Microbiome Modulation With Prebiotics in PTSD and Cirrhosis

PTSD Clinical Trial

— RESIST-PTSD  

Official title:

Structure and Function of Microbiome Change in Subjects With Cirrhosis and PTSD After Potato Starch or Cellulose Supplementation (RESIST-PTSD)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06464952
• Other study ID #: BAJAJ0036
• Status: Recruiting
• Phase: N/A
• Start date: June 25, 2024
• Est. completion date: September 25, 2025

Study information

• Verified date: June 2024
• Source: Hunter Holmes Mcguire Veteran Affairs Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Despite medical advancements, PTSD remains a major issue in Veterans1. Current treatment strategies have relatively poor adherence. In patients with PTSD and cirrhosis, there is greater cognitive impairment as well as changes in gut microbiome structure and function2,3. In addition, when there is concomitant cirrhosis, medication-related treatment options become even narrower from a safety and tolerability perspective and cognitive issues pertaining to cirrhosis could impact participation3. Changes in gut microbiome in Veterans with cirrhosis and PTSD compared to those with cirrhosis without PTSD is characterized by a greater relative expression of pathobionts and reduction in stool microbiome diversity with reduction in bacteria that produce beneficial short chain fatty acids (SCFA)2. Modulation of the gut microbiome in patients with cirrhosis and PTSD may be an important therapeutic target. In prior studies with cirrhosis alone, microbial modulation using diet, antibiotics such as rifaximin, probiotics, and fecal microbiota transplant have improved gut microbial diversity and clinical outcomes in some cases4,5. In patients with cirrhosis without PTSD and in patients with PTSD without cirrhosis there is emerging evidence regarding prebiotics and other forms of gut microbial modulation.

Prebiotics are such an example6. Prebiotics are natural fibers derived from carbohydrates and can be beneficial to gut microbiota (good bacteria in the gut)6. Resistant starches (RS) are dietary fiber prebiotics found naturally in many foods including potatoes, plantains, and legumes6,7. In addition to being highly accessible, RS have been shown to be well tolerated with few adverse reactions. While no studies of RS exist in PTSD + cirrhosis patients, a meta-analysis of RS in IBD has shown RS to be an effective treatment in both animal and clinical studies where improvements in clinical remission and reduced mucosal damage were found7. However, there is insufficient data regarding patients with PTSD and cirrhosis regarding gut microbial structure and function modulation with dietary supplements such as resistant starches. These starches can improve SCFA production in elderly subjects, which could in turn affect the gut-brain axis favorably8.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: September 25, 2025
• Est. primary completion date: June 25, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age >18 years

2. Ability to provide informed written consent

3. Cirrhosis diagnosis

4. Willing to comply with all study procedures and be available for the duration of the study.

5. Ability to take oral medication.

6. Willing to provide study-related samples

7. Meeting the PCL-5 definition of PTSD and have a chart diagnosis of PTSD made by a mental health provider

Exclusion Criteria:

1. Known SARS-CoV-2 infection in the last 60 days using medical records

2. Subjects identified as, or appearing to, lack consent capacity

3. Alcohol abuse (greater than 14 drinks per week for men and 7 drinks per week for women)

4. Active illicit drug use (marijuana is allowed)

5. Use of investigational drugs, biologics, or devices within 30 days prior to randomization.

6. Individuals who are pregnant, lactating or planning on becoming pregnant during the study

7. Diagnosed inflammatory bowel disease, Crohn's disease, or Celiac disease

8. Unstable psychiatric illness (psychosis)

9. Previous gastrointestinal surgery (colorectal surgery, gastric bypass, intestinal resection)

10. Use of other prebiotics, probiotics (including yogurt containing live probiotics), postbiotics, or other fiber supplements in the last 30 days

11. Systemic antibiotics in the last 30 days

12. Fecal microbiota transplant in the last 30 days

13. Active dysphagia

14. Allergies to any of the ingredients in assigned products

15. Use of anti-diarrheal agents, stool softeners, or immunomodulatory medications in the last 30 days.

16. On treatment for hepatic encephalopathy.

17. Any other factor, condition, or medication not listed above the Investigators believe will affect the response in the gut or the interpretation of results.

Related Conditions & MeSH terms

• Cirrhosis
• Fibrosis
• Liver Cirrhosis
• PTSD

Intervention

Dietary Supplement:
• Resistant potato starch
Prebiotic
• Powdered cellulose
Active comparator

Locations

Country	Name	City	State
United States	Hunter Holmes McGuire VA Medical Center	Richmond	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Hunter Holmes Mcguire Veteran Affairs Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gut microbiome Alpha Diversity between groups	Shannon diversity at end of interventions between both groups	8 weeks
Secondary	Gut microbiome Alpha Diversity within groups at study end	Shannon diversity at end of interventions within each group	8 weeks
Secondary	Gut microbiome Alpha Diversity within groups at mid-study	Shannon diversity at mid-study within each group	4 weeks
Secondary	Serum bile acids	Bile acid levels in serum at end of study between groups	8 weeks
Secondary	Serum bile acids	Bile acid levels in serum at end of study within groups compared to baseline	8 weeks
Secondary	Serum short-chain fatty acid (SCFA) levels	SCFA levels in serum at end of study between groups	8 weeks
Secondary	Stool short-chain fatty acid (SCFA) levels	SCFA levels in stool at end of study between groups	8 weeks
Secondary	Serum short-chain fatty acid (SCFA) levels	SCFA levels in serum at end of study within groups compared to baseline	8 weeks
Secondary	Stool short-chain fatty acid (SCFA) levels	SCFA levels in stool at end of study within groups compared to baseline	8 weeks
Secondary	MELD score change within group	MELD score within groups compared to baseline	8 weeks
Secondary	MELD score change between groups	MELD score between groups	8 weeks
Secondary	Adherence on assigned therapy	Proportion of assigned therapy taken during the entire study between groups (%)	8 weeks