Microbiome Modulation With Prebiotics in PTSD and Cirrhosis (RESIST-PTSD)

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

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.

Study Overview

• Status: Recruiting
• Conditions: PTSD; Cirrhosis
• Intervention / Treatment: Dietary supplement: Resistant potato starch; Dietary supplement: Powdered cellulose

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23249
      • Recruiting
      • Hunter Holmes McGuire VA Medical Center
      • Contact: Jasmohan S Bajaj, MD; Phone Number: 804-675-5021; Email: jsbajaj@vcu.edu
      • Principal Investigator: Jasmohan S Bajaj, MD, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Resistant potato starch	Dietary supplement: Resistant potato starch; Prebiotic
Active Comparator: Cellulose	Dietary supplement: Powdered cellulose; Active comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut microbiome Alpha Diversity between groups	Shannon diversity at end of interventions between both groups	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Hunter Holmes Mcguire Veteran Affairs Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2024
• Primary Completion (Estimated): June 25, 2027
• Study Completion (Estimated): September 25, 2027

Study Registration Dates

• First Submitted: June 13, 2024
• First Submitted That Met QC Criteria: June 13, 2024
• First Posted (Actual): June 18, 2024

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 3, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: prebiotic; microbiome; liver disease; gut-brain
• Additional Relevant MeSH Terms: Trauma and Stressor Related Disorders; Mental Disorders; Pathologic Processes; Digestive System Diseases; Stress Disorders, Traumatic; Pathological Conditions, Signs and Symptoms; Fibrosis; Liver Diseases; Stress Disorders, Post-Traumatic
• Other Study ID Numbers: BAJAJ0036

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No