Bacteria Capsules for Alcoholic Liver Disease

(IMPACT Trial)

Recruiting at 1 trial location

Overseen By Amy Bartels, BSN, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Virginia Commonwealth University

Must not be taking: Absorbable antibiotics

Disqualifiers: Illicit drugs, Mood disorders, Dialysis, others

Compensation: Varies

Number of Visits: 8

Duration: 3 months

80 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to test the safety, tolerability, and effectiveness of the capsules that contain bacteria from healthy individuals when used to treat alcohol craving and drinking.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, ongoing use of absorbable antibiotics is not allowed, so you may need to stop those if you are taking them.

What data supports the effectiveness of this treatment for alcoholic liver disease?

Research shows that fecal microbiota transplantation (FMT) is effective for treating Clostridium difficile infections and is being explored for other conditions like inflammatory bowel disease. Encapsulated FMT, similar to the bacteria capsules in this trial, has shown promise in these areas, suggesting potential benefits for alcoholic liver disease as well. ^{1 2 3 4 5}

Is the use of bacteria capsules (FMT/IMT) generally safe for humans?

Fecal microbiota transplantation (FMT), which involves using bacteria capsules, is considered safe for treating recurrent Clostridium difficile infections and is being studied for other conditions. While more research is needed, studies have shown it to be a promising and generally safe approach for various conditions, including inflammatory bowel disease. ^{1 6 7 8 9}

How is the treatment with Intestinal Microbiota Transplant (IMT) Capsules different from other treatments for alcoholic liver disease?

The Intestinal Microbiota Transplant (IMT) Capsules are unique because they aim to restore a healthy balance of gut bacteria, which is disrupted in alcoholic liver disease, by using bacteria from healthy donors. This approach is different from traditional treatments like steroids, which many patients cannot use or do not respond to, and it offers a potential new way to improve liver health and survival rates. ^{10 11 12 13 14}

Research Team

Jasmohan S Bajaj, MD

Principal Investigator

Virginia Commonwealth University

Eligibility Criteria

This trial is for adults over 18 with advanced liver disease due to alcohol use, who continue to drink despite previous attempts at treatment. They must be able to consent and not have withdrawal symptoms, significant drug use, uncontrolled mood disorders, certain allergies, a high MELD score (>17), or other severe health issues.

Inclusion Criteria

Able to give written, informed consent

My advanced liver disease is due to alcohol use.

Continued sustained drinking

Exclusion Criteria

My liver disease diagnosis is unclear.

I am currently receiving dialysis.

Severe anaphylactic food allergy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either IMT capsules or placebo capsules, with capsules given twice on enrollment and after one month

3 months

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including tracking of hospitalizations and serious adverse events

4 months

Treatment Details

Interventions

• Intestinal Microbiota Transplant (IMT) Capsules
• Placebo Capsules

Trial Overview The study tests if capsules containing bacteria from healthy donors can reduce alcohol craving and consumption in patients with alcoholic liver disease. Participants will either receive the actual microbiota capsules or placebo capsules without active ingredients.

Participant Groups

Group I: Intestinal Microbiota Transplant capsules Experimental Treatment 1 Intervention

Capsules will be provided twice during the trial

Group II: Placebo capsules Placebo Group 1 Intervention

Capsules will be provided twice during the trial

Intestinal Microbiota Transplant (IMT) Capsules is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as Fecal Microbiota Transplantation for:

• Recurrent Clostridioides difficile infection (CDI)

Approved in European Union as Faecal Microbiota Transplantation for:

• Recurrent Clostridioides difficile infection (CDI)
• Severe to fulminant CDI
• Inflammatory bowel diseases including pouchitis
• Irritable bowel syndrome

Approved in United Kingdom as Fecal Microbiota Transplantation for:

• Recurrent Clostridioides difficile infection (CDI)
• Refractory CDI

Who Is Running the Clinical Trial?

Virginia Commonwealth University

Lead Sponsor

Trials

732

Recruited

22,900,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Findings from Research

The study demonstrated that daily oral administration of frozen encapsulated fecal microbiota transplantation (cFMT) is safe and well-tolerated in patients with mild to moderate ulcerative colitis (UC), with no treatment-related adverse events reported.

Two out of six subjects receiving cFMT achieved clinical remission, suggesting that cFMT may help maintain beneficial changes in gut microbiota and improve clinical outcomes, although further research is needed to confirm these findings and address home storage issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daily, oral FMT for long-term maintenance therapy in ulcerative colitis: results of a single-center, prospective, randomized pilot study. Crothers, JW., Chu, ND., Nguyen, LTT., et al.[2022]

Faecal microbiota transplantation (FMT) has a high cure rate of 95.6% for Clostridium difficile infections (CDI), indicating its efficacy as a treatment for this condition.

The study revealed significant variability in donor screening and characteristics, with less than 50% of studies screening for transmittable pathogens, highlighting the need for standardized protocols in FMT procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review with meta-analysis: review of donor features, procedures and outcomes in 168 clinical studies of faecal microbiota transplantation. Lai, CY., Sung, J., Cheng, F., et al.[2020]

Faecal microbiota transplantation (FMT) shows promising short to medium-term efficacy for treating ulcerative colitis (UC), supported by numerous case series and results from four randomized controlled trials since 1989.

