Acute Alcoholic Hepatitis
Conditions
Keywords
Alcoholic Hepatitis, MELD < 20, Probiotic, Nutritional Supplement, Lactobacillus Rhamnosus GG
Brief summary
This study is being done to find out whether a diet supplemented with a probiotic nutrient can improve alcoholic hepatitis and gut complications compared to routine standard care.
Detailed description
Aim 1: Evaluate the effects of probiotic supplements on improvement in MELD score and gut mucosal integrity in patients with MELD \< 21. Patients will be randomized to receive daily probiotics for 6 months and standard of care treatment or placebo with standard care. Aim 2: Document the natural history of moderately severe alcoholic hepatitis. Patients who decline randomization will be offered the option of inclusion in the study prospectively for data collection purposes and research study procedures. Aim 3: Create a data and tissue biorepository. This biorepository will serve as a national resource for studies related to acute alcoholic hepatitis.
Interventions
DIETARY_SUPPLEMENTLactobacillus Rhamnosus GG
Probiotic nutritional supplement; Lactobacillus Rhamnosus GG
Capsule manufactured without active ingredients.
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
The Cleveland Clinic
University of Massachusetts, Worcester
University of Louisville
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Ability to provide informed consent by subject or appropriate family member 2. Age between 21-70 years 3. Recent alcohol consumption \> 50 g/d for \> 6 months, continuing within two months before enrollment 4. At least 2 of the following symptoms or signs of acute alcoholic hepatitis: Anorexia, nausea, RUQ pain, jaundice, leukocytosis, hepatomegaly AND 5. Elevation of AST \> 80 U/L, but \< 500 U/L at the time of admission or within 3 days of baseline visit; AST \> ALT and ALT \< 200 U/L; total bilirubin \> 3 mg/dL AND 6. Liver biopsy showing alcoholic hepatitis (steatohepatitis) OR ultrasound of liver showing increased echogenicity OR CT scan showing decreased attenuation of liver compared to spleen OR MRI showing fatty liver (decreased signaling intensity on T1 weighted images). If the liver biopsy (done within 60 days of inclusion) confirms diagnosis of AAH then inclusion e will be waived. 7. Model for End-Stage Liver Disease (MELD) \<20 8. Willingness to utilize two reliable forms of contraception (both males and females of childbearing potential) from screening through the first six weeks of study.
Exclusion criteria
1. Hypotension with BP \< 80/50 after volume repletion 2. Pregnancy; incarceration; inability to provide consent or lack of appropriate family member 3. Signs of systemic infection: Fever \> 38o C and positive blood or ascites cultures on appropriate antibiotic therapy for \> 3 days within 3 days of inclusion 4. Acute gastrointestinal bleeding requiring \> 2 units blood transfusion within the previous 4 days 5. Undue risk from immunosuppression: Positive HBsAg; a positive skin PPD skin test or history of treatment for tuberculosis; history of any malignancy including hepatocellular carcinoma; known HIV infection 6. Treatment with corticosteroids or other immunosuppressive medications including specific anti-TNF therapy (not including pentoxifylline), calcineurin inhibitors for \> 3 days within the previous 3 months. 7. Evidence of acute pancreatitis: CT evidence and/or amylase or lipase \> 5 X upper limit of normal 8. Serious cardiac, respiratory or neurologic disease or evidence of autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, Wilsons disease, hemochromatosis, secondary iron overload due to chronic hemolysis, alpha-1-antitrypsin deficiency 9. Acute or chronic kidney injury with serum creatinine \> 3.0 mg/dl
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MELD Score | 30 days | Change in MELD scoring system for assessing the severity of chronic liver disease; MELD (Model of End Stage Liver Disease) scoring system for assessing the severity of chronic liver disease; calculated from serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time (INR) MELD = 3.8\[Ln serum bilirubin (mg/dL)\] + 11.2\[Ln INR\] + 9.6\[Ln serum creatinine (mg/dL)\] + 6.4. MELD score range from 6-40 with higher scores indicating more severe liver disease and a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MELD Score | 180 days | Change in MELD scoring system over 180 day study duration. MELD (Model of End Stage Liver Disease) scoring system for assessing the severity of chronic liver disease; calculated from serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time (INR) MELD = 3.8\[Ln serum bilirubin (mg/dL)\] + 11.2\[Ln INR\] + 9.6\[Ln serum creatinine (mg/dL)\] + 6.4. MELD score range from 6-40 with higher scores indicating more severe liver disease and a worse outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lactobacillus Rhamnosus GG Dietary supplement capsule (Lactobacillus Rhamnosus GG) will be given once daily for 180 days.
