Fecal Microbiota Transplant for Hepatic Encephalopathy

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must be taking: Lactulose, Rifaximin

Must not be taking: Immunosuppressives, Sedatives

Disqualifiers: Current infection, Alcohol use, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for hepatic encephalopathy, a brain condition causing confusion in people with advanced liver disease. The study will determine if oral capsules containing healthy gut bacteria, known as Fecal Microbiota Transplant (FMT) oral capsules, improve brain function more effectively than placebo capsules. Suitable participants should have advanced liver disease with previous episodes of severe confusion and should not be expecting a liver transplant soon. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be compliant with lactulose and rifaximin treatment. If you are on unstable doses of opiates, benzodiazepines, or other sedating medications, you may not be eligible.

Is there any evidence suggesting that Fecal Microbiota Transplant (FMT) is likely to be safe for humans?

Research has shown that fecal microbiota transplant (FMT), which involves transferring healthy bacteria into another person's gut, is safe for people with liver problems. Studies have found no serious side effects from this treatment. The safety remains consistent regardless of the dose, method of delivery, or donor. FMT has also been safely used to treat other conditions, such as recurrent Clostridium difficile, a gut infection. Overall, FMT appears to be a well-tolerated option for those with liver-related issues, with no reports of major negative effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for hepatic encephalopathy, which often include lactulose and rifaximin to reduce toxins in the blood, the Fecal Microbiota Transplant (FMT) oral capsules work by restoring the gut's healthy bacteria balance. This treatment is exciting because it targets the gut microbiome directly, potentially offering a more natural and holistic way to manage the condition. Additionally, FMT is administered through convenient oral capsules, making it a less invasive option compared to traditional methods. Researchers are hopeful that by addressing the root cause in the gut, FMT could improve symptoms more effectively than current therapies.

What evidence suggests that Fecal Microbiota Transplant might be an effective treatment for hepatic encephalopathy?

Research has shown that fecal microbiota transplant (FMT) can help treat hepatic encephalopathy, a condition causing confusion in people with liver disease. Studies have found that FMT is safe and can reduce the recurrence of this condition. In this trial, participants will receive FMT oral capsules, which have shown promise in improving brain function by altering gut bacteria. One study discovered that various types of FMT are effective, with fresh stool being the most effective. Another study observed significant improvements in patients' cognitive abilities after FMT. Early data suggest that FMT could be a promising method to enhance brain function. ^{1 2 3 6 7}

Who Is on the Research Team?

Raymond Chung, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for patients with advanced liver disease who've had at least one episode of hepatic encephalopathy (confusion due to liver problems) but are stable on current treatments. They must not have certain other health issues, recent drug or alcohol use, or be expecting a liver transplant soon.

Inclusion Criteria

You have to take lactulose and rifaximin regularly as prescribed by your doctor.

You have a history of a specific type of brain problem called hepatic encephalopathy, caused by certain medical conditions or events.

You have been diagnosed with cirrhosis based on tests done by a liver doctor.

Exclusion Criteria

Your blood tests show very high or very low levels of certain substances: creatinine, hemoglobin, sodium, calcium, or potassium.

You have tested positive for C. difficile.

You have had a previous case of spontaneous bacterial peritonitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pilot Study

10-patient open-label pilot study to identify efficacious stool donors

Not specified

Treatment

Participants receive 5 doses of oral FMT capsules or placebo over 21 days

3 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Fecal Microbiota Transplant (FMT) oral capsules
• Placebo oral capsule

Trial Overview The study tests if swallowing capsules containing healthy stool bacteria can improve brain function in liver disease patients compared to placebo capsules. It's a randomized controlled trial, meaning participants are randomly assigned to receive either the real treatment or a placebo.

How Is the Trial Designed?

Group I: Fecal Microbiota Transplant (FMT) oral capsules Experimental Treatment 1 Intervention

Subjects will receive 15 oral capsules of FMT on days 1, 2, 7, 14, and 21.

Group II: Placebo capsules Placebo Group 1 Intervention

Subjects will receive placebo capsules on the same schedule as the experimental arm (days 1, 2, 7, 14, and 21).

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Center for Microbiome Informatics and Therapeutics

Collaborator

Trials

1

Recruited

30+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35384391/

Fecal microbiota transplant improves cognition in hepatic ... Early data suggest fecal microbiota transplant (FMT) may treat hepatic encephalopathy (HE). Optimal FMT donor and recipient characteristics ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0168827825000054

Microbiota transplant for hepatic encephalopathy in cirrhosis FMT was safe, with no FMT-related SAEs/AEs reported. Overall SAEs (p = 0.96) or death (p = 1.0) were similar. There were significant differences in HE ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10835490/

Role of fecal microbiota transplant in management ... The efficacy of lyophilized stool (78%) was significantly lower compared to fresh fecal preparation (100%), but equally effective compared to frozen stool (83%) ...

4. journal-of-hepatology.eu journal-of-hepatology.eu/article/S0168-8278(25)00005-4/fulltext

Microbiota transplant for hepatic encephalopathy in cirrhosis We conclude in this randomized, double-blind, placebo-controlled, dose-ranging clinical trial that FMT is safe and associated with lower rates of HE recurrence ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03420482

Fecal Microbiota Transplant As Treatment of Hepatic ... The primary outcome is change in neurological function after FMT. The main secondary outcome is change in microbiome composition after FMT. This study could ...

6. gastrojournal.org gastrojournal.org/article/S0016-5085(19)30093-9/fulltext

Long-term Outcomes of Fecal Microbiota Transplantation in ... In recurrent Clostridium difficile, a single FMT has sustained cure rates of greater than 80% with a tolerable long-term safety profile.

7. healio.com healio.com/news/gastroenterology/20250219/fmt-safe-linked-to-reduced-hepatic-encephalopathy-recurrence-in-patients-with-cirrhosis

FMT safe, linked to reduced hepatic encephalopathy ... Fecal microbiota transplant, regardless of dose or route, was safe and associated with reduced hepatic encephalopathy recurrence among patients with cirrhosis.