Post Traumatic Stress DisorderPhase 2NCT04150380
Probiotic (LGG) for Veterans With PTSD
A Phase 2 study testing Lactobacillus rhamnosus GG (LGG; ATCC strain 53103; CRMTS #11272; PTS #3766) in people with Post Traumatic Stress Disorder and Inflammation, run by VA Eastern Colorado Health Care System at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Post Traumatic Stress Disorder, Inflammation
- What is being tested?
- Lactobacillus rhamnosus GG (LGG; ATCC strain 53103; CRMTS #11272; PTS #3766)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 383 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Aug 2020to 31 Dec 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Rocky Mountain Regional Center
Denver, Colorado, 80045
About this study
Official title: Biological Signature and Safety of an Immunomodulatory Probiotic Intervention for Veterans With PTSD
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.
Read the 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.
- Conditions
- Post Traumatic Stress Disorder, Inflammation
- Being tested
- Lactobacillus rhamnosus GG (LGG; ATCC strain 53103; CRMTS #11272; PTS #3766), Placebo
- Medical subject headings
- Stress Disorders, Post-Traumatic, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lactobacillus rhamnosus GG (LGG; ATCC strain 53103; CRMTS #11272; PTS #3766)Biological
See arm descriptions
PlaceboOther
See arm descriptions
| Study group | Role | What they receive |
|---|---|---|
| Supplement | Experimental | 8 weeks of dietary augmentation with oral LGG 1.0 x 1010 colony forming units (CFU) once daily (delivered in a size 1 capsule) Receives: Biological: Lactobacillus rhamnosus GG (LGG; ATCC strain 53103; CRMTS #11272; PTS #3766) |
| Placebo | Placebo comparator | 8 weeks of dietary augmentation with placebo once daily (delivered in a size 1 capsule) Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma concentration of C-reactive protein (CRP)
Blood biomarker of inflammation
Measured: Change from basline to directly following the 8 week intervention
Secondary outcomes (6)
PTSD symptoms per the PTSD Checklist for DSM-5 (PCL-5)
PTSD symptoms
Measured: Change from basline to directly following the 8 week intervention
Type and abundance measurement of gut microbiota
qRT-PCR and DNA sequencing of the 16S rRNA gene
Measured: Change from basline to directly following the 8 week intervention
Plasma concentration of intestinal permeability
fatty acid binding protein 2 and D-amino acid oxidase
Measured: Change from basline to directly following the 8 week intervention
Plasma concentration of inflammatory markers
IL-10, IL-4, IL-6, IL-8, IFNy, IL-1a, IL-1b, and IL-12p70
Measured: Change from basline to directly following the 8 week intervention
Biological and psychological stress response
Cyberball
Measured: Immediately post-intervention
Decision-making
Iowa Gambling Test
Measured: Immediately post-intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2019
- Study start24 Aug 2020
- Primary completion31 Dec 2025
- Study completion31 Dec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post Traumatic Stress DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- longitudinal, double blind, randomized placebo-controlled design
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 383 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Eastern Colorado Health Care System
- Sponsor type
- US federal agency
- Collaborators
- University of Colorado, Denver, University of Colorado, Boulder
- Responsible party
- Principal investigator, Lisa Brenner, VA Eastern Colorado Health Care System
- Investigators
- Lisa Brenner, Ph.D., Principal investigator, US Department of Veterans Affairs
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04150380
- Sponsor's protocol ID
- 19-2415
- Status last verified
- Mar 2026
- First submitted
- 18 Oct 2019
- Last updated
- 24 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biological Signature and Safety of an Immunomodulatory Probiotic Intervention for Veterans With PTSD
- ClinicalTrials.gov ID
- NCT04150380
- Acronym / sponsor ID
- 19-2415
- Conditions
- Post Traumatic Stress Disorder, Inflammation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 383 participants (actual)
- Lead sponsor
- VA Eastern Colorado Health Care SystemUS federal agency
- Collaborators
- University of Colorado, Denver, University of Colorado, Boulder
- Study start
- 24 Aug 2020 (actual)
- Primary completion
- 31 Dec 2025 (actual)
- Study completion
- 31 Dec 2025 (actual)
- First posted
- 4 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- longitudinal, double blind, randomized placebo-controlled design
| Arm | Type | Receives |
|---|---|---|
| Supplement | Experimental | Biological: Lactobacillus 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) |
| Placebo | Placebo comparator | Other: Placebo8 weeks of dietary augmentation with placebo once daily (delivered in a size 1 capsule) |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (22 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lactobacillus rhamnosus GG (LGG; ATCC strain 53103; CRMTS #11272; PTS #3766)See arm descriptions | Biological | Supplement |
| PlaceboSee arm descriptions | Other | Placebo |
Primary outcome
Plasma concentration of C-reactive protein (CRP)
Time frame: Change from basline to directly following the 8 week intervention
Blood biomarker of inflammation
6 secondary outcomes
PTSD symptoms per the PTSD Checklist for DSM-5 (PCL-5)
Time frame: 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
Plasma concentration of intestinal permeability
Time frame: 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
Biological and psychological stress response
Time frame: Immediately post-intervention
Decision-making
Time frame: Immediately post-intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lisa Brenner, Ph.D. principal investigator
US Department of Veterans Affairs
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lactobacillus rhamnosus GG (LGG; ATCC strain 53103; CRMTS #11272; PTS #3766) in people with Post Traumatic Stress Disorder and Inflammation, run by VA Eastern Colorado Health Care System at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma concentration of C-reactive protein (CRP) (time frame: Change from basline to directly following the 8 week intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2026.