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FMT in Cirrhosis and Hepatic Encephalopathy

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ClinicalTrials.gov Identifier: NCT03796598
Recruitment Status : Recruiting
First Posted : January 8, 2019
Last Update Posted : August 2, 2019
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

Brief Summary:
Patients with end stage of liver disease or cirrhosis can develop confusion due to high ammonia and inflammation. This confusion is brought upon by changes in the bacteria in the bowels and may not respond to current standard of care treatments. Repeated episodes of confusion can make it difficult for patients to function and may result in multiple admissions to the hospital and burden on the family. The investigators have studied using a healthy person's stool to replace the bowel bacteria, called fecal microbial transplant, in small studies with good results. In this trial the investigators propose to perform these procedures using an upper and lower route in Veterans who suffer from this condition and follow them for safety and hospitalizations over 6 months. The investigators will compare this to placebo treatments and hope that this intervention can improve the health and daily functioning of affected patients.

Condition or disease Intervention/treatment Phase
Cirrhosis Hepatic Encephalopathy Drug: Fecal Microbial transplant Capsules Drug: Fecal Microbial Transplant Enema Other: Placebo Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Subjects will be divided into 4 groups via randomization

Group 1: Dual oral and rectal FMT, Group 2: Oral FMT and rectal placebo, Group 3: Oral placebo and rectal FMT and Group 4: Oral and rectal placebo

Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Other
Official Title: Fecal Microbiota Transplant in Veterans With Cirrhosis
Actual Study Start Date : July 29, 2019
Estimated Primary Completion Date : June 1, 2023
Estimated Study Completion Date : December 31, 2023


Arm Intervention/treatment
Placebo Comparator: Placebo
Oral and rectal placebo at visit 2 Oral placebo at day 30
Other: Placebo
Placebo

Active Comparator: Group 3: Oral placebo and rectal FMT
Oral placebo and rectal FMT at visit 2 Oral placebo at day 30
Drug: Fecal Microbial Transplant Enema
FMT enema

Other: Placebo
Placebo

Active Comparator: Group 2: Oral FMT and rectal placebo
Oral FMT and rectal placebo at visit 2 Oral FMT at day 30
Drug: Fecal Microbial transplant Capsules
Oral capsules of FMT

Experimental: Group 1: Dual Oral and rectal FMT
Dual Oral and rectal FMT at visit 2 Oral FMT at day 30
Drug: Fecal Microbial transplant Capsules
Oral capsules of FMT

Drug: Fecal Microbial Transplant Enema
FMT enema




Primary Outcome Measures :
  1. Serious adverse events related to FMT [ Time Frame: 6 months ]
    Number of serious adverse events between groups related to FMT


Secondary Outcome Measures :
  1. Adverse events related to FMT [ Time Frame: 6 months ]
    Number of adverse events that do not fit the criteria of serious adverse events between groups related to FMT

  2. Change in microbial diversity in stool [ Time Frame: 6 months ]
    Shannon diversity index compared to baseline and engraftment related to the donor at baseline, within 30 days and then monthly till 6 months

  3. Change in Intestinal Permeability defined by lactulose mannitol test [ Time Frame: 30 days ]
    Lactulose mannitol ratio in urine will be used to analyze intestinal permeability at baseline and at day 30. Changes in intestinal permeability over this time period will be analyzed between groups

  4. Sickness Impact Profile change [ Time Frame: 30 days and 6 months ]
    Quality of life assessment change defined by Sickness Impact Profile total score at 30 days and 6 months between groups

  5. EncephalApp performance change [ Time Frame: 30 days, 60 days and 6 months ]
    Cognitive assessment change using the OffTime+OnTime in seconds between groups at 30 days, 60 days and 6 months

  6. Psychometric hepatic encephalopathy score (PHES) change [ Time Frame: 30 days, 60 days and 6 months ]
    Cognitive assessment change using the total PHES score between groups at 30 days, 60 days and 6 months

  7. Change in microbial diversity in saliva [ Time Frame: 6 months ]
    Shannon diversity index compared to baseline at 30 days and then monthly till 6 months

  8. Change in microbial diversity in blood [ Time Frame: 6 months ]
    Shannon diversity index compared to baseline at 30 days and then monthly till 6 months



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Cirrhosis diagnosed by either of the following in a patient with chronic liver disease

