Probiotics for PTSD

Overseen by Lisa Brenner, Ph.D.

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: VA Eastern Colorado Health Care System

Must not be taking: Antifungals, Antivirals, Antiparasitics, others

Disqualifiers: Alcohol, Substance abuse, Bipolar, others

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial investigates using a beneficial bacteria called Lactobacillus rhamnosus GG (LGG) to help U.S. military Veterans with PTSD who do not respond well to traditional treatments. The probiotic aims to reduce inflammation in the body and brain, which is a common issue in PTSD. By balancing gut bacteria, it may improve PTSD symptoms and overall stress response. Lactobacillus rhamnosus GG (LGG) has shown several beneficial effects, including improved insulin sensitivity and anti-inflammatory properties.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use certain drugs like antifungals, antivirals, corticosteroids, or immunosuppressive agents within the last 6 months. You also need to avoid probiotic supplements other than the one provided in the study.

What data supports the effectiveness of the treatment Lactobacillus rhamnosus GG for PTSD?

Lactobacillus rhamnosus GG is known for its health benefits, including reducing inflammation, which is a key factor in PTSD. Although it has been used for other conditions like diarrhea, its potential to lower inflammation might help with PTSD symptoms. ^{1 2 3 4 5}

How is the treatment Lactobacillus rhamnosus GG (LGG) unique for PTSD?

Lactobacillus rhamnosus GG (LGG) is unique for PTSD as it is a probiotic that aims to reduce inflammation, which is thought to contribute to PTSD symptoms, offering an alternative to conventional medications and psychotherapy. ^{1 2 6 7 8}

Research Team

Lisa Brenner, Ph.D.

Principal Investigator

US Department of Veterans Affairs

Eligibility Criteria

This trial is for Veterans aged 18-60 with PTSD who have served in OEF/OIF, can provide blood and stool samples, and are not taking other probiotics. They must have a history of inflammation (CRP level ≥1.0 mg/L) and be medically cleared to participate. Exclusions include non-English speakers, recent antibiotic use, immunodeficiency conditions, certain GI surgeries or barriers, unstable diets, substance abuse issues, pregnancy/lactation among women.

Inclusion Criteria

I have been diagnosed with a Functional Bowel Disorder.

History of at least one deployment in support of OEF/OIF

I am willing to give blood and stool samples for the study.

Exclusion Criteria

I haven't taken antifungals, antivirals, steroids, or immunosuppressants in the last 6 months.

Gastrointestinal (GI) barriers as identified by the 2-week run-in period as determined by the study team

I have had cancer in the past.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 8 weeks of dietary augmentation with oral LGG or placebo

8 weeks

Weekly visits (in-person or virtual) for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Lactobacillus rhamnosus GG (LGG; ATCC strain 53103; CRMTS #11272; PTS #3766) (Probiotic)
• Placebo (Other)

Trial Overview The study tests whether the probiotic Lactobacillus rhamnosus GG (LGG) can reduce chronic PTSD symptoms by decreasing body and brain inflammation. Participants will either receive LGG or a placebo while researchers monitor changes in biomarkers of inflammation, gut microbiota composition, stress response decision making.

Participant Groups

Group I: Supplement Experimental Treatment 1 Intervention

8 weeks of dietary augmentation with oral LGG 1.0 x 1010 colony forming units (CFU) once daily (delivered in a size 1 capsule)

Group II: Placebo Placebo Group 1 Intervention

8 weeks of dietary augmentation with placebo once daily (delivered in a size 1 capsule)

Who Is Running the Clinical Trial?

VA Eastern Colorado Health Care System

Lead Sponsor

Trials

55

Recruited

26,200+

University of Colorado, Denver

Collaborator

Trials

1,842

Recruited

3,028,000+

University of Colorado, Boulder

Collaborator

Trials

128

Recruited

29,600+

Findings from Research

A new real-time PCR assay was developed to specifically identify Lactobacillus rhamnosus GG, achieving 100% true positive and 0% false positive results across 22 target samples, ensuring accurate identification of this important probiotic strain.

The assay demonstrated high sensitivity and efficiency, with a Limit of Detection of 0.001 ng and excellent reproducibility, making it suitable for onsite testing in the probiotic supply chain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Validated Real-Time PCR Method for the Specific Identification of Probiotic Strain Lactobacillus rhamnosus GG (ATCC 53103). Shehata, HR., Newmaster, SG.[2022]

This Phase IIa randomized placebo-controlled trial is investigating the use of the probiotic Lactobacillus rhamnosus GG (LGG) to reduce inflammation in military Veterans with PTSD, focusing on its potential to alleviate symptoms associated with the disorder.

The study aims to measure the effectiveness of LGG by assessing changes in plasma levels of high-sensitivity C-reactive protein, a marker of inflammation, highlighting the role of inflammation in PTSD and the need for alternative treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale, design, and methods: A randomized placebo-controlled trial of an immunomodulatory probiotic intervention for Veterans with PTSD. Brenner, LA., Stearns-Yoder, KA., Stamper, CE., et al.[2022]

Lactobacillus rhamnosus GG (LGG) significantly reduces the duration of acute diarrhea in children, with a mean difference of -24.02 hours compared to control groups, based on a meta-analysis of 19 randomized controlled trials.

Higher doses of LGG (≥ 10^10 CFU per day) are particularly effective, especially in cases of rotavirus-induced diarrhea, suggesting that early intervention with high-dose LGG can lead to quicker recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Lactobacillus rhamnosus GG in treatment of acute pediatric diarrhea: A systematic review with meta-analysis. Li, YT., Xu, H., Ye, JZ., et al.[2022]

Lactobacillus rhamnosus GG (LGG) was found to significantly reduce the proliferation of T and B cells and lower levels of interferon-gamma in mice with an autoimmune response induced by Campylobacter jejuni, suggesting an immune-suppressive effect.

In this study involving 40 ICR mice, LGG did not significantly change the levels of ds-DNA antibodies compared to the model group, indicating that while it can inhibit certain immune responses, it may not affect all aspects of the autoimmune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of Lactobacillus rhamnosus GG on immune response: experiment with autoimmune mice induced by Campylobacter jejuni]. Zhang, Q., Chen, QY.[2020]

Lactobacillus rhamnosus GG (Lactobacillus GG) effectively induces the production of nitric oxide (NO) through the inducible nitric oxide synthase (iNOS) pathway, which is similar to the mechanisms triggered by lipopolysaccharide (LPS) and lipoteichoic acid (LTA).

The study identified that various inhibitors, including those targeting protein synthesis and specific signaling pathways, can significantly reduce NO production induced by Lactobacillus GG, highlighting the complexity of its immunostimulatory effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Signalling mechanisms involved in the induction of inducible nitric oxide synthase by Lactobacillus rhamnosus GG, endotoxin, and lipoteichoic acid. Korhonen, R., Korpela, R., Moilanen, E.[2022]

Lactobacillus rhamnosus GR-1 significantly induces the production of granulocyte colony-stimulating factor (G-CSF) in macrophages, with levels increasing over 60-fold, while not affecting other pro-inflammatory cytokines like IL-1 and TNF-α.

The signaling mechanism for G-CSF production involves TLR2-dependent pathways, specifically activating extracellular regulated kinases and p38, but not c-Jun N-terminal kinases, highlighting GR-1's unique immunomodulatory effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preferential production of G-CSF by a protein-like Lactobacillus rhamnosus GR-1 secretory factor through activating TLR2-dependent signaling events without activation of JNKs. Meshkibaf, S., Fritz, J., Gottschalk, M., et al.[2022]

The study evaluated two PCR-based methods for accurately identifying Lactobacillus rhamnosus strain GG, finding that the phage-related gene-targeting system is effective for distinguishing this strain from others.

The results showed that while some strains were genetically distinguishable from strain GG, others were very similar, indicating that the phage-related system can detect both the original strain and its derivatives, enhancing strain-specific identification.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of strain-specific primers for identification of Lactobacillus rhamnosus GG. Endo, A., Aakko, J., Salminen, S.[2022]

The metabolites of the probiotic strain Lactobacillus rhamnosus GG significantly reduced the infection activity of enteroviruses (Coxsackie B-5 and ECNO-21) in cell cultures, showing a decrease of 1.5-1.7 times after 24 hours and up to 5.7 times after 96 hours.

The maximum tolerated dose of L. rhamnosus GG metabolites was determined to be 0.3 mg/ml, which effectively decreased the viral titer in various cell lines, indicating potential for therapeutic use against enteroviral infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study of anti-virus actions of metabolites of lactobacteria. Kalinichenko, SV., Melentyevа, KV., Manee, H., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

A Validated Real-Time PCR Method for the Specific Identification of Probiotic Strain Lactobacillus rhamnosus GG (ATCC 53103). [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Rationale, design, and methods: A randomized placebo-controlled trial of an immunomodulatory probiotic intervention for Veterans with PTSD. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Efficacy of Lactobacillus rhamnosus GG in treatment of acute pediatric diarrhea: A systematic review with meta-analysis. [2022]

4. China pubmed.ncbi.nlm.nih.gov

[Effect of Lactobacillus rhamnosus GG on immune response: experiment with autoimmune mice induced by Campylobacter jejuni]. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Signalling mechanisms involved in the induction of inducible nitric oxide synthase by Lactobacillus rhamnosus GG, endotoxin, and lipoteichoic acid. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Preferential production of G-CSF by a protein-like Lactobacillus rhamnosus GR-1 secretory factor through activating TLR2-dependent signaling events without activation of JNKs. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Evaluation of strain-specific primers for identification of Lactobacillus rhamnosus GG. [2022]

8. Poland pubmed.ncbi.nlm.nih.gov

Study of anti-virus actions of metabolites of lactobacteria. [2022]