Hepatic EncephalopathyPhase 1NCT03152188
Oral Fecal Transplant in Cirrhosis
A Phase 1 study testing FMT in people with Hepatic Encephalopathy and Cirrhosis, Liver, run by Virginia Commonwealth University at 2 sites in United States.
Trial summary
To evaluate the safety and tolerability of oral fecal transplant in patients with cirrhosis and hepatic encephalopathy Read more about this study
- Who is it for?
- Ages 21 to 75 years
- Conditions the study is for
- Hepatic Encephalopathy, Cirrhosis, Liver
- What is being tested?
- FMT
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 2 sitesUnited States
- Study dates
- 12 Jun 2017to 12 Nov 2018
- 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
- 21-75 years of age
- Cirrhosis diagnosed by either of the following in a patient with chronic liver disease (a) Liver Biopsy (b) Radiologic evidence of varices, cirrhosis or portal hypertension (c) Laboratory evidence of platelet count <100,000 or AST/ALT ratio>1 (d) Endoscopic evidence of varices or portal gastropathy
- At least two HE episodes, one within the last year but not within the last month (patient can be on lactulose and rifaximin)
- Able to give written, informed consent (mini-mental status exam>25 at the time of consenting)
Who cannot join
- Disease-related: (1) MELD score>17 (2) WBC count<1000 (3) TIPS, non-elective hospitalization or HE within last month (4) on dialysis (5) known untreated, in-situ luminal GI cancers (6) chronic intrinsic GI diseases (ulcerative colitis, Crohn's disease or microscopic colitis, eosinophilic gastroenteritis and celiac disease) Endoscopy-related: (1) Platelet count<50,000 (2) adverse reactions to sedation (3) lack of driver or other contra-indications Safety-related: (1) Dysphagia (2) History of aspiration, gastroparesis, intestinal obstruction (3) Ongoing absorbable antibiotic use (4) Severe anaphylactic food allergy (5) allergy to ingredients Generally Recognized As Safe in the G3 capsules (glycerol, sodium chloride, hypromellose, gellan gum, titanium dioxide, theobroma oil) (6) Adverse event attributable to prior FMT (7) ASA Class IV or V (8) Pregnant or nursing patients (9) acute illness or fever on the day of planned FMT
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Hunter Holmes McGuire VA Medical Center
Richmond, Virginia, 23249
Virginia Commonwealth University
Richmond, Virginia, 23298
About this study
Official title: Modulation of Gut-Brain Axis Using Fecal Transplant Capsules in Cirrhosis
To evaluate the safety and tolerability of oral fecal transplant in patients with cirrhosis and hepatic encephalopathy
Read the detailed description
Hepatic encephalopathy affects 30-45% of patients with cirrhosis and adversely affects survival in these patients. The mainstay of treatment for hepatic encephalopathy (HE) has long been the manipulation of the gut microbiota through antibiotics, prebiotics or probiotics. The current first and second line therapies for HE in the US are lactulose and rifaximin respectively that uniquely act within the confines of the gut lumen with encouraging clinical results. However there is a subset of patients with HE that continues to recur despite being on both treatments. This patient group is at a higher risk of poor outcomes because HE has now been removed from liver transplant priority and multiple episodes of HE can result in cumulative brain injury which may be irreversible. Therefore the prevention of recurrent HE is an important therapeutic goal.
The study team's research and other reports have shown that patients with HE and cirrhosis are more likely to have overgrowth of potentially pathogenic bacterial taxa such as Enterobacteriaceae and reduction of autochthonous species such as Lachnospiraceae and Ruminococcaceae in the stool and the colonic mucosa. This has been linked to poor performance on cognitive tests that are a hallmark of HE and with increased systemic inflammation in these patients.
Therefore a gut-based therapeutic option that can potentially improve the recurrence rate and the overall prognosis is needed. Fecal transplant has been shown to be effective in conditions with predominant gut-bacterial overgrowth or alteration such as recurrent Clostridium difficile and inflammatory bowel disease. Safe protocols have been developed across the world and studies are being performed in the US under FDA-monitored INDs. Limitations to performing fecal transplant include identifying and screening appropriate donors, which is time consuming and costly, with the cost typically falling to the patient or donor as the required screening is generally not covered by insurance. For this reason, the study team is particularly interested in working with Openbiome and have obtained their collaboration towards performing this Fecal Microbiota Transplantation (FMT) by cross-referencing of their drug master file.
