Acute Alcoholic HepatitisNTAH-ModNCT01922895
Novel Therapies in Moderately Severe Acute Alcoholic Hepatitis
A study testing Lactobacillus Rhamnosus GG in people with Acute Alcoholic Hepatitis, run by University of Texas Southwestern Medical Center at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 70 years
- Conditions the study is for
- Acute Alcoholic Hepatitis
- What is being tested?
- Lactobacillus Rhamnosus GG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 3 sitesUnited States
- Study dates
- 1 Aug 2013to 31 Aug 2021
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to provide informed consent by subject or appropriate family member
- Age between 21-70 years
- Recent alcohol consumption > 50 g/d for > 6 months, continuing within two months before enrollment
- At least 2 of the following symptoms or signs of acute alcoholic hepatitis: Anorexia, nausea, RUQ pain, jaundice, leukocytosis, hepatomegaly AND
- 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
- 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.
- Model for End-Stage Liver Disease (MELD) <20
- Willingness to utilize two reliable forms of contraception (both males and females of childbearing potential) from screening through the first six weeks of study.
Who cannot join
- Hypotension with BP < 80/50 after volume repletion
- Pregnancy; incarceration; inability to provide consent or lack of appropriate family member
- 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
- Acute gastrointestinal bleeding requiring > 2 units blood transfusion within the previous 4 days
- 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
- 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.
Show all 9Show fewer
- Evidence of acute pancreatitis: CT evidence and/or amylase or lipase > 5 X upper limit of normal
- 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
- Acute or chronic kidney injury with serum creatinine > 3.0 mg/dl
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Cleveland Clinic
Cleveland, Ohio, 44195
U Texas Southwestern Medical Center
Dallas, Texas, 75390
University of Louisville
Louisville, Kentucky, 40202
About this study
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.
Read the 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.
- Conditions
- Acute Alcoholic Hepatitis
- Being tested
- Lactobacillus Rhamnosus GG, Placebo for Probiotic
- Keywords
- Alcoholic Hepatitis, MELD < 20, Probiotic, Nutritional Supplement, Lactobacillus Rhamnosus GG
- Medical subject headings
- Hepatitis, Alcoholic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lactobacillus Rhamnosus GGDietary supplement
Also called Culturelle
Probiotic nutritional supplement; Lactobacillus Rhamnosus GG
Placebo for ProbioticDrug
Also called Dummy capsule
Capsule manufactured without active ingredients.
| Study group | Role | What they receive |
|---|---|---|
| Placebo for Probiotic | Placebo comparator | Placebo capsule that matches the probiotic capsule in appearance will be given once daily for 180 days. Receives: Drug: Placebo for Probiotic |
| Lactobacillus Rhamnosus GG | Active comparator | Dietary supplement capsule (Lactobacillus Rhamnosus GG) will be given once daily for 180 days. Receives: Dietary Supplement: Lactobacillus Rhamnosus GG |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 30 days
Secondary outcomes (2)
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.
Measured: 180 days
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.
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2013 (estimated)
- Study start1 Aug 2013
- Primary completion1 Jul 2018
- Study completion31 Aug 2021
Why it stopped: Lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute Alcoholic HepatitisStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe 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 N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA), The Cleveland Clinic, University of Massachusetts, Worcester, University of Louisville
- Responsible party
- Principal investigator, Mack Mitchell, University of Texas Southwestern Medical Center
- Investigators
- Mack C Mitchell, M.D., Principal investigator, U Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01922895
- Sponsor's protocol ID
- STU 092012-012
- Other IDs
- U01AA021893-01
- Acronym
- NTAH-Mod
- Status last verified
- Feb 2022
- First submitted
- 12 Aug 2013
- Last updated
- 2 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Vatsalya V, Feng W, Kong M, Hu H, Szabo G, McCullough A, Dasarathy S, Nagy LE, Radaeva S, Barton B, Mitchell M, McClain CJ. The Beneficial Effects of Lactobacillus GG Therapy on Liver and Drinking Assessments in Patients with Moderate Alcohol-Associated Hepatitis. Am J Gastroenterol. 2023 Aug 1;118(8):1457-1460. doi: 10.14309/ajg.0000000000002283. Epub 2023 Apr 11.
