Ignite Creation Date:
2024-05-06 @ 12:34 PM
Last Modification Date:
2024-10-26 @ 1:01 PM
Study NCT ID:
NCT03796598
Status:
COMPLETED
Last Update Posted:
2023-12-28
First Post:
2019-01-03
Brief Title:
FMT in Cirrhosis and Hepatic Encephalopathy
Sponsor:
VA Office of Research and Development
Organization:
VA Office of Research and Development
Study Overview
Official Title:
Fecal Microbiota Transplant in Veterans With Cirrhosis
Status:
COMPLETED
Status Verified Date:
2023-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 persons 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 HE and related 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
Detailed Description:
Indication Cirrhosis and hepatic encephalopathy
Study Objectives To evaluate the safety and tolerability of fecal transplant in patients with cirrhosis and hepatic encephalopathy
Rationale and Supporting Evidence
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 flora 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 investigators group 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
The investigators preliminary data suggest that a one-time administration of an FMT-enema using a rationally-selected donor 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 In the investigators published experience a single enema from a rationally-derived donor was associated with significantly lower total and HE-related hospitalizations compared to patients who were randomized to standard of care with a stable long-term course over 1 year The investigators data show that FMT was associated with favorable changes in fecal bile acid BA profile with a decrease in proportions of fecal secondary BAs conjugated BAs and increase in sulfated BAs indicating a healthier milieu The investigators also have preliminary data defining the safety of oral FMT capsules in patients with cirrhosis and HE in a current trial led by us The use of combined oral and rectal routes of FMT which can potentially alleviate both small bowel and colonic translocation are likely to be better than either alone
Overall aim To determine the effect of dual oral and rectal administration of FMT from a rational donor on clinical outcomes HE and related hospitalizations brain function quality of life and host-microbiota interactions microbial composition and bile acid composition with systemic and intestinal inflammation compared to single route of administration and placebo along with a second oral capsular FMT vs placebo administration in patients with cirrhosis and HE using a randomized phase II clinical trial
Design overview Four groups of outpatients with cirrhosis will be randomized using random sequence generator into placebo and FMT groups and followed for 6 months under an FDA IND double-blind clinical trial
Study Objectives To evaluate the safety and tolerability of fecal transplant in patients with cirrhosis and hepatic encephalopathy
Rationale and Supporting Evidence
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 flora 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 investigators group 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
The investigators preliminary data suggest that a one-time administration of an FMT-enema using a rationally-selected donor 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 In the investigators published experience a single enema from a rationally-derived donor was associated with significantly lower total and HE-related hospitalizations compared to patients who were randomized to standard of care with a stable long-term course over 1 year The investigators data show that FMT was associated with favorable changes in fecal bile acid BA profile with a decrease in proportions of fecal secondary BAs conjugated BAs and increase in sulfated BAs indicating a healthier milieu The investigators also have preliminary data defining the safety of oral FMT capsules in patients with cirrhosis and HE in a current trial led by us The use of combined oral and rectal routes of FMT which can potentially alleviate both small bowel and colonic translocation are likely to be better than either alone
Overall aim To determine the effect of dual oral and rectal administration of FMT from a rational donor on clinical outcomes HE and related hospitalizations brain function quality of life and host-microbiota interactions microbial composition and bile acid composition with systemic and intestinal inflammation compared to single route of administration and placebo along with a second oral capsular FMT vs placebo administration in patients with cirrhosis and HE using a randomized phase II clinical trial
Design overview Four groups of outpatients with cirrhosis will be randomized using random sequence generator into placebo and FMT groups and followed for 6 months under an FDA IND double-blind clinical trial
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| CX001076 | OTHER_GRANT | Office of Research and Development VA | None |