The preliminary data suggest that a one-time administration of an FMT-enema using a rationally-selected donor via Openbiome is safe in patients with cirrhosis and recurrent HE. However, given the small bowel overgrowth and the predominantly small bowel location for bacterial translocation in cirrhosis, which is out of the reach of an enema, an upper GI route for FMT needs to be explored. The FMT capsule by Openbiome acts on the small and large intestine and is available for C.difficile. It is potentially more acceptable to patients for repeated administrations and in cirrhosis has the advantage of acting on the small bowel in addition to the large bowel. The study will use a donor specifically selected from the Openbiome pool whose microbial profile best fulfils the microbiota deficits related to beneficial bacteria in HE patients, utilizing a "Precision Microbiome" approach.
- Conditions
- Hepatic Encephalopathy, Cirrhosis, Liver
- Being tested
- FMT, Placebo
- Keywords
- Hepatic Encephalopathy, Cirrhosis, Liver, Openbiome, FMT Capsule, Placebo
- Medical subject headings
- Hepatic Encephalopathy, Liver Cirrhosis, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FMTDrug
Fifteen FMT Openbiome capsules administered at the same time
PlaceboOther
Fifteen placebo capsules administered at the same time
| Study group | Role | What they receive |
|---|---|---|
| FMT | Experimental | Fecal Microbiota Transplantation (FMT) capsules Receives: Drug: FMT |
| Placebo | Placebo comparator | Placebo capsules Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serious Adverse events related to FMT
Safety
Measured: 5 months
Secondary outcomes (6)
Frequency, severity and relatedness of solicited and unsolicited AEs
Safety
Measured: 5 months
Occurrence of new potentially transmitted infections in the FMT group
Safety
Measured: 5 months
Occurrence of new onset or significant worsening of chronic medical conditions post-FMT
Safety
Measured: 5 months
changes in microbiota composition of the stool, duodenal and sigmoid colonic mucosa after oral FMT compared to pre-FMT baseline and donor compared to placebo post-FMT
Mechanism
Measured: 30 days
mucosal defenses by studying antimicrobial peptides, inflammatory cytokine expression and barrier protein expression compared to pre-FMT baseline and compared to placebo
Mechanism
Measured: 30 days
cognitive function after oral FMT compared to pre-FMT baseline and compared to placebo
Mechanism
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2017
- Study start12 Jun 2017
- Primary completion12 Nov 2018
- Study completion12 Nov 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hepatic EncephalopathyStudies of the same condition, open and under way.
- More trials run by Virginia Commonwealth UniversityThe sponsor's other registered studies.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Placebo-controlled single-blind randomized trial
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Collaborators
- OpenBiome, Medical College of Wisconsin, Hunter Holmes McGuire VA Medical Center, National Institutes of Health (NIH)
- Responsible party
- Sponsor
- Investigators
- Jasmohan Bajaj, MD, Principal investigator, Virginia Commonwealth University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03152188
- Sponsor's protocol ID
- HM20009392
- Other IDs
- 1R21TR002024
- Status last verified
- May 2021
- First submitted
- 11 May 2017
- Last updated
- 19 May 2021
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Bajaj JS, Salzman N, Acharya C, Takei H, Kakiyama G, Fagan A, White MB, Gavis EA, Holtz ML, Hayward M, Nittono H, Hylemon PB, Cox IJ, Williams R, Taylor-Robinson SD, Sterling RK, Matherly SC, Fuchs M, Lee H, Puri P, Stravitz RT, Sanyal AJ, Ajayi L, Le Guennec A, Atkinson RA, Siddiqui MS, Luketic V, Pandak WM, Sikaroodi M, Gillevet PM. Microbial functional change is linked with clinical outcomes after capsular fecal transplant in cirrhosis. JCI Insight. 2019 Dec 19;4(24):e133410. doi: 10.1172/jci.insight.133410.
