- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04150380
Probiotic (LGG) for Veterans With PTSD
Biological Signature and Safety of an Immunomodulatory Probiotic Intervention for Veterans With PTSD
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Kelly A Stearns-Yoder
- Phone Number: 720-723-6477
- Email: kelly.stearns@va.gov
Study Contact Backup
- Name: Meghan C Barnhart
- Phone Number: 720-648-1722
- Email: meghan.barnhart@va.gov
Study Locations
-
-
Colorado
-
Denver, Colorado, United States, 80045
- Recruiting
- VA Rocky Mountain Regional Center
-
Contact:
- Pamela Rice, Ph.D.
- Email: Pamela.Rice@va.gov
-
Principal Investigator:
- Lisa Brenner, Ph.D.
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion criteria
- History of at least one deployment in support of OEF/OIF
- Current diagnosis of PTSD per the Clinician Administered PTSD Scale-5 (CAPS-5)
- Current diagnosis of Functional Bowel Disorder by ROME IV
- CRP level of 1.0 mg/L or above at baseline
- Medical clearance to participate by study providers
- Age between 18 and 60
- Ability to provide informed consent
- Willingness to abstain from probiotic supplements (pills, tablets, oils, foods, etc.) other than the investigational product provided until all study procedures are completed
- Willingness to provide blood and stool samples
Exclusion criteria
- Inability to adequately respond to questions regarding the informed consent procedure
- Currently involved in the criminal justice system as a prisoner or ward of the state
- Non-English speaking
- Current (past month) alcohol or substance abuse or dependence
- Lifetime history of bipolar disorder or psychosis or anxiety disorders (excluding PTSD).
- Consistent (e.g., 5x/week or greater) probiotic supplementation within the last month, including probiotic food products such as yogurt, as determined by phone screen interview and Probiotic Food Check List
- Receiving intravenous, intramuscular, or oral antibiotics within the last month
- Presence of central venous catheters (CVCs)
- Gastrointestinal (GI) barriers as identified by the 2-week run-in period as determined by the study team
- Participation in conflicting interventional research protocol
- Vital signs outside of acceptable range, i.e., blood pressure >160/100, pulse >100
- Use of any of the following drugs within the last 6 months: antifungals, antivirals or antiparasitics (intravenous, intramuscular, or oral); oral, intravenous, intramuscular, or inhaled corticosteroids; cytokines or cytokine inhibitors; methotrexate or immunosuppressive cytotoxic agents
- Acute disease at the time of enrollment (defer sampling until the participant recovers). Acute disease is defined as the presence of a moderate or severe illness with or without fever (e.g., oral temperature >100° F)
- Any medical condition deemed exclusionary by the Principal Investigators
- History of cancer
- Unstable dietary history as determined by the PIs (e.g., major changes in diet during the previous month, where the subject has eliminated or significantly increased a major food group in the diet)
- Positive test for human immunodeficiency virus (HIV), Hepatitis B virus, or Hepatitis C virus
- Any confirmed or suspected condition/state of immunosuppression or immunodeficiency (primary or acquired) including HIV infection, or those receiving immunosuppressive drugs or treatment including antineoplastic therapy, post-transplantation immunosuppressive therapy, and/or radiation therapy
- Major surgery of the GI tract, with the exception of cholecystectomy and appendectomy, in the past five years. Any major bowel resection at any time
- Female who is pregnant or lactating
- Treatment for or suspicion of ever having had toxic shock syndrome
- History of moderate and/or severe traumatic brain injury
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Supplement
8 weeks of dietary augmentation with oral LGG 1.0 x 1010 colony forming units (CFU) once daily (delivered in a size 1 capsule)
|
See arm descriptions
|
Placebo Comparator: Placebo
8 weeks of dietary augmentation with placebo once daily (delivered in a size 1 capsule)
|
See arm descriptions
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Plasma concentration of C-reactive protein (CRP)
Time Frame: Change from basline to directly following the 8 week intervention
|
Blood biomarker of inflammation
|
Change from basline to directly following the 8 week intervention
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
PTSD symptoms per the PTSD Checklist for DSM-5 (PCL-5)
Time Frame: Change from basline to directly following the 8 week intervention
|
PTSD symptoms
|
Change from basline to directly following the 8 week intervention
|
Type and abundance measurement of gut microbiota
Time Frame: Change from basline to directly following the 8 week intervention
|
qRT-PCR and DNA sequencing of the 16S rRNA gene
|
Change from basline to directly following the 8 week intervention
|
Plasma concentration of intestinal permeability
Time Frame: Change from basline to directly following the 8 week intervention
|
fatty acid binding protein 2 and D-amino acid oxidase
|
Change from basline to directly following the 8 week intervention
|
Plasma concentration of inflammatory markers
Time Frame: Change 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
|
Change from basline to directly following the 8 week intervention
|
Biological and psychological stress response
Time Frame: Immediately post-intervention
|
Cyberball
|
Immediately post-intervention
|
Decision-making
Time Frame: Immediately post-intervention
|
Iowa Gambling Test
|
Immediately post-intervention
|
Collaborators and Investigators
Investigators
- Principal Investigator: Lisa Brenner, Ph.D., US Department of Veterans Affairs
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 19-2415
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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