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Fecal Microbial Transplant for Alcohol Misuse in Cirrhosis

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ClinicalTrials.gov Identifier: NCT03416751
Recruitment Status : Recruiting
First Posted : January 31, 2018
Last Update Posted : August 26, 2019
Sponsor:
Collaborator:
OpenBiome
Information provided by (Responsible Party):
Hunter Holmes Mcguire Veteran Affairs Medical Center

Tracking Information
First Submitted Date  ICMJE January 11, 2018
First Posted Date  ICMJE January 31, 2018
Last Update Posted Date August 26, 2019
Actual Study Start Date  ICMJE January 5, 2018
Estimated Primary Completion Date November 5, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 24, 2018)
  • Proportion of participants with a related serious adverse event [ Time Frame: 15 days ]
    Related SAE to FMT
  • Proportion of participants with newly acquired transmissible infectious diseases [ Time Frame: 15 days ]
    Related transmissible infectious disease to FMT
  • Proportion of participants with a related adverse event [ Time Frame: 15 days ]
    Related adverse event that does not meet the criteria for a serious adverse event
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03416751 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 24, 2018)
  • Proportion of participants with a related serious adverse event [ Time Frame: 30 days and 6 months ]
    Related SAE to FMT
  • Proportion of participants with a related adverse event [ Time Frame: 30 days and 6 months ]
    Related adverse event that does not meet the criteria for a serious adverse event
  • Proportion of participants with newly acquired transmissible infectious diseases [ Time Frame: 30 days and 6 months ]
    Related transmissible infectious disease to FMT
  • Composition of microbial change [ Time Frame: day 15, 30 and 6 months post-intervention ]
    UNIFRAC and LEFSe pre vs post FMT on stool microbiota compared to baseline and to placebo
  • AUDIT questionnaire [ Time Frame: day 15, 30 and 6 months post-intervention ]
    defining changes in alcohol abuse severity compared to baseline and to placebo
  • Alcohol craving questionnaire [ Time Frame: day 15, 30 and 6 months post-intervention ]
    defining changes in the cravings for alcohol compared to baseline and to placebo
  • Systemic inflammation changes [ Time Frame: day 15, 30 and 6 months post-intervention ]
    Inflammatory cytokines (IL-6, TNF, IL-1b) compared to baseline and to placebo
  • Cognition change using PHES [ Time Frame: day 15, 30 and 6 months post-intervention ]
    Psychometric hepatic encephalopathy score compared to baseline and to placebo
  • Cognition change using EncephalApp stroop [ Time Frame: day 15, 30 and 6 months post-intervention ]
    EncephalApp stroop compared to baseline and to placebo
  • Quality of Life using Sickness Impact Profile [ Time Frame: day 15, 30 and 6 months post-intervention ]
    Sickness Impact Profile compared to baseline and to placebo
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Fecal Microbial Transplant for Alcohol Misuse in Cirrhosis
Official Title  ICMJE Fecal Microbial Transplant for Alcohol Misuse in Cirrhosis
Brief Summary

There is an epidemic of alcohol use disorder in the US. Alcoholism is an epidemic that spans all ages and socio-economic strata, which has a major impact on healthcare expenditure. Alcohol-associated liver disease can take the form of mild fatty liver, chronic liver disease including cirrhosis and a very acute active form known as alcoholic hepatitis. However, most patients with alcohol abuse issues with cirrhosis do not develop alcoholic hepatitis and are not willing to quit drinking. These patients are neither liver transplant candidates due to their drinking nor have any recourse to therapies directed towards the liver as is the case with alcoholic hepatitis. This is very large proportion of cirrhotic patients who do not have many therapeutic options.

Prior studies have demonstrated that these patients have an altered gut-liver axis which is exacerbated by dysbiosis and a higher production of potentially toxic secondary bile acids. These secondary bile acids in turn have the potential to worsen the already impaired gut barrier in these patients, creating a vicious cycle of inflammation and further liver injury that is led by the altered microbial composition. A gut-based strategy that has the capability of "resetting" this dysbiosis could help in the amelioration of this inflammatory load and improve the prognosis of these patients.

Detailed Description

Randomized, single-blind, placebo-controlled safety, tolerability study with exploratory endpoints and pathophysiological evaluation of the FMT

Two groups of outpatients with cirrhosis will be randomized using random sequence generator into no-treatment and FMT groups.

Once patients are randomized 1:1 into group 1 (FMT) and group 2 (Placebo), both will be followed over 31 days and will include a 6 month visit to collect samples, perform questionnaires and to assess SAEs.

There is an epidemic of alcohol use disorder in the US. Alcoholism is an epidemic that spans all ages and socio-economic strata, which has a major impact on healthcare expenditure. Alcohol-associated liver disease can take the form of mild fatty liver, chronic liver disease including cirrhosis and a very acute active form known as alcoholic hepatitis. However, most patients with alcohol abuse issues with cirrhosis do not develop alcoholic hepatitis and are not willing to quit drinking. These patients are neither liver transplant candidates due to their drinking nor have any recourse to therapies directed towards the liver as is the case with alcoholic hepatitis. This is very large proportion of cirrhotic patients who do not have many therapeutic options.

