Hepatic EncephalopathyPhase 1NCT02636647
Fecal Transplant in Recurrent Hepatic Encephalopathy
A Phase 1 study testing Fecal transplant in people with Hepatic Encephalopathy and Cirrhosis, run by Jasmohan Bajaj at 1 site in United States.
Trial summary
Randomized, open-label 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. Read more about this study
- Who is it for?
- Ages 21 to 75 years
- Conditions the study is for
- Hepatic Encephalopathy, Cirrhosis
- What is being tested?
- Fecal transplant
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2015to Aug 2016
- 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 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
- At least two episodes of hepatic encephalopathy, one within the last year but not within the last month (patient can be on lactulose and rifaximin)
- Age between 21 and 75
- Able to give written, informed consent (demonstrated by mini-mental status exam>25 at the time of consenting)
Who cannot join
- MELD score >17
- WBC count <1000 cells/mm3
- Platelet count<50,000/mm3
- On the liver transplant list
- TIPS in place
- No HE episode within a month prior to the study
Show all 32Show fewer
- Patients allergic to ciprofloxacin, penicillins or metronidazole
- Currently on absorbable antibiotics
- 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 3 months
- 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 with a history of severe (anaphylactic) food allergy
- Patients who have previously undergone FMT
- Patients on renal replacement therapy
- Patients who are unwilling or unable to hold the enemas
- 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, celiac disease or irritable bowel syndrome
- Major gastro-intestinal or intra-abdominal surgery in the last three months
- Unable to comply with protocol requirements
- Patients who are American Society of Anesthesiologists (ASA) Physical Status classification IV and V
- 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
- Any conditions for which, in opinion of MD, the treatment may pose a health risk
- C. difficile in the stool at baseline (qPCR)
- 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
Official title: Safety and Tolerability of Fecal Microbiota Transplantation in Cirrhosis and Hepatic Encephalopathy
Randomized, open-label 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.
Read the detailed description
Group 1 (FMT group) will undergo the following procedures
Pre-FMT preparation:
We will obtain written informed consent per the IRB guidelines. After the patients are consented and are eligible, we will perform a detailed medical history and physical exam at day 0. We will also perform cognitive testing. As in prior studies, we will prescribe patients an antibiotic regimen. Drawing from ecological principles of microbial niche environments and data from recurrent Clostridium difficile infection, pre-treatment antibiotics are likely to increase the probability of disrupting the hosts intrinsic microbiota and creating an opportunity for a 'healthy' microbiota from the FMT to engraft.
After antibiotics and on the day of FMT:
At day 5, we will re-evaluate patients with a directed interval history and focused physical exam as needed. After ensuring that they are still candidates according to the inclusion/exclusion criteria, we will collect stool, urine and blood again for pre-FMT evaluation and urine for pregnancy tests from eligible women. Cognitive testing will be performed again.
Preparation and handling of stool for FMT infusion
Standard protocol for handling bio-hazardous material will be employed in order to avoid contamination and risk to healthcare handlers. Sterile microbiological technique will be employed during material transfer peri-procedure.
At that point we will provide the fecal material using universal precautions to a standard retention enema bag. The procedure will be completed by a trained Registered Nurse, Nurse practitioner, or physician in an outpatient clinic, endoscopy recovery area, or standard endoscopy unit.
The following will be recorded in all FMTs
- Dose
- Unit ID/Lot# of each treatment
- Expiration Date
- Storage Condition
- FMT retention time (in minutes)
Number of FMT: One administration Duration of Follow-up after FMT: 5 months
Follow-up after FMT:
We will see the patient in clinic the day following FMT (day 6 or FMT+1), day 12 (FMT+7), day 20 (FMT+15), and day 35 (FMT+30), at which point a detailed history regarding abdominal symptoms, evaluation of infectious complications, hospitalizations or complications of cirrhosis.
Visits on day 6, day 12 and day 35 will be purely safety associated while, on the day 20 visit, we will repeat the pathophysiological studies.
In order to ensure that we have enough samples, in case patients are not able to return at day 20, we will also collect all samples at day 12, but will only analyze them in case the day 20 visit does not occur.
These visits, apart from the visit after FMT, will be ±2 days for patient convenience.
At 5 months post-FMT, subjects will be followed up with a phone call to evaluate potential SAEs, new onset of transmitted infections, new onset or significant worsening of chronic medical conditions or suspected unexpected serious adverse reactions that have occurred in between 35 days and 5 months for reporting purposes.
Samples collected at baseline (before FMT), after antibiotics and at day 15 will be:
- Stool
- Blood
- Urine
Group 2: No treatment arm The group 2 will undergo all sample collections, follow-up and cognitive testing as in group 1 but without the 5-day antibiotic therapy or the FMT. In addition, we will also not perform the sample collection that is done after 5 days of antibiotics in this group since no reasonable change in microbiota are expected over 5 days without antibiotics. The follow-up of this group will be same as that of the FMT group.
