Oral Fecal Transplant in Cirrhosis
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|ClinicalTrials.gov Identifier: NCT03152188|
Recruitment Status : Completed
First Posted : May 12, 2017
Last Update Posted : May 19, 2021
|Condition or disease||Intervention/treatment||Phase|
|Hepatic Encephalopathy Cirrhosis, Liver||Drug: FMT Other: Placebo||Phase 1|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Placebo-controlled single-blind randomized trial|
|Masking:||Double (Participant, Outcomes Assessor)|
|Masking Description:||Single-blind study in which subjects will not be aware whether they will be on placebo or FMT capsulres|
|Official Title:||Modulation of Gut-Brain Axis Using Fecal Transplant Capsules in Cirrhosis|
|Actual Study Start Date :||June 12, 2017|
|Actual Primary Completion Date :||November 12, 2018|
|Actual Study Completion Date :||November 12, 2018|
Fecal Microbiota Transplantation (FMT) capsules
Fifteen FMT Openbiome capsules administered at the same time
Placebo Comparator: Placebo
Fifteen placebo capsules administered at the same time
- Serious Adverse events related to FMT [ Time Frame: 5 months ]Safety
- Frequency, severity and relatedness of solicited and unsolicited AEs [ Time Frame: 5 months ]Safety
- Occurrence of new potentially transmitted infections in the FMT group [ Time Frame: 5 months ]Safety
- Occurrence of new onset or significant worsening of chronic medical conditions post-FMT [ Time Frame: 5 months ]Safety
- 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 ]Mechanism
- 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 ]Mechanism
- cognitive function after oral FMT compared to pre-FMT baseline and compared to placebo [ Time Frame: 30 days ]Mechanism
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): NCT03152188
|United States, Virginia|
|Hunter Holmes McGuire VA Medical Center|
|Richmond, Virginia, United States, 23249|
|Virginia Commonwealth University|
|Richmond, Virginia, United States, 23298|
|Principal Investigator:||Jasmohan Bajaj, MD||Virginia Commonwealth University|