Prebiotics for PTSD and Liver Cirrhosis

(RESIST-PTSD Trial)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Hunter Holmes Mcguire Veteran Affairs Medical Center

Must not be taking: Prebiotics, Probiotics, Antibiotics, others

Disqualifiers: Alcohol abuse, Drug use, Pregnancy, others

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot use prebiotics, probiotics, certain fiber supplements, systemic antibiotics, or anti-diarrheal agents in the 30 days before starting the trial. If you're on treatment for hepatic encephalopathy, you may also need to stop.

What data supports the effectiveness of the treatment Resistant potato starch, Resistant Starch, Dietary Fiber Prebiotics, RS for PTSD and Liver Cirrhosis?

Research shows that resistant starch and prebiotic fibers can improve liver health by positively affecting gut bacteria and reducing liver fat, as seen in studies on liver diseases like non-alcoholic fatty liver disease. Additionally, prebiotics have been shown to increase beneficial gut bacteria and produce health-promoting compounds, which may support overall health. ^{1 2 3 4 5}

Is resistant starch safe for human consumption?

Resistant starch, a type of dietary fiber, has been studied in humans and is generally considered safe. Studies have shown it can improve gastrointestinal symptoms and may have beneficial effects on gut bacteria without significant adverse effects. ^{1 4 6 7 8}

How is the treatment with resistant potato starch unique for PTSD and liver cirrhosis?

Resistant potato starch is unique because it acts as a prebiotic, which means it helps beneficial bacteria grow in the gut. This can improve gut health and reduce inflammation, potentially benefiting conditions like PTSD and liver cirrhosis by targeting the gut-liver-brain axis, which is not a focus of most traditional treatments. ^{1 4 9 10 11}

Research Team

Eligibility Criteria

This trial is for Veterans with PTSD and liver cirrhosis, focusing on those who may have cognitive impairments and altered gut microbiomes. It's not suitable for individuals without these specific conditions or those who cannot safely consume dietary supplements.

Inclusion Criteria

I am older than 18 years.

I am willing and able to follow the study rules and attend all required visits.

Ability to provide informed written consent

Exclusion Criteria

Allergies to any of the ingredients in assigned products

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

Unstable psychiatric illness (psychosis)

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either resistant potato starch or cellulose supplementation to modulate gut microbiome

8 weeks

Regular visits for monitoring and adherence checks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Resistant potato starch (Prebiotic)

Trial Overview The study tests the effects of powdered cellulose and resistant potato starch as prebiotics to improve gut health in patients with both PTSD and cirrhosis. The goal is to see if these natural fibers can positively affect the gut-brain axis.

Participant Groups

Group I: Resistant potato starch Experimental Treatment 1 Intervention

Group II: Cellulose Active Control 1 Intervention

Who Is Running the Clinical Trial?

Hunter Holmes Mcguire Veteran Affairs Medical Center

Lead Sponsor

Trials

37

Recruited

21,600+

Findings from Research

A randomized controlled clinical trial is being conducted to explore the benefits of resistant starch, a prebiotic, for treating metabolic dysfunction-associated steatotic liver disease, which affects nearly one-third of adults worldwide.

The study aims to uncover the underlying mechanisms by which resistant starch may improve liver health in individuals with this prevalent chronic liver condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vive la resistant starch: A potential treatment for metabolic dysfunction-associated steatohepatitis. Zhang, X., Yu, J., Wong, VW.[2023]

A daily intake of 12 g of a prebiotic fiber supplement significantly increased beneficial Bifidobacterium species in the gut microbiome of 20 healthy adults on a low-fiber diet, indicating its efficacy in improving gut health.

The study also found that this prebiotic supplementation led to increased production of health-promoting metabolites, such as indolepropionate, suggesting potential benefits for overall health in individuals struggling to consume enough dietary fiber.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-Omic Analyses Reveal Bifidogenic Effect and Metabolomic Shifts in Healthy Human Cohort Supplemented With a Prebiotic Dietary Fiber Blend. Kang, JW., Tang, X., Walton, CJ., et al.[2022]

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are serious liver conditions linked to metabolic syndrome, and current treatments primarily focus on lifestyle changes, which often prove ineffective.

Emerging research suggests that prebiotic fibers may offer a promising therapeutic approach for NAFLD and NASH by positively altering gut microbiota, reducing body fat, and improving glucose regulation, warranting further clinical trials in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential role of prebiotic fibre for treatment and management of non-alcoholic fatty liver disease and associated obesity and insulin resistance. Parnell, JA., Raman, M., Rioux, KP., et al.[2017]

A feasibility study involving 10 adults showed that daily intake of resistant potato starch (RPS) from day -7 to day 100 after allogeneic hematopoietic stem cell transplantation significantly increased fecal butyrate levels, indicating a positive impact on gut health (P < 0.0001).

The study also found that RPS led to more stable plasma metabolites in participants compared to historical controls, suggesting potential benefits for metabolic health post-transplant, and a phase 2 trial is planned to further investigate its effects on graft-versus-host disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of a dietary intervention to modify gut microbial metabolism in patients with hematopoietic stem cell transplantation. Riwes, MM., Golob, JL., Magenau, J., et al.[2023]

Resistant starch type 2 (RS2) has been shown to positively influence metabolic health by modifying the gut microbiome, as evidenced by consistent findings across 48 studies (13 human and 35 animal) that report increased production of beneficial short-chain fatty acids and specific bacterial taxa enrichment.