- Conditions
- Hepatic Encephalopathy, Cirrhosis
- Being tested
- Fecal transplant
- Keywords
- hepatic encephalopathy, fecal transplant, cirrhosis
- Medical subject headings
- Hepatic Encephalopathy, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fecal transplantBiological
| Study group | Role | What they receive |
|---|---|---|
| FMT | Active comparator | Fecal transplant via enema once Receives: Biological: Fecal transplant |
| No treatment | No intervention | No transplant performed |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability
Defined by the rate of development of FMT-related SAE and withdrawal from the study in cirrhotic subjects
Measured: 5 months
Secondary outcomes (2)
Microbiota composition and function
Deep sequencing of the microbiota and urinary metabolomics at baseline and post-FMT
Measured: 15 days
Cognitive functioning
Computerized and paper-pencil test battery
Measured: 15 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2015 (estimated)
- Study startOct 2015
- Primary completionAug 2016
- Study completionAug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatic EncephalopathyStudies 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jasmohan Bajaj
- Sponsor type
- US federal agency
- Collaborators
- OpenBiome
- Responsible party
- Sponsor-investigator, Jasmohan Bajaj, Hunter Holmes Mcguire Veteran Affairs Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02636647
- Sponsor's protocol ID
- BAJAJ0021
- Status last verified
- Jun 2022
- First submitted
- 16 Dec 2015
- Last updated
- 5 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Tolerability of Fecal Microbiota Transplantation in Cirrhosis and Hepatic Encephalopathy
- ClinicalTrials.gov ID
- NCT02636647
- Acronym / sponsor ID
- BAJAJ0021
- Conditions
- Hepatic Encephalopathy, Cirrhosis
- Keywords
- hepatic encephalopathy, fecal transplant, cirrhosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Jasmohan BajajUS federal agency
- Collaborators
- OpenBiome
- Study start
- Oct 2015
- Primary completion
- Aug 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 22 Dec 2015 (estimated)
- 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.
Randomized, open-label 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.
Detailed description
Group 1 (FMT group) will undergo the following procedures
Pre-FMT preparation:
We will obtain written informed consent per the IRB guidelines. After the patients are consented and are eligible, we will perform a detailed medical history and physical exam at day 0. We will also perform cognitive testing. As in prior studies, we will prescribe patients an antibiotic regimen. Drawing from ecological principles of microbial niche environments and data from recurrent Clostridium difficile infection, pre-treatment antibiotics are likely to increase the probability of disrupting the hosts intrinsic microbiota and creating an opportunity for a 'healthy' microbiota from the FMT to engraft.
After antibiotics and on the day of FMT:
At day 5, we will re-evaluate patients with a directed interval history and focused physical exam as needed. After ensuring that they are still candidates according to the inclusion/exclusion criteria, we will collect stool, urine and blood again for pre-FMT evaluation and urine for pregnancy tests from eligible women. Cognitive testing will be performed again.
Preparation and handling of stool for FMT infusion
Standard protocol for handling bio-hazardous material will be employed in order to avoid contamination and risk to healthcare handlers. Sterile microbiological technique will be employed during material transfer peri-procedure.
At that point we will provide the fecal material using universal precautions to a standard retention enema bag. The procedure will be completed by a trained Registered Nurse, Nurse practitioner, or physician in an outpatient clinic, endoscopy recovery area, or standard endoscopy unit.
The following will be recorded in all FMTs
- Dose
- Unit ID/Lot# of each treatment
- Expiration Date
- Storage Condition
- FMT retention time (in minutes)
Number of FMT: One administration Duration of Follow-up after FMT: 5 months
Follow-up after FMT:
We will see the patient in clinic the day following FMT (day 6 or FMT+1), day 12 (FMT+7), day 20 (FMT+15), and day 35 (FMT+30), at which point a detailed history regarding abdominal symptoms, evaluation of infectious complications, hospitalizations or complications of cirrhosis.
Visits on day 6, day 12 and day 35 will be purely safety associated while, on the day 20 visit, we will repeat the pathophysiological studies.
In order to ensure that we have enough samples, in case patients are not able to return at day 20, we will also collect all samples at day 12, but will only analyze them in case the day 20 visit does not occur.
These visits, apart from the visit after FMT, will be ±2 days for patient convenience.
At 5 months post-FMT, subjects will be followed up with a phone call to evaluate potential SAEs, new onset of transmitted infections, new onset or significant worsening of chronic medical conditions or suspected unexpected serious adverse reactions that have occurred in between 35 days and 5 months for reporting purposes.
Samples collected at baseline (before FMT), after antibiotics and at day 15 will be:
- Stool
- Blood
- Urine
Group 2: No treatment arm The group 2 will undergo all sample collections, follow-up and cognitive testing as in group 1 but without the 5-day antibiotic therapy or the FMT. In addition, we will also not perform the sample collection that is done after 5 days of antibiotics in this group since no reasonable change in microbiota are expected over 5 days without antibiotics. The follow-up of this group will be same as that of the FMT group.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FMT | Active comparator | Biological: Fecal transplantFecal transplant via enema once |
| No treatment | No intervention | –No transplant performed |
Who may qualify
- Ages
- 21 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Cirrhosis diagnosed by either of the following in a patient with chronic liver disease
- At least two episodes of hepatic encephalopathy, one within the last year but not within the last month (patient can be on lactulose and rifaximin)
- Age between 21 and 75
- Able to give written, informed consent (demonstrated by mini-mental status exam>25 at the time of consenting)
Key exclusion criteria (32 listed)
- MELD score >17
- WBC count <1000 cells/mm3
- Platelet count<50,000/mm3
- On the liver transplant list
- TIPS in place
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 transplant | Biological | FMT |
Primary outcome
Safety and tolerability
Time frame: 5 months
Defined by the rate of development of FMT-related SAE and withdrawal from the study in cirrhotic subjects
2 secondary outcomes
Microbiota composition and function
Time frame: 15 days
Cognitive functioning
Time frame: 15 days
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 5 Jul 2022.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 transplant in people with Hepatic Encephalopathy and Cirrhosis, run by Jasmohan Bajaj 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 8 inclusion and 32 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 5 Jul 2022. 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. 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?
Safety and tolerability (time frame: 5 months). 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 5 Jul 2022.