Prior studies have demonstrated that these patients have an altered gut-liver axis which is exacerbated by dysbiosis and a higher production of potentially toxic secondary bile acids. These secondary bile acids in turn have the potential to worsen the already impaired gut barrier in these patients, creating a vicious cycle of inflammation and further liver injury that is led by the altered microbial composition. The investigators believe that a gut-based strategy that has the capability of "resetting" this dysbiosis can help in the amelioration of this inflammatory load and improve the prognosis of these patients.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Cirrhosis
  • Alcohol Abuse
Intervention  ICMJE
  • Biological: Fecal Microbial Transplant
    Fecal transplant from a donor in the OpenBiome Registry
  • Other: Placebo
    Placebo enemas
Study Arms  ICMJE
  • Experimental: Fecal Microbial transplantation
    Patients will get one-dose of 90ml of FMT enema on day 1 that has been received from OpenBiome using a rational donor
    Intervention: Biological: Fecal Microbial Transplant
  • Placebo Comparator: Placebo
    Patients will get one-dose of 90ml of saline enema on day 1
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 24, 2018)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 5, 2019
Estimated Primary Completion Date November 5, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

A. Cirrhosis diagnosed by any of the following in a patient with chronic liver disease:

  1. Liver Biopsy
  2. Radiologic evidence of varices, cirrhosis or portal hypertension
  3. Laboratory evidence of platelet count <100,000 or AST/ALT ratio>1
  4. Endoscopic evidence of varices or portal gastropathy
  5. Fibroscan B. Age between 21 and 75 C. Able to give written, informed consent (demonstrated by mini-mental status exam>25 at the time of consenting) D. Subject must have alcohol as a cause of cirrhosis

i. Continued sustained drinking pattern with AUDIT score ≥8 in the last month and fulfilling DSM-V criteria for alcohol misuse ii. Unable or unwilling to get mental health attention to quit alcohol (at least 3-months period of referrals to Substance abuse programs or other alcohol treatment approaches) iii. Adult companion who can accompany patient and provide insight into alcohol drinking patterns

Exclusion Criteria:

A. MELD score >17 B. Child Class C C. WBC count <1000 cells/mm3 D. Platelet count<50,000/mm3 E. TIPS in place for less than a month F. HE episode within a month prior to the study G. Currently on absorbable antibiotics H. Infection at the time of the FMT (diagnosed by blood culture positivity, urinalysis, paracentesis as needed) I. Patients who are aged >75 years J. Patients who are pregnant or nursing (will be checked using a urine pregnancy test) K. Patients who are incarcerated L. Patients who are incapable of giving their own informed consent

M. Patients who are immuno-compromised due to the following reasons:

  1. HIV infection (any CD4 count)
  2. Inherited/primary immune disorders
  3. Current or recent (<3 months) treatment with anti-neoplastic agent
  4. Current or recent (<3 months) treatment with any immunosuppressant medications [including but not limited to monoclonal antibodies to B and T cells, anti-TNF agents, glucocorticoids, antimetabolites (azathioprine, 6-mercaptopurine), calcineurin inhibitors (tacrolimus, cyclosporine), mycophenolate mofetil]. Subjects who are otherwise immunocompetent and have discontinued any immunosuppressant medications 3 or more months prior to enrollment may be eligible to enroll.

N. Patients with a history of severe (anaphylactic) food allergy O. Patients who have previously undergone FMT P. Patients on renal replacement therapy Q. Patients who are unwilling or unable to hold the enemas R. Patients with untreated, in-situ colorectal cancer S. Patients with a history of chronic intrinsic GI diseases such as inflammatory bowel disease (ulcerative colitis, Crohn's disease or microscopic colitis), eosinophilic gastroenteritis, celiac disease or irritable bowel syndrome T. Major gastro-intestinal or intra-abdominal surgery in the last three months U. Unable to comply with protocol requirements V. Patients who are American Society of Anesthesiologists (ASA) Physical Status classification IV and V W. Patients with acute illness or fever on the day of planned FMT will be excluded with the option of including that subject at a future date X. Any conditions for which, in opinion of MD, the treatment may pose a health risk Y. Grade 2-4 or complicated hemorrhoids

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jasmohan S Bajaj, MD 804 675 5802 jsbajaj@vcu.edu
Contact: Jill Meador, RN 804 675 6407 jill.meador@va.gov
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03416751
Other Study ID Numbers  ICMJE BAJAJ0021A
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Hunter Holmes Mcguire Veteran Affairs Medical Center
Study Sponsor  ICMJE Hunter Holmes Mcguire Veteran Affairs Medical Center
Collaborators  ICMJE OpenBiome
Investigators  ICMJE
Principal Investigator: Jasmohan S Bajaj, MD Hunter Holmes McGuire VA Medical Center
PRS Account Hunter Holmes Mcguire Veteran Affairs Medical Center
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP