biological and psychological) during and after Cyberball, and improved decision-making (measured by performance on the modified Iowa Gambling Test \[mIGT\]) as compared to those allocated to placebo. Exploratory Hypothesis 1.4. The effect of LGG supplementation on stress response, decision-making, and PTSD symptom severity is mediated by effects of LGG supplementation on the gut microbiota, intestinal permeability, and plasma biomarkers of inflammation.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
383
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
SupplementLactobacillus rhamnosus GG (LGG; ATCC strain 53103; CRMTS #11272; PTS #3766)8 weeks of dietary augmentation with oral LGG 1.0 x 1010 colony forming units (CFU) once daily (delivered in a size 1 capsule)
PlaceboPlacebo8 weeks of dietary augmentation with placebo once daily (delivered in a size 1 capsule)
Primary Outcome Measures
NameTimeMethod
Plasma concentration of C-reactive protein (CRP)Change from basline to directly following the 8 week intervention

Blood biomarker of inflammation

Secondary Outcome Measures
NameTimeMethod
PTSD symptoms per the PTSD Checklist for DSM-5 (PCL-5)Change from basline to directly following the 8 week intervention

PTSD symptoms

Plasma concentration of inflammatory markersChange from basline to directly following the 8 week intervention

IL-10, IL-4, IL-6, IL-8, IFNy, IL-1a, IL-1b, and IL-12p70

Type and abundance measurement of gut microbiotaChange from basline to directly following the 8 week intervention

qRT-PCR and DNA sequencing of the 16S rRNA gene

Decision-makingImmediately post-intervention

Iowa Gambling Test

Plasma concentration of intestinal permeabilityChange from basline to directly following the 8 week intervention

fatty acid binding protein 2 and D-amino acid oxidase

Biological and psychological stress responseImmediately post-intervention

Cyberball

Trial Locations

Locations (1)

VA Rocky Mountain Regional Center

🇺🇸

Denver, Colorado, United States

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