Fecal Microbiota Transplant for Alcoholic Hepatitis

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Prasun Kumar Jalal

Disqualifiers: Non-alcoholic liver diseases, Cancer, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single center, randomized, parallel assignment, and double-blind placebo-controlled pilot study to characterize the intestinal microbiome in patients with severe Alcoholic Hepatitis (SAH) and evaluate the safety and the trends in improvement of diversity of intestinal microbiome following administration of lyophilized capsules containing microbiota suspension from well screened health donors. The study aims to enroll 50 patients with SAH who will be randomly assigned in 1:1 where 25 patients will be assigned to receive orally administered lyophilized PRIM-DJ2727 and Standard of Care (SOC) and the other 25 patients will be assigned to receive placebo and SOC for 4 weeks.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Fecal Microbiota Transplantation (FMT) for Alcoholic Hepatitis?

Research suggests that Fecal Microbiota Transplantation (FMT) can improve survival and disease severity in patients with severe alcoholic hepatitis, especially those who do not respond to standard steroid treatments. Initial human trials have shown benefits in improving clinical outcomes and survival rates, and FMT may become a standard treatment option in the future. ^{1 2 3 4 5}

Is fecal microbiota transplantation (FMT) safe for humans?

FMT has been shown to be generally safe in treating conditions like Clostridioides difficile infection, but there are concerns about potential short-term and long-term adverse events. While short-term issues may relate to the method of delivery, long-term safety data is limited, and more research is needed to fully understand the risks. ^{2 4 6 7 8}

How is fecal microbiota transplantation different from other treatments for alcoholic hepatitis?

Fecal microbiota transplantation (FMT) is unique because it involves transferring healthy bacteria from a donor's stool to a patient's gut to restore balance in the gut microbiome, which is disrupted in alcoholic hepatitis. Unlike traditional treatments like steroids, which many patients cannot use or do not respond to, FMT directly targets the gut bacteria imbalance, potentially improving liver health and survival rates. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for men and women aged 18-75 with severe alcoholic hepatitis, recently jaundiced due to heavy drinking. They must have specific liver enzyme levels and a MELD score >15 or Maddrey DF score ≥32. Excluded are those with immune deficiencies (not from liver disease), uncontrolled infections, certain other diseases like HIV/HBV/HCV/TB, pregnant/breastfeeding individuals, drug addicts, very high-risk patients as judged by the investigator, recent major abdominal surgery recipients, cancer patients on certain treatments, those at risk of aspiration due to swallowing issues or who have non-alcohol related liver diseases.

Inclusion Criteria

I have severe alcoholic hepatitis with specific blood test results and drinking history.

Exclusion Criteria

Active drug addiction

Pregnant and breastfeeding patients

Serum creatinine >2.5 mg/dl at presentation

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either PRIM-DJ2727 or placebo along with Standard of Care for 4 weeks

4 weeks

Daily visits for the first week, then weekly visits for 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Monthly visits

Treatment Details

Interventions

• Fecal Microbiota Transplantation
• Placebo

Trial Overview The study tests fecal microbiota transplantation (FMT) in capsule form against a placebo in patients with severe alcoholic hepatitis. It's designed to see if FMT can safely improve gut microbiome diversity when taken alongside standard care over four weeks. Participants are randomly assigned to either the FMT group or the placebo group in equal numbers.

Participant Groups

Group I: Intervention Arm Active Control 1 Intervention

Subjects will receive Standard of Care (SOC), based on AASLD/EASL guidelines and one dose of PRIM-DJ2727 (30 grams of stool/dose \~ 3 capsules) every day for a week followed by once weekly for 3 weeks, amounting to total 10 doses. PRIM-DJ2727 (microbiota suspension) is an intestinal microbial suspension prepared form stool obtained from carefully and thoroughly screened healthy human donors. It will be provided by University of Texas School of Public Health.

Group II: Placebo Arm Placebo Group 1 Intervention

Subjects will receive Standard of Care (SOC), based on AASLD/EASL guidelines and one dose of Placebo every day for a week followed by once weekly for 3 weeks, amounting to total 10 doses. Placebo will be identical to the investigational product but will not contain active PRIM-DJ2727.

Fecal Microbiota Transplantation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Fecal Microbiota Transplantation for:

• Graft-versus-host disease (GVHD)
• Clostridioides difficile infection (CDI)

Approved in European Union as Fecal Microbiota Transplantation for:

• Graft-versus-host disease (GVHD)
• Clostridioides difficile infection (CDI)
• Other gastrointestinal disorders

Approved in Canada as Fecal Microbiota Transplantation for:

• Graft-versus-host disease (GVHD)
• Clostridioides difficile infection (CDI)

Who Is Running the Clinical Trial?

Prasun Kumar Jalal

Lead Sponsor

Trials

1

Recruited

50+

Findings from Research

Fecal microbiota transplantation (FMT) shows promise as a treatment for severe alcoholic hepatitis (SAH), addressing the limitations of current steroid therapies, which only benefit a third of patients and have uncertain long-term effects.

Initial human trials indicate that FMT can improve disease severity and survival rates in SAH patients, suggesting it may become a new standard of care with fewer side effects compared to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in alcohol related liver diseases. Shasthry, SM.[2021]

Fecal microbiota transplantation (FMT) significantly improved short-term survival rates in patients with severe alcoholic hepatitis (SAH) presenting as acute-on-chronic liver failure, with 100% survival at 28 days compared to 60% in the standard care group.

FMT was found to be safe, with no significant increase in major adverse events compared to standard care, and it also led to improvements in clinical severity scores, including resolution of hepatic encephalopathy and ascites.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in alcohol-associated acute-on-chronic liver failure: an open-label clinical trial. Sharma, A., Roy, A., Premkumar, M., et al.[2022]

Faecal microbiota transplantation (FMT) showed promising results in a patient with severe alcoholic hepatitis who did not respond to steroid treatment, leading to improvements in clinical and biochemical markers of liver disease.

This case suggests that FMT could be a safe and effective option for patients with steroid-resistant severe alcoholic hepatitis, potentially serving as a bridge to liver transplantation or for those not suitable for transplant, although further research with larger studies is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Healthy donor faecal transplant for corticosteroid non-responsive severe alcoholic hepatitis. Philips, CA., Phadke, N., Ganesan, K., et al.[2019]

Fecal microbiota transplantation (FMT) in patients with severe alcohol-associated hepatitis (SAH) resulted in significantly lower rates of complications such as ascites, infections, and hepatic encephalopathy compared to standard care, suggesting FMT may be a safer treatment option.

Patients receiving FMT also experienced a lower rate of alcohol relapse and a trend towards higher three-year survival rates (65.7% vs. 38.5% for standard care), indicating potential long-term benefits of FMT in managing SAH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Outcomes of Stool Transplant in Alcohol-associated Hepatitis-Analysis of Clinical Outcomes, Relapse, Gut Microbiota and Comparisons with Standard Care. Philips, CA., Ahamed, R., Rajesh, S., et al.[2023]

In a study of 51 male patients with severe alcoholic hepatitis, those receiving healthy donor fecal transplantation (FMT) had a significantly higher survival rate at 3 months (75%) compared to those treated with corticosteroids (38%), nutritional support (29%), or pentoxifylline (30%).

FMT not only improved survival rates but also led to beneficial changes in the gut microbiome and metabolic pathways related to infections and inflammation, suggesting it could be a promising treatment option for severe alcoholic hepatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corticosteroids, nutrition, pentoxifylline, or fecal microbiota transplantation for severe alcoholic hepatitis. Philips, CA., Phadke, N., Ganesan, K., et al.[2019]

Fecal microbiota transplantation (FMT) has a reported adverse event (AE) rate of 39.3%, primarily involving mild and self-limiting issues like abdominal pain and diarrhea, based on a meta-analysis of 9 high-quality studies involving 756 FMTs.

Serious adverse events (SAE) were relatively rare at 5.3%, with the most common being Clostridium difficile infection, indicating that while FMT is generally safe, monitoring and standardized reporting are essential for understanding its long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of fecal microbiota transplantation: a meta-analysis of high-quality studies. Michailidis, L., Currier, AC., Le, M., et al.[2022]

Fecal microbiota transplantation (FMT) in children has an overall effective rate of 85.75%, with a particularly high efficacy of 91.22% for treating Clostridium difficile infections, indicating that FMT is a promising treatment option.

While the overall adverse event rate associated with FMT is 28.86%, most events are mild to moderate, such as bellyache and diarrhea, and are typically self-limiting, suggesting that FMT is generally safe for use in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The global incidence of adverse events associated with fecal microbiota transplantation in children over the past 20 years: A systematic review and meta-analysis. Wang, JG., Liang, Q., Dou, HH., et al.[2022]

Fecal microbiota transplantation (FMT) is recommended for treating recurrent Clostridium difficile infections and has shown benefits for various gastrointestinal disorders, but safety data is still limited due to the rapid adoption of the technique without extensive long-term studies.

Capsulized FMT therapy offers a promising solution for long-term maintenance and reduces the need for invasive procedures, indicating a shift towards safer and more tolerable methods of delivering FMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current research progress and thinking of fecal microbiota transplantation for the treatment of gastrointestinal disorders]. Li, N., Tian, H.[2020]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in alcohol related liver diseases. [2021]

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

Fecal microbiota transplantation in alcohol-associated acute-on-chronic liver failure: an open-label clinical trial. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Healthy donor faecal transplant for corticosteroid non-responsive severe alcoholic hepatitis. [2019]

4. India pubmed.ncbi.nlm.nih.gov

Long-term Outcomes of Stool Transplant in Alcohol-associated Hepatitis-Analysis of Clinical Outcomes, Relapse, Gut Microbiota and Comparisons with Standard Care. [2023]

5. India pubmed.ncbi.nlm.nih.gov

Corticosteroids, nutrition, pentoxifylline, or fecal microbiota transplantation for severe alcoholic hepatitis. [2019]

6. Greece pubmed.ncbi.nlm.nih.gov

Adverse events of fecal microbiota transplantation: a meta-analysis of high-quality studies. [2022]

7. Australia pubmed.ncbi.nlm.nih.gov

The global incidence of adverse events associated with fecal microbiota transplantation in children over the past 20 years: A systematic review and meta-analysis. [2022]

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

[Current research progress and thinking of fecal microbiota transplantation for the treatment of gastrointestinal disorders]. [2020]