CirrhosisPhase 1NCT03416751
Fecal Microbial Transplant for Alcohol Misuse in Cirrhosis
A Phase 1 study testing Fecal Microbial Transplant in people with Cirrhosis and Alcohol Abuse, run by Hunter Holmes Mcguire Veteran Affairs Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 75 years
- Conditions the study is for
- Cirrhosis, Alcohol Abuse
- What is being tested?
- Fecal Microbial Transplant
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2018to 10 Apr 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Cirrhosis diagnosed by any 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 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
- 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
Who cannot join
- 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
- Patients who are immuno-compromised due to the following reasons:
- HIV infection (any CD4 count)
- Inherited/primary immune disorders
- Current or recent (<3 months) treatment with anti-neoplastic agent
- 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.
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Hunter Holmes McGuire VA Medical Center
Richmond, Virginia, 23249
About this study
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.
Read the 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.
- Conditions
- Cirrhosis, Alcohol Abuse
- Being tested
- Fecal Microbial Transplant, Placebo
- Medical subject headings
- Fibrosis, Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fecal Microbial TransplantBiological
Fecal transplant from a donor in the OpenBiome Registry
PlaceboOther
Placebo enemas
| Study group | Role | What they receive |
|---|---|---|
| Fecal Microbial transplantation | Experimental | Patients will get one-dose of 90ml of FMT enema on day 1 that has been received from OpenBiome using a rational donor Receives: Biological: Fecal Microbial Transplant |
| Placebo | Placebo comparator | Patients will get one-dose of 90ml of saline enema on day 1 Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of participants with a related serious adverse event
Related SAE to FMT
Measured: 15 days
Proportion of participants with newly acquired transmissible infectious diseases
Related transmissible infectious disease to FMT
Measured: 15 days
Proportion of participants with a related adverse event
Related adverse event that does not meet the criteria for a serious adverse event
Measured: 15 days
Secondary outcomes (10)
Proportion of participants with a related serious adverse event
Related SAE to FMT
Measured: 30 days and 6 months
Proportion of participants with a related adverse event
Related adverse event that does not meet the criteria for a serious adverse event
Measured: 30 days and 6 months
Proportion of participants with newly acquired transmissible infectious diseases
Related transmissible infectious disease to FMT
Measured: 30 days and 6 months
Composition of microbial change
UNIFRAC and LEFSe pre vs post FMT on stool microbiota compared to baseline and to placebo
Measured: day 15 post-intervention
AUDIT questionnaire
defining changes in alcohol abuse severity compared to baseline and to placebo
Measured: day 15 post-intervention
Alcohol craving questionnaire
defining changes in the cravings for alcohol compared to baseline and to placebo
Measured: day 15 post-intervention
Systemic inflammation changes
Inflammatory cytokines (IL-6, TNF, IL-1b) compared to baseline and to placebo
Measured: day 15 post-intervention
Cognition change using PHES
Psychometric hepatic encephalopathy score compared to baseline and to placebo
Measured: day 15 post-intervention
Cognition change using EncephalApp stroop
EncephalApp stroop compared to baseline and to placebo
Measured: day 15, 30 and 6 months post-intervention
Quality of Life using Sickness Impact Profile
Sickness Impact Profile compared to baseline and to placebo
Measured: day 15 post-intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2018
- Study start1 Feb 2018
- Primary completion10 Apr 2020
- Study completion10 Apr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CirrhosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hunter Holmes Mcguire Veteran Affairs Medical Center
- Sponsor type
- US federal agency
- Collaborators
- OpenBiome
- Responsible party
- Sponsor
- Investigators
- Jasmohan S Bajaj, MD, Principal investigator, Hunter Holmes McGuire VA Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03416751
- Sponsor's protocol ID
- BAJAJ0021A
- Status last verified
- Jul 2020
- First submitted
- 11 Jan 2018
- Last updated
- 28 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fecal Microbial Transplant for Alcohol Misuse in Cirrhosis
- ClinicalTrials.gov ID
- NCT03416751
- Acronym / sponsor ID
- BAJAJ0021A
- Conditions
- Cirrhosis, Alcohol Abuse
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Hunter Holmes Mcguire Veteran Affairs Medical CenterUS federal agency
- Collaborators
- OpenBiome
- Study start
- 1 Feb 2018 (actual)
- Primary completion
- 10 Apr 2020 (actual)
- Study completion
- 10 Apr 2020 (actual)
- First posted
- 31 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fecal Microbial transplantation | Experimental | Biological: Fecal Microbial TransplantPatients will get one-dose of 90ml of FMT enema on day 1 that has been received from OpenBiome using a rational donor |
| Placebo | Placebo comparator | Other: PlaceboPatients will get one-dose of 90ml of saline enema on day 1 |
Who may qualify
- Ages
- 21 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Cirrhosis diagnosed by any 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
Key exclusion criteria (7 listed)
- 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
- Patients who are immuno-compromised due to the following reasons:
- HIV infection (any CD4 count)
- Inherited/primary immune disorders
- Current or recent (<3 months) treatment with anti-neoplastic agent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fecal Microbial TransplantFecal transplant from a donor in the OpenBiome Registry | Biological | Fecal Microbial transplantation |
| PlaceboPlacebo enemas | Other | Placebo |
Primary outcome
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
10 secondary outcomes
Proportion of participants with a related serious adverse event
Time frame: 30 days and 6 months
Proportion of participants with a related adverse event
Time frame: 30 days and 6 months
Proportion of participants with newly acquired transmissible infectious diseases
Time frame: 30 days and 6 months
Composition of microbial change
Time frame: day 15 post-intervention
AUDIT questionnaire
Time frame: day 15 post-intervention
Alcohol craving questionnaire
Time frame: day 15 post-intervention
Systemic inflammation changes
Time frame: day 15 post-intervention
Cognition change using PHES
Time frame: day 15 post-intervention
Cognition change using EncephalApp stroop
Time frame: day 15, 30 and 6 months post-intervention
Quality of Life using Sickness Impact Profile
Time frame: day 15 post-intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2020.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jasmohan S Bajaj, MD principal investigator
Hunter Holmes McGuire VA Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fecal Microbial Transplant in people with Cirrhosis and Alcohol Abuse, run by Hunter Holmes Mcguire Veteran Affairs Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of participants with a related serious adverse event (time frame: 15 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2020.