Microbiome Modulation With Prebiotics in PTSD and Cirrhosis
NCT Number: NCT06464952
Acronym: RESIST-PTSD
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Cirrhosis|PTSD
Interventions: DIETARY_SUPPLEMENT: Resistant potato starch|DIETARY_SUPPLEMENT: Powdered cellulose
Sponsor: Hunter Holmes Mcguire Veteran Affairs Medical Center
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 30
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: DOUBLE (PARTICIPANT, OUTCOMES_ASSESSOR)|Primary Purpose: SUPPORTIVE_CARE
Start Date: 2024-07-31
Completion Date: 2025-09-25
Locations: Hunter Holmes McGuire VA Medical Center, Richmond, Virginia, 23249, United States

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.

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