PubMed 31751317Bajaj JS, Salzman NH, Acharya C, Sterling RK, White MB, Gavis EA, Fagan A, Hayward M, Holtz ML, Matherly S, Lee H, Osman M, Siddiqui MS, Fuchs M, Puri P, Sikaroodi M, Gillevet PM. Fecal Microbial Transplant Capsules Are Safe in Hepatic Encephalopathy: A Phase 1, Randomized, Placebo-Controlled Trial. Hepatology. 2019 Nov;70(5):1690-1703. doi: 10.1002/hep.30690. Epub 2019 Jun 18.
PubMed 31038755
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modulation of Gut-Brain Axis Using Fecal Transplant Capsules in Cirrhosis
- ClinicalTrials.gov ID
- NCT03152188
- Acronym / sponsor ID
- HM20009392
- Conditions
- Hepatic Encephalopathy, Cirrhosis, Liver
- Keywords
- Hepatic Encephalopathy, Cirrhosis, Liver, Openbiome, FMT Capsule, Placebo
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Collaborators
- OpenBiome, Medical College of Wisconsin, Hunter Holmes McGuire VA Medical Center, National Institutes of Health (NIH)
- Study start
- 12 Jun 2017 (actual)
- Primary completion
- 12 Nov 2018 (actual)
- Study completion
- 12 Nov 2018 (actual)
- First posted
- 12 May 2017 (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.
To evaluate the safety and tolerability of oral fecal transplant in patients with cirrhosis and hepatic encephalopathy
Detailed description
Hepatic encephalopathy affects 30-45% of patients with cirrhosis and adversely affects survival in these patients. The mainstay of treatment for hepatic encephalopathy (HE) has long been the manipulation of the gut microbiota through antibiotics, prebiotics or probiotics. The current first and second line therapies for HE in the US are lactulose and rifaximin respectively that uniquely act within the confines of the gut lumen with encouraging clinical results. However there is a subset of patients with HE that continues to recur despite being on both treatments. This patient group is at a higher risk of poor outcomes because HE has now been removed from liver transplant priority and multiple episodes of HE can result in cumulative brain injury which may be irreversible. Therefore the prevention of recurrent HE is an important therapeutic goal.
The study team's research and other reports have shown that patients with HE and cirrhosis are more likely to have overgrowth of potentially pathogenic bacterial taxa such as Enterobacteriaceae and reduction of autochthonous species such as Lachnospiraceae and Ruminococcaceae in the stool and the colonic mucosa. This has been linked to poor performance on cognitive tests that are a hallmark of HE and with increased systemic inflammation in these patients.
Therefore a gut-based therapeutic option that can potentially improve the recurrence rate and the overall prognosis is needed. Fecal transplant has been shown to be effective in conditions with predominant gut-bacterial overgrowth or alteration such as recurrent Clostridium difficile and inflammatory bowel disease. Safe protocols have been developed across the world and studies are being performed in the US under FDA-monitored INDs. Limitations to performing fecal transplant include identifying and screening appropriate donors, which is time consuming and costly, with the cost typically falling to the patient or donor as the required screening is generally not covered by insurance. For this reason, the study team is particularly interested in working with Openbiome and have obtained their collaboration towards performing this Fecal Microbiota Transplantation (FMT) by cross-referencing of their drug master file.
The preliminary data suggest that a one-time administration of an FMT-enema using a rationally-selected donor via Openbiome is safe in patients with cirrhosis and recurrent HE. However, given the small bowel overgrowth and the predominantly small bowel location for bacterial translocation in cirrhosis, which is out of the reach of an enema, an upper GI route for FMT needs to be explored. The FMT capsule by Openbiome acts on the small and large intestine and is available for C.difficile. It is potentially more acceptable to patients for repeated administrations and in cirrhosis has the advantage of acting on the small bowel in addition to the large bowel. The study will use a donor specifically selected from the Openbiome pool whose microbial profile best fulfils the microbiota deficits related to beneficial bacteria in HE patients, utilizing a "Precision Microbiome" approach.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Placebo-controlled single-blind randomized trial
| Arm | Type | Receives |
|---|---|---|
| FMT | Experimental | Drug: FMTFecal Microbiota Transplantation (FMT) capsules |
| Placebo | Placebo comparator | Other: PlaceboPlacebo capsules |
Who may qualify
- Ages
- 21 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 21-75 years of age
- Cirrhosis diagnosed by either of the following in a patient with chronic liver disease (a) Liver Biopsy (b) Radiologic evidence of varices, cirrhosis or portal hypertension (c) Laboratory evidence of platelet count <100,000 or AST/ALT ratio>1 (d) Endoscopic evidence of varices or portal gastropathy
- At least two HE episodes, one within the last year but not within the last month (patient can be on lactulose and rifaximin)
- Able to give written, informed consent (mini-mental status exam>25 at the time of consenting)
Key exclusion criteria (1 listed)
- Disease-related: (1) MELD score>17 (2) WBC count<1000 (3) TIPS, non-elective hospitalization or HE within last month (4) on dialysis (5) known untreated, in-situ luminal GI cancers (6) chronic intrinsic GI diseases (ulcerative colitis, Crohn's disease or microscopic colitis, eosinophilic gastroenteritis and celiac disease) Endoscopy-related: (1) Platelet count<50,000 (2) adverse reactions to sedation (3) lack of driver or other contra-indications Safety-related: (1) Dysphagia (2) History of aspiration, gastroparesis, intestinal obstruction (3) Ongoing absorbable antibiotic use (4) Severe anaphylactic food allergy (5) allergy to ingredients Generally Recognized As Safe in the G3 capsules (glycerol, sodium chloride, hypromellose, gellan gum, titanium dioxide, theobroma oil) (6) Adverse event attributable to prior FMT (7) ASA Class IV or V (8) Pregnant or nursing patients (9) acute illness or fever on the day of planned FMT
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 |
|---|---|---|
| FMTFifteen FMT Openbiome capsules administered at the same time | Drug | FMT |
| PlaceboFifteen placebo capsules administered at the same time | Other | Placebo |
Primary outcome
Serious Adverse events related to FMT
Time frame: 5 months
Safety
6 secondary outcomes
Frequency, severity and relatedness of solicited and unsolicited AEs
Time frame: 5 months
Occurrence of new potentially transmitted infections in the FMT group
Time frame: 5 months
Occurrence of new onset or significant worsening of chronic medical conditions post-FMT
Time frame: 5 months
changes in microbiota composition of the stool, duodenal and sigmoid colonic mucosa after oral FMT compared to pre-FMT baseline and donor compared to placebo post-FMT
Time frame: 30 days
mucosal defenses by studying antimicrobial peptides, inflammatory cytokine expression and barrier protein expression compared to pre-FMT baseline and compared to placebo
Time frame: 30 days
cognitive function after oral FMT compared to pre-FMT baseline and compared to placebo
Time frame: 30 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 19 May 2021.
- Derived from this study: PubMed 31751317Bajaj JS, Salzman N, Acharya C, Takei H, Kakiyama G, Fagan A, White MB, Gavis EA, Holtz ML, Hayward M, Nittono H, Hylemon PB, Cox IJ, Williams R, Taylor-Robinson SD, Sterling RK, Matherly SC, Fuchs M, Lee H, Puri P, Stravitz RT, Sanyal AJ, Ajayi L, Le Guennec A, Atkinson RA, Siddiqui MS, Luketic V, Pandak WM, Sikaroodi M, Gillevet PM. Microbial functional change is linked with clinical outcomes after capsular fecal transplant in cirrhosis. JCI Insight. 2019 Dec 19;4(24):e133410. doi: 10.1172/jci.insight.133410.
- Derived from this study: PubMed 31038755Bajaj JS, Salzman NH, Acharya C, Sterling RK, White MB, Gavis EA, Fagan A, Hayward M, Holtz ML, Matherly S, Lee H, Osman M, Siddiqui MS, Fuchs M, Puri P, Sikaroodi M, Gillevet PM. Fecal Microbial Transplant Capsules Are Safe in Hepatic Encephalopathy: A Phase 1, Randomized, Placebo-Controlled Trial. Hepatology. 2019 Nov;70(5):1690-1703. doi: 10.1002/hep.30690. Epub 2019 Jun 18.
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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 Bajaj, MD principal investigator
Virginia Commonwealth University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing FMT in people with Hepatic Encephalopathy and Cirrhosis, Liver, run by Virginia Commonwealth University at 2 sites 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 4 inclusion and 1 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 19 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Serious Adverse events related to FMT (time frame: 5 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03152188, which also lists 2 linked publications.
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 19 May 2021.