    • Liver Biopsy
    • Radiologic evidence of varices, cirrhosis or portal hypertension
    • Laboratory evidence of platelet count <100,000 or AST/ALT ratio>1
    • Endoscopic evidence of varices or portal gastropathy
    • Fibroscan values suggestive of cirrhosis
  • On treatment for hepatic encephalopathy (patient can be on lactulose and rifaximin)
  • Able to give written, informed consent (demonstrated by mini-mental status exam>25 at the time of consenting)
  • Women of child bearing potential must agree to use effective contraception for the duration of the study and for 10 days prior and 30 days after the study
  • Negative pregnancy test in women of childbearing age

Exclusion Criteria:

  • MELD score >22
  • WBC count <1000 cells/mm3
  • Platelet count<50,000/mm3
  • TIPS in place for less than a month
  • Currently on antibiotics apart from rifaximin
  • Infection at the time of the FMT (diagnosed by blood culture positivity, urinalysis, paracentesis as needed)
  • Hospitalization for any non-elective cause within the last 1 month
  • Patients who are aged >75 years
  • Patients who are pregnant or nursing (will be checked using a urine pregnancy test)
  • Patients who are incarcerated
  • Patients who are incapable of giving their own informed consent
  • Patients who are immuno-compromised due to the following reasons:

    • HIV infection (any CD4 count)
    • Inherited/primary immune disorders
    • Current or recent (<3 mos) treatment with anti-neoplastic agent
    • Current or recent (<3 mos) 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
  • Patients on renal replacement therapy
  • Patients with untreated, in-situ colorectal cancer
  • Patients with a history of chronic intrinsic GI diseases such as inflammatory bowel disease

    • ulcerative colitis, Crohn's disease or microscopic colitis

      • eosinophilic gastroenteritis or celiac disease
  • Major gastro-intestinal or intra-abdominal surgery in the last three months

Other Exclusion Criteria:

  • Enema-related

    • Platelet count<50,000
    • Grade IV hemorrhoids
  • Safety-related:

    • Dysphagia
    • History of aspiration, gastroparesis, intestinal obstruction
    • Ongoing antibiotic use (except for Rifaximin)
    • Severe anaphylactic food allergy
    • Allergy to ingredients Generally Recognized As Safe in the FMT capsules (glycerol, sodium chloride, hypromellose, gellan gum, titanium dioxide, theobroma oil)
    • Adverse event attributable to prior FMT
    • ASA Class IV or V
    • Pregnant or nursing patients
    • Acute illness or fever within 48 hours of the day of planned FMT
    • Immunocompromised due to medical conditions
    • Probiotics use within the last 48 hours of the day of planned FMT
    • Any condition that the physician investigators deem unsafe, including other conditions or medications that the investigator determines puts the participant at greater risk from FMT

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03796598


Contacts
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Contact: Jasmohan S Bajaj, MD MS (804) 675-5802 Jasmohan.Bajaj@va.gov
Contact: Edith A Gavis, RN (804) 675-5584 edith.gavis@va.gov

Locations
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United States, Virginia
Hunter Holmes McGuire VA Medical Center, Richmond, VA Recruiting
Richmond, Virginia, United States, 23249
Contact: Edith A Gavis, RN    804-675-5584    edith.gavis@va.gov   
Contact: Jasmohan S Bajaj, MD MS    (804) 675-5802    Jasmohan.Bajaj@va.gov   
Principal Investigator: Jasmohan S. Bajaj, MD MS         
Sponsors and Collaborators
VA Office of Research and Development
Investigators
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Principal Investigator: Jasmohan S. Bajaj, MD MS Hunter Holmes McGuire VA Medical Center, Richmond, VA

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Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT03796598     History of Changes
Other Study ID Numbers: GAST-001-18S
CX001076 ( Other Grant/Funding Number: Office of Research and Development, VA )
First Posted: January 8, 2019    Key Record Dates
Last Update Posted: August 2, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by VA Office of Research and Development:
fecal microbial transplant
cirrhosis
hepatic encephalopathy

Additional relevant MeSH terms:
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Liver Cirrhosis
Fibrosis
Brain Diseases
Hepatic Encephalopathy
Pathologic Processes
Liver Diseases
Digestive System Diseases
Central Nervous System Diseases
Nervous System Diseases
Liver Failure
Hepatic Insufficiency
Brain Diseases, Metabolic
Metabolic Diseases