Probiotics for PTSD

Overseen By Kelly A Stearns-Yoder

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: VA Eastern Colorado Health Care System

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

Disqualifiers: Alcohol, Substance abuse, Bipolar, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the probiotic Lactobacillus rhamnosus GG can reduce PTSD symptoms, particularly in Veterans. Researchers believe inflammation might worsen PTSD symptoms, so they are testing if this probiotic can balance the body's response. Participants will receive either the probiotic or a placebo for eight weeks. Those diagnosed with PTSD and a bowel disorder, who have been deployed in support of OEF/OIF, may qualify for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that Lactobacillus rhamnosus GG is likely to be safe for humans?

Research shows that Lactobacillus rhamnosus GG (LGG), the probiotic under study, is generally safe for people. Studies have found that LGG does not usually cause serious side effects. This probiotic is known to help reduce inflammation, which is important for treating PTSD symptoms. While any treatment can have some side effects, current evidence suggests that LGG is a safe option to explore for its potential benefits in PTSD. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for PTSD?

Most treatments for PTSD, like psychotherapy and medications such as SSRIs (selective serotonin reuptake inhibitors), work by altering brain chemistry or behavior patterns over time. However, Lactobacillus rhamnosus GG (LGG) offers a fresh perspective by targeting the gut-brain axis, which is thought to influence mental health. This probiotic might help balance gut bacteria, potentially reducing stress and anxiety in a way traditional treatments don’t. Researchers are excited about LGG because it represents a novel, potentially gentler approach to managing PTSD symptoms without the side effects often associated with psychiatric medications.

What evidence suggests that Lactobacillus rhamnosus GG could be an effective treatment for PTSD?

This trial will compare the effects of Lactobacillus rhamnosus GG (LGG) with a placebo in participants with PTSD. Research has shown that LGG, a type of beneficial bacteria, might help reduce inflammation, which is believed to affect PTSD symptoms. Studies have found that LGG can maintain gut bacteria balance, potentially assisting in managing stress and reducing PTSD symptoms. Early research suggests that LGG helps the brain manage inflammation more effectively. Although data remains limited, these early results are promising for using LGG as a treatment for PTSD. ^{1 5 6 7 8}

Who Is on the Research Team?

Lisa Brenner, Ph.D.

Principal Investigator

US Department of Veterans Affairs

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

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

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.

How Is the Trial Designed?

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)

Lactobacillus rhamnosus GG (LGG; ATCC strain 53103; CRMTS #11272; PTS #3766) is already approved in European Union, United States for the following indications:

Approved in European Union as Lactobacillus rhamnosus GG for:

• Acute gastroenteritis in children
• Adjunct to rehydration therapy

Approved in United States as Lactobacillus rhamnosus GG for:

• Investigational use for PTSD symptoms
• Adjunct to rehydration therapy for acute gastroenteritis

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35812820/

A randomized placebo-controlled trial of an ... - PubMed This is a Phase IIa trial of LGG for United States military Veterans with PTSD, using a longitudinal, double-blind, randomized placebo-controlled design.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04150380

NCT04150380 | Probiotic (LGG) for Veterans With PTSD In this study, the investigators will investigate the effects of an 8-week oral administration of an immunoregulatory probiotic, Lactobacillus rhamnosus GG (LGG ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2451865422000771

Rationale, design, and methods: A randomized placebo ... This is a Phase IIa trial of LGG for United States military Veterans with PTSD, using a longitudinal, double-blind, randomized placebo-controlled design.

4. uchealth.org uchealth.org/today/gut-health-could-be-key-for-healping-some-veterans-with-ptsd/

Can improved gut health help veterans with PTSD? The idea is that the strain Lactobacillus rhamnosus GG (LGG) could help to maintain a healthy microbial balance in the gut. A healthy mix of ...

5. karger.com karger.com/nim/article/32/1/94/922633/Effects-of-Oral-Administration-of-the-Probiotic

Effects of Oral Administration of the Probiotic Lactobacillus ... Collectively, our results suggest that administration of LGG may promote a physiological resilience to neuroinflammatory events by modulating ...

6. withpower.com withpower.com/trial/phase-3-stress-disorders-post-traumatic-7-2020-20a9f?lat=36.65114&lng=-97.3517

Probiotics for PTSD · Info for Participants 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, ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0028390823000084

Alleviating anxiety and taming trauma: Novel ... Up-to-date overview on developing new medications including candidates with novel bioloigical targets for the treatment of anxiety disorders and PTSD.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10372846/

Alleviating anxiety and taming trauma - PubMed Central - NIH LGG ATCC strain 53103 CRMTS #11272 PTS #3766 ... A randomized dose-ranging study of neuropeptide Y in patients with posttraumatic stress disorder.