Lactobacillus Rhamnosus GG: Probiotic nutritional supplement; Lactobacillus Rhamnosus GG | 24 |
| Placebo for Probiotic Placebo capsule that matches the probiotic capsule in appearance will be given once daily for 180 days.
Placebo for Probiotic: Capsule manufactured without active ingredients. | 21 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Lost to Follow-up | 5 | 11 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo for Probiotic | Total | Lactobacillus Rhamnosus GG |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 45 Participants | 24 Participants |
| Age, Continuous | 45.0 years STANDARD_DEVIATION 9.4 | 44.6 years STANDARD_DEVIATION 10.7 | 44.2 years STANDARD_DEVIATION 12 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 18 Participants | 41 Participants | 23 Participants |
| Region of Enrollment United States | 21 participants | 45 participants | 24 participants |
| Sex: Female, Male Female | 11 Participants | 20 Participants | 9 Participants |
| Sex: Female, Male Male | 10 Participants | 25 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 1 / 21 |
| other Total, other adverse events | 16 / 24 | 15 / 21 |
| serious Total, serious adverse events | 17 / 24 | 15 / 21 |
Outcome results
Primary
MELD Score
Change in MELD scoring system for assessing the severity of chronic liver disease; MELD (Model of End Stage Liver Disease) scoring system for assessing the severity of chronic liver disease; calculated from serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time (INR) MELD = 3.8\[Ln serum bilirubin (mg/dL)\] + 11.2\[Ln INR\] + 9.6\[Ln serum creatinine (mg/dL)\] + 6.4. MELD score range from 6-40 with higher scores indicating more severe liver disease and a worse outcome.
Time frame: 30 days
Population: Four subjects from the LGG group and 8 subjects from the placebo group were lost to follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lactobacillus Rhamnosus GG | MELD Score | 14.25 score on a scale | Standard Deviation 3.88 |
| Placebo for Probiotic | MELD Score | 14.92 score on a scale | Standard Deviation 6.08 |
Secondary
MELD Score
Change in MELD scoring system over 180 day study duration. MELD (Model of End Stage Liver Disease) scoring system for assessing the severity of chronic liver disease; calculated from serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time (INR) MELD = 3.8\[Ln serum bilirubin (mg/dL)\] + 11.2\[Ln INR\] + 9.6\[Ln serum creatinine (mg/dL)\] + 6.4. MELD score range from 6-40 with higher scores indicating more severe liver disease and a worse outcome.
Time frame: 180 days
Population: 14 subjects from the LGG group and 17 subjects from the placebo group were lost to follow up by 180 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lactobacillus Rhamnosus GG | MELD Score | 11.0 score on a scale | Standard Deviation 5.46 |
| Placebo for Probiotic | MELD Score | 10.50 score on a scale | Standard Deviation 3.11 |
Secondary
MELD Score
Change in MELD scoring system at 90 days study duration. MELD (Model of End Stage Liver Disease) scoring system for assessing the severity of chronic liver disease; calculated from serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time (INR) MELD = 3.8\[Ln serum bilirubin (mg/dL)\] + 11.2\[Ln INR\] + 9.6\[Ln serum creatinine (mg/dL)\] + 6.4. MELD score range from 6-40 with higher scores indicating more severe liver disease and a worse outcome.
Time frame: 90 days
Population: 11 subjects from the LGG group and 16 subjects from the placebo group were lost to follow up by 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lactobacillus Rhamnosus GG | MELD Score | 11.62 score on a scale | Standard Deviation 8.41 |
| Placebo for Probiotic | MELD Score | 10.20 score on a scale | Standard Deviation 3.89 |