Clinical trial NCT06464952: Microbiome Modulation With Prebiotics in PTSD and Cirrhosis
Official title: Structure and Function of Microbiome Change in Subjects With Cirrhosis and PTSD After Potato Starch or Cellulose Supplementation (RESIST-PTSD)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cirrhosis
PTSD
Keywords: microbiome
prebiotic
gut-brain
liver disease
Lead sponsor: Hunter Holmes Mcguire Veteran Affairs Medical Center
Sponsor class: FED
First posted: 2024-06-18
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: RCT in patients with cirrhosis and PTSD focused on feasibility and safety
Primary purpose: SUPPORTIVE_CARE

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Gut microbiome Alpha Diversity between groups
timeFrame: 8 weeks
Secondary outcomes:
measure: Gut microbiome Alpha Diversity within groups at study end
timeFrame: 8 weeks
measure: Gut microbiome Alpha Diversity within groups at mid-study
timeFrame: 4 weeks
measure: Serum bile acids
timeFrame: 8 weeks
measure: Serum bile acids
timeFrame: 8 weeks
measure: Serum short-chain fatty acid (SCFA) levels
timeFrame: 8 weeks
measure: Stool short-chain fatty acid (SCFA) levels
timeFrame: 8 weeks
measure: Serum short-chain fatty acid (SCFA) levels
timeFrame: 8 weeks
measure: Stool short-chain fatty acid (SCFA) levels
timeFrame: 8 weeks
measure: MELD score change within group
timeFrame: 8 weeks
measure: MELD score change between groups
timeFrame: 8 weeks
measure: Adherence on assigned therapy
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Hunter Holmes McGuire VA Medical Center
state: Virginia
Study officials:
References: