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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how Fecal Microbiota Transplantation (FMT or Stool Transplant) can aid individuals with severe alcoholic hepatitis (liver inflammation due to alcohol use). Researchers aim to determine if capsules made from healthy donors' gut bacteria improve the gut health and overall condition of these patients. Participants will receive either the active treatment or a placebo (a look-alike pill with no active ingredients), alongside standard care. Those who have recently experienced jaundice (yellowing of the skin) and have been drinking heavily for months may be suitable for this study. As a Phase 1, Phase 2 trial, this research focuses on understanding the treatment's effects in people and measuring its effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that fecal microbiota transplantation (FMT) is generally safe for people. In a study by Bajaj et al., FMT was safe and even helped reduce alcohol cravings in patients. Another study demonstrated that FMT improved short-term and medium-term survival rates in patients with liver problems related to alcohol use. Clinical severity scores, which measure the seriousness of the condition, also improved after treatment.

FMT uses stool from healthy donors to enhance gut health. This method has been tested in various conditions, including alcoholic hepatitis, with positive results. While side effects can occur, they are usually mild. These findings suggest that FMT is well-tolerated and might be a promising option for those with severe alcoholic hepatitis. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alcoholic Hepatitis?

Unlike the standard treatments for alcoholic hepatitis, which typically involve medications like corticosteroids to reduce liver inflammation, fecal microbiota transplantation (FMT) offers a unique approach by using healthy bacteria from screened donors to restore balance to the gut microbiome. This method targets the underlying gut-liver axis, which could potentially improve liver function and reduce inflammation more effectively. Researchers are excited about FMT because it represents a novel, natural way to address the disease's root causes, rather than just managing symptoms. Plus, it could lead to a more sustainable improvement in liver health for patients who struggle with this challenging condition.

What evidence suggests that Fecal Microbiota Transplantation might be an effective treatment for severe Alcoholic Hepatitis?

Research shows that fecal microbiota transplantation (FMT), which participants in this trial may receive, might help treat severe alcoholic hepatitis (SAH). In one study, patients who received FMT had a higher chance of survival—75% were alive after three months—compared to those who got standard treatment. Another study found that fewer people in the FMT group returned to drinking alcohol, with only 28.6% relapsing compared to 53.8% in the standard care group. Additionally, animal studies have shown that FMT reduces liver damage, suggesting it helps keep the liver healthy. These findings suggest that FMT could improve outcomes for patients with SAH. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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

Serum creatinine >2.5 mg/dl at presentation

Pregnant and breastfeeding patients

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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) 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]

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]

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) 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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9257856/

Long-term Outcomes of Stool Transplant in Alcohol ...

Alcohol relapse was lower (28.6% versus 53.8%), and the time to relapse was higher in the FMT than in the SoC group (P = 0.04). Three-year survival was higher ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11331245/

Impact of fecal microbiota transplantation in severe ...

study, FMT demonstrated superior survival rates among SAH patients after 3 months of follow‐up post‐treatment, with 75% of FMT group survivorship achieved ...

3.

wjgnet.com

wjgnet.com/1007-9327/full/v31/i28/105089.htm

A promising treatment strategy for chronic liver disease

Core Tip: Fecal microbiota transplantation shows significant potential in treating chronic liver diseases by improving liver inflammation, ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S2210740124001992

Therapeutic effects of fecal microbial transplantation on ...

In this study, we found that FMT significantly reduced liver damage in ALD rats, alleviated bacterial translocation, and maintained the integrity of the ...

5.

ngdc.cncb.ac.cn

ngdc.cncb.ac.cn/openlb/publication/OLB-PM-40359297

A systematic review and meta-analysis on the efficacy of ...

Clinical outcomes and gut microbiota analysis of severe alcohol-associated hepatitis patients undergoing healthy donor fecal transplant or ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/35349076/

Fecal microbiota transplantation in alcohol-associated ...

Conclusion: FMT is safe, improves short-term and medium-term survival, and leads to improvement in clinical severity scores in patients with SAH-ACLF. Clinical ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04014413

Safety and Efficacy of Fecal Microbiota Transplantation

Randomized controlled trial has been conducted in a number of disorders and shown positive results, including alcoholic hepatitis, Crohn's disease (CD), ...