PubMed 37040544Vatsalya V, Cave MC, Kong M, Gobejishvili L, Falkner KC, Craycroft J, Mitchell M, Szabo G, McCullough A, Dasarathy S, Radaeva S, Barton B, McClain CJ. Keratin 18 Is a Diagnostic and Prognostic Factor for Acute Alcoholic Hepatitis. Clin Gastroenterol Hepatol. 2020 Aug;18(9):2046-2054. doi: 10.1016/j.cgh.2019.11.050. Epub 2019 Dec 4.
PubMed 31811953
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Therapies in Moderately Severe Acute Alcoholic Hepatitis
- ClinicalTrials.gov ID
- NCT01922895
- Acronym / sponsor ID
- NTAH-Mod / STU 092012-012
- Conditions
- Acute Alcoholic Hepatitis
- Keywords
- Alcoholic Hepatitis, MELD < 20, Probiotic, Nutritional Supplement, Lactobacillus Rhamnosus GG
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of funding
- Enrolment
- 45 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA), The Cleveland Clinic, University of Massachusetts, Worcester, University of Louisville
- Study start
- 1 Aug 2013 (actual)
- Primary completion
- 1 Jul 2018 (actual)
- Study completion
- 31 Aug 2021 (actual)
- First posted
- 14 Aug 2013 (estimated)
- Results
- Posted 2 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo for Probiotic | Placebo comparator | Drug: Placebo for ProbioticPlacebo capsule that matches the probiotic capsule in appearance will be given once daily for 180 days. |
| Lactobacillus Rhamnosus GG | Active comparator | Dietary Supplement: Lactobacillus Rhamnosus GGDietary supplement capsule (Lactobacillus Rhamnosus GG) will be given once daily for 180 days. |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Ability to provide informed consent by subject or appropriate family member
- Age between 21-70 years
- Recent alcohol consumption > 50 g/d for > 6 months, continuing within two months before enrollment
- At least 2 of the following symptoms or signs of acute alcoholic hepatitis: Anorexia, nausea, RUQ pain, jaundice, leukocytosis, hepatomegaly AND
- 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
Key exclusion criteria (9 listed)
- Hypotension with BP < 80/50 after volume repletion
- Pregnancy; incarceration; inability to provide consent or lack of appropriate family member
- 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
- Acute gastrointestinal bleeding requiring > 2 units blood transfusion within the previous 4 days
- 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
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 |
|---|---|---|
| Lactobacillus Rhamnosus GGAlso: CulturelleProbiotic nutritional supplement; Lactobacillus Rhamnosus GG | Dietary supplement | Lactobacillus Rhamnosus GG |
| Placebo for ProbioticAlso: Dummy capsuleCapsule manufactured without active ingredients. | Drug | Placebo for Probiotic |
Primary outcome
MELD Score
Time frame: 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.
2 secondary outcomes
MELD Score
Time frame: 180 days
MELD Score
Time frame: 90 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37040544Vatsalya V, Feng W, Kong M, Hu H, Szabo G, McCullough A, Dasarathy S, Nagy LE, Radaeva S, Barton B, Mitchell M, McClain CJ. The Beneficial Effects of Lactobacillus GG Therapy on Liver and Drinking Assessments in Patients with Moderate Alcohol-Associated Hepatitis. Am J Gastroenterol. 2023 Aug 1;118(8):1457-1460. doi: 10.14309/ajg.0000000000002283. Epub 2023 Apr 11.
- Derived from this study: PubMed 31811953Vatsalya V, Cave MC, Kong M, Gobejishvili L, Falkner KC, Craycroft J, Mitchell M, Szabo G, McCullough A, Dasarathy S, Radaeva S, Barton B, McClain CJ. Keratin 18 Is a Diagnostic and Prognostic Factor for Acute Alcoholic Hepatitis. Clin Gastroenterol Hepatol. 2020 Aug;18(9):2046-2054. doi: 10.1016/j.cgh.2019.11.050. Epub 2019 Dec 4.
- Individual participant dataSharing planned: No
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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.
Mack C Mitchell, M.D. principal investigator
U Texas Southwestern Medical Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lactobacillus Rhamnosus GG in people with Acute Alcoholic Hepatitis, run by University of Texas Southwestern Medical Center at 3 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 8 inclusion and 9 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: stopped early, as of the sponsor's last update on 2 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
MELD Score (time frame: 30 days). 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 NCT01922895, 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 2 Mar 2022.