Despite its potential, there are ongoing controversies regarding the methodology, underlying mechanisms, and safety of FMT, indicating that further research is needed to clarify these aspects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Faecal transplantation for IBD management-pitfalls and promises. Quraishi, MN., Critchlow, T., Bhala, N., et al.[2022]

Encapsulated faecal microbiota transplantation (FMT) is a highly effective and safe treatment for recurrent Clostridioides difficile infection (rCDI), achieving cure rates of 85% after a single course and 93% after multiple courses, based on a systematic review of 35 studies involving 960 patients.

The efficacy of encapsulated FMT for rCDI remains consistent despite variations in treatment protocols, donor screening, and capsule preparation, indicating that this method is as effective as traditional FMT delivery routes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review with meta-analysis: encapsulated faecal microbiota transplantation - evidence for clinical efficacy. Cold, F., Baunwall, SMD., Dahlerup, JF., et al.[2022]

Faecal microbiota transplantation (FMT) has proven to be highly effective in treating Clostridium difficile infection (CDI), with over 500 cases showing it is generally well tolerated and has minimal side effects.

Research is expanding into the use of FMT for other gastrointestinal and extra-intestinal conditions, with promising preliminary findings, particularly in inflammatory bowel disease, and new products like frozen gastrointestinal microbiota extracts are being developed for easier delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic faecal microbiota transplantation: current status and future developments. Borody, TJ., Brandt, LJ., Paramsothy, S.[2021]

Fecal Microbiota Transplantation (FMT) is a promising therapeutic approach that involves transferring healthy donor stool to restore gut microbiota, which can help defend against infections and reduce the risk of invasive infections.

FMT has shown significant success in treating recurrent Clostridioides difficile infections, and ongoing research is exploring its potential for treating other infectious diseases by leveraging the relationship between gut microbiota and infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential utility of fecal (or intestinal) microbiota transplantation in controlling infectious diseases. Ghani, R., Mullish, BH., Roberts, LA., et al.[2022]

Fecal microbiota transplantation (FMT) is a safe and effective treatment for recurrent Clostridium difficile infections, and research is expanding to explore its potential for treating other conditions related to chronic inflammation and autoimmunity.

Current studies on FMT for conditions like ulcerative colitis and metabolic syndrome show promise, but many lack rigorous methodology, highlighting the need for more standardized and well-designed trials to validate these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Fecal microbiota transplantation : current status and prospects]. Gilbert, B., Schrenzel, J.[2019]

Fecal microbiota transplantation (FMT) is emerging as a promising strategy to restore normal gut microbiota in patients with inflammatory bowel disease (IBD), potentially complementing existing immune modulation treatments.

While FMT shows potential efficacy, there are still uncertainties regarding the best predictors for treatment response, optimal administration methods, and the ideal characteristics of the transplanted microbiota, highlighting the need for further research on long-term outcomes and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of fecal microbiota transplantation in inflammatory bowel disease. D'Odorico, I., Di Bella, S., Monticelli, J., et al.[2018]

Fecal microbiota transplantation (FMT) is being explored as a treatment for various health conditions, highlighting its potential therapeutic benefits.

The FDA is focused on ensuring the safety of FMT products through rigorous donor screening and manufacturing processes, which is crucial for conducting safe clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulatory Considerations for Fecal Microbiota Transplantation Products. Carlson, PE.[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]

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) 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) 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) significantly reduces liver fat accumulation in patients with non-alcoholic fatty liver disease (NAFLD) by improving gut microbiota balance, as shown in a randomized controlled trial.

The study found that FMT was more effective in lean NAFLD patients compared to obese patients, highlighting the varying impacts of FMT based on body composition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Fecal Microbiota Transplantation on Non-Alcoholic Fatty Liver Disease: A Randomized Clinical Trial. Xue, L., Deng, Z., Luo, W., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Daily, oral FMT for long-term maintenance therapy in ulcerative colitis: results of a single-center, prospective, randomized pilot study. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Systematic review with meta-analysis: review of donor features, procedures and outcomes in 168 clinical studies of faecal microbiota transplantation. [2020]

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

Faecal transplantation for IBD management-pitfalls and promises. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Systematic review with meta-analysis: encapsulated faecal microbiota transplantation - evidence for clinical efficacy. [2022]

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

Therapeutic faecal microbiota transplantation: current status and future developments. [2021]

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

The potential utility of fecal (or intestinal) microbiota transplantation in controlling infectious diseases. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

[Fecal microbiota transplantation : current status and prospects]. [2019]

8. Australia pubmed.ncbi.nlm.nih.gov

Role of fecal microbiota transplantation in inflammatory bowel disease. [2018]

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

Regulatory Considerations for Fecal Microbiota Transplantation Products. [2020]

10. India pubmed.ncbi.nlm.nih.gov

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

11. England pubmed.ncbi.nlm.nih.gov

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

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

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

13. 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]

14. Switzerland pubmed.ncbi.nlm.nih.gov

Effect of Fecal Microbiota Transplantation on Non-Alcoholic Fatty Liver Disease: A Randomized Clinical Trial. [2022]