Despite the overall positive effects of RS2, significant variability in gut microbiome responses was observed, influenced by factors such as study methodology, host genetics, and baseline microbial composition, highlighting the complexity of dietary interventions targeting gut health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conserved and variable responses of the gut microbiome to resistant starch type 2. Bendiks, ZA., Knudsen, KEB., Keenan, MJ., et al.[2021]

A clinical trial with varying doses of a novel resistant starch blend (RSB) showed that consuming around 5 g of resistant starch daily can improve gastrointestinal symptoms over a period of 6 weeks, particularly reducing diarrhea scores.

Higher doses of the RSB blend were linked to reduced sleep disturbances and changes in gut microbiome composition, specifically increasing beneficial bacteria like Faecalibacterium and Akkermansia, which are associated with better human health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The gastrointestinal and microbiome impact of a resistant starch blend from potato, banana, and apple fibers: A randomized clinical trial using smart caps. Hanes, D., Nowinski, B., Lamb, JJ., et al.[2022]

In a study involving 14 healthy adults, both resistant starch (RS) and wheat bran (WB) significantly increased daily faecal output compared to a low-fibre baseline, with RS increasing output to 164.2 g and WB to 194.5 g.

While both types of fibre improved faecal weight, only wheat bran significantly enhanced faecal consistency, indicating that while RS is effective for increasing output, WB may be better for improving stool quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beneficial effects of resistant starch on laxation in healthy adults. Maki, KC., Sanders, LM., Reeves, MS., et al.[2017]

Resistant starch (both RS2 and RS3) significantly improved the colon flora in mice by increasing beneficial bifidobacteria and decreasing harmful enterobacteria, indicating a positive effect on gut health.

The intake of RS2, particularly at higher concentrations, led to increased production of short-chain fatty acids (SCFAs) and a reduction in the pH of feces and cecum content, suggesting enhanced fermentation and overall digestive health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Influence of resistant starch on colon flora of rats]. He, M., Hong, J., Yang, YX., et al.[2005]

Dietary interventions, particularly the intake of resistant starches (RSs), can help alleviate non-alcoholic fatty liver disease (NAFLD) by improving gut barrier function and reducing inflammation in the gut-liver axis, as suggested by emerging evidence.

RSs promote beneficial changes in gut microbiota and enhance the production of short-chain fatty acids (SCFAs), which support immune-metabolic balance and may serve as a promising alternative therapy for NAFLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amelioratory Effect of Resistant Starch on Non-alcoholic Fatty Liver Disease via the Gut-Liver Axis. Zhu, W., Zhou, Y., Tsao, R., et al.[2022]

In a study involving aged mice fed a high-fat diet, resistant starch (RS) from pulses like lentils and chickpeas significantly improved gut health by modulating the gut microbiome and reducing gut permeability, particularly enhancing tight-junction protein expression.

The supplementation of RS led to a decrease in harmful bacteria and an increase in beneficial short-chain fatty acid-producing bacteria, suggesting that dietary pulses could serve as effective prebiotics to promote gut and metabolic health in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prebiotic mechanisms of resistant starches from dietary beans and pulses on gut microbiome and metabolic health in a humanized murine model of aging. Kadyan, S., Park, G., Singh, P., et al.[2023]

In a study of 93 male veterans with cirrhosis, those with combat-related PTSD exhibited poorer cognitive performance and lower gut microbial diversity, indicating a potential link between gut health and cognitive function.

PTSD was associated with higher levels of harmful bacteria (pathobionts) like Enterococcus and Escherichia/Shigella, and lower levels of beneficial bacteria, suggesting that targeting gut microbiota may offer a new therapeutic approach for improving cognitive outcomes in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Posttraumatic stress disorder is associated with altered gut microbiota that modulates cognitive performance in veterans with cirrhosis. Bajaj, JS., Sikaroodi, M., Fagan, A., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Vive la resistant starch: A potential treatment for metabolic dysfunction-associated steatohepatitis. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Multi-Omic Analyses Reveal Bifidogenic Effect and Metabolomic Shifts in Healthy Human Cohort Supplemented With a Prebiotic Dietary Fiber Blend. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

The potential role of prebiotic fibre for treatment and management of non-alcoholic fatty liver disease and associated obesity and insulin resistance. [2017]

4. United States pubmed.ncbi.nlm.nih.gov

Feasibility of a dietary intervention to modify gut microbial metabolism in patients with hematopoietic stem cell transplantation. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Conserved and variable responses of the gut microbiome to resistant starch type 2. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

The gastrointestinal and microbiome impact of a resistant starch blend from potato, banana, and apple fibers: A randomized clinical trial using smart caps. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Beneficial effects of resistant starch on laxation in healthy adults. [2017]

8. China pubmed.ncbi.nlm.nih.gov

[Influence of resistant starch on colon flora of rats]. [2005]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Amelioratory Effect of Resistant Starch on Non-alcoholic Fatty Liver Disease via the Gut-Liver Axis. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Prebiotic mechanisms of resistant starches from dietary beans and pulses on gut microbiome and metabolic health in a humanized murine model of aging. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Posttraumatic stress disorder is associated with altered gut microbiota that modulates cognitive performance in veterans with cirrhosis. [2020]