Fecal Microbiota Transplant as Treatment of Hepatic Encephalopathy
| Status: | Recruiting |
|---|---|
| Conditions: | Neurology, Gastrointestinal |
| Therapuetic Areas: | Gastroenterology, Neurology |
| Healthy: | No |
| Age Range: | 18 - 75 |
| Updated: | 3/13/2019 |
| Start Date: | April 1, 2018 |
| End Date: | January 31, 2021 |
| Contact: | Patricia L Pringle, MD |
| Email: | ppringle@partners.org |
| Phone: | 978-460-0538 |
A common complication of advanced liver disease is a condition called hepatic encephalopathy,
which leads to confusion. The current treatment options cause side effects, are costly, and
do not always work. An abnormal population of bacteria in the intestines may be causing this
condition, and transplanting bacteria from the colon of a healthy person may treat it. In
this research study, the investigators will first find two healthy stool donors whose stool
donation improves the gut bacteria of patients with advanced liver disease and helps them
think more clearly. Then, in a randomized controlled trial, the investigators will compare
the ability of stool donation from these two best donors versus a placebo to improve the
neurological function of patients with advanced liver disease. If the investigators find the
expected results, there will be a new effective therapy for patients with advanced liver
disease and the very troublesome complication of hepatic encephalopathy.
which leads to confusion. The current treatment options cause side effects, are costly, and
do not always work. An abnormal population of bacteria in the intestines may be causing this
condition, and transplanting bacteria from the colon of a healthy person may treat it. In
this research study, the investigators will first find two healthy stool donors whose stool
donation improves the gut bacteria of patients with advanced liver disease and helps them
think more clearly. Then, in a randomized controlled trial, the investigators will compare
the ability of stool donation from these two best donors versus a placebo to improve the
neurological function of patients with advanced liver disease. If the investigators find the
expected results, there will be a new effective therapy for patients with advanced liver
disease and the very troublesome complication of hepatic encephalopathy.
Decades of investigation demonstrate that hepatic encephalopathy (HE), a common complication
of cirrhosis characterized by impaired cognition, develops as a consequence of intestinal
microbial products reaching the brain. Recent investigation has found that cirrhotic
patients, especially those who have developed HE, have intestinal dysbiosis compared to
normal controls. Several plausible mechanisms explain how intestinal dysbiosis could lead to
HE. There is limited prior literature on the efficacy of FMT in cirrhosis. The largest
documented study of 10 cirrhotic patients receiving a single FMT enema found no significant
change in microbiome diversity as assessed by 16S rRNA sequencing. The investigators
hypothesize that aggressive manipulation of the microbial composition with fecal microbiota
transplant (FMT) will improve neurological function in patients with a history of cirrhosis
and HE. The investigators additionally hypothesize that five oral FMT capsule administrations
from a previously efficacious stool donor will significantly change the intestinal microbiome
composition of a cirrhotic patient. The study will consist of a 10-patient open-label pilot
study to identify efficacious stool donors, defined as donors who precipitate the largest
improvement in recipient neurological function and microbiome composition. The two most
efficacious pilot study stool donors will be selected to donate stool for the randomized
controlled trial (RCT). The 20-patient RCT will investigate the effect of FMT on neurological
outcomes in patients with cirrhosis and a history of HE. Subjects will be randomized to
receive 5 doses of oral FMT capsules or placebo capsules over 21 days. Cognitive testing and
stool collections will occur at 4 time points, to assess for changes in neurological function
and microbiome composition. The primary outcome is change in neurological function after FMT.
The main secondary outcome is change in microbiome composition after FMT. This study could
provide valuable information about the ability of FMT to improve intestinal dysbiosis in
cirrhosis and treat HE.
of cirrhosis characterized by impaired cognition, develops as a consequence of intestinal
microbial products reaching the brain. Recent investigation has found that cirrhotic
patients, especially those who have developed HE, have intestinal dysbiosis compared to
normal controls. Several plausible mechanisms explain how intestinal dysbiosis could lead to
HE. There is limited prior literature on the efficacy of FMT in cirrhosis. The largest
documented study of 10 cirrhotic patients receiving a single FMT enema found no significant
change in microbiome diversity as assessed by 16S rRNA sequencing. The investigators
hypothesize that aggressive manipulation of the microbial composition with fecal microbiota
transplant (FMT) will improve neurological function in patients with a history of cirrhosis
and HE. The investigators additionally hypothesize that five oral FMT capsule administrations
from a previously efficacious stool donor will significantly change the intestinal microbiome
composition of a cirrhotic patient. The study will consist of a 10-patient open-label pilot
study to identify efficacious stool donors, defined as donors who precipitate the largest
improvement in recipient neurological function and microbiome composition. The two most
efficacious pilot study stool donors will be selected to donate stool for the randomized
controlled trial (RCT). The 20-patient RCT will investigate the effect of FMT on neurological
outcomes in patients with cirrhosis and a history of HE. Subjects will be randomized to
receive 5 doses of oral FMT capsules or placebo capsules over 21 days. Cognitive testing and
stool collections will occur at 4 time points, to assess for changes in neurological function
and microbiome composition. The primary outcome is change in neurological function after FMT.
The main secondary outcome is change in microbiome composition after FMT. This study could
provide valuable information about the ability of FMT to improve intestinal dysbiosis in
cirrhosis and treat HE.
Inclusion Criteria:
- Diagnosis of cirrhosis: Based on liver biopsy or clinical assessment of a hepatologist
based on history, exam, laboratory and radiographic evidence
- History of at least one episode of overt HE, defined by West Haven Criteria Grades II
to IV; episodes of HE that were precipitated by gastrointestinal hemorrhage requiring
transfusion of at least 2 units of blood, by medication use, by renal failure
requiring dialysis, or by injury to the central nervous system will not be counted as
previous HE episodes
- Compliant with lactulose and rifaximin treatment (lactulose: at least one dose at
least 5 days per week; rifaximin: at least one dose at least 5 days per week)
Exclusion Criteria:
- Current episode of overt HE as defined by West Haven Criteria Grades II to IV
- Expectation of liver transplantation within two months of the screening visit
- Current infection
- Variceal bleeding in the last 4 weeks
- Gut-absorbable or intravenous antibiotic therapy (including ciprofloxacin for SBP
prophylaxis) in the last 3 months
- Alcohol or illicit drug intake within 3 months, by history and available serum
testing; alcohol use will be characterized as >1 alcoholic drink / month
- PSC as etiology of liver disease, as prior literature has suggested these individuals
have a unique microbiome
- History of Roux-en-Y Gastric bypass
- On immunosuppressive medications
- Positive C. difficile test
- Scoring above a threshold cut-off on the Psychometric Hepatic Encephalopathy Score
(PHES)
- MELD > 20
- Hemodialysis in the last 30 days
- Other significant laboratory abnormalities: serum creatinine > 2.0 mg/dL, hemoglobin <
8 g/dL, serum sodium < 125 mmol/L, serum calcium > 11.0 mg/dL, serum potassium < 2.5
mmol/L
- Placement of a portosystemic shunt or transjugular intrahepatic portosystemic shunt
- Unstable doses of opiates, benzodiazepines or other sedating medication
- Unable to provide consent; if MMSE is < 18 or the patient is deemed to not have
capacity by an investigator, a legally authorized representative (surrogate) will be
allowed to provide consent
We found this trial at
1
site
185 Cambridge Street
Boston, Massachusetts 02114
Boston, Massachusetts 02114
617-724-5200
Phone: 978-460-0538
Click here to add this to my saved trials
