Novel Therapies in Moderately Severe Acute Alcoholic Hepatitis (NTAH-Mod)

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ClinicalTrials.gov Identifier: NCT01922895

Recruitment Status : Terminated (Lack of funding)

First Posted : August 14, 2013

Results First Posted : March 2, 2022

Last Update Posted : March 2, 2022

Sponsor:

Collaborators:

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

The Cleveland Clinic

University of Massachusetts, Worcester

University of Louisville

Information provided by (Responsible Party):

Mack Mitchell, University of Texas Southwestern Medical Center

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Other
Condition	Acute Alcoholic Hepatitis
Interventions	Dietary Supplement: Lactobacillus Rhamnosus GG Drug: Placebo for Probiotic
Enrollment	45

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Lactobacillus Rhamnosus GG	Placebo for Probiotic
Arm/Group Description	Dietary supplement capsule (Lactoba...	Placebo capsule that matches the pr...
Arm/Group Description	Dietary supplement capsule (Lactobacillus Rhamnosus GG) will be given once daily for 180 days. Lactobacillus Rhamnosus GG: Probiotic nutritional supplement; Lactobacillus Rhamnosus GG	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.
Period Title: Overall Study
Started	24	21
Completed	18	7
Not Completed	6	14
Reason Not Completed
Death	0	1
Withdrawal by Subject	1	2
Lost to Follow-up	5	11

Baseline Characteristics

Arm/Group Title		Lactobacillus Rhamnosus GG	Placebo for Probiotic	Total
Arm/Group Description		Dietary supplement capsule (Lactoba...	Placebo capsule that matches the pr...	Total of all reporting groups
Arm/Group Description		Dietary supplement capsule (Lactobacillus Rhamnosus GG) will be given once daily for 180 days. Lactobacillus Rhamnosus GG: Probiotic nutritional supplement; Lactobacillus Rhamnosus GG	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.	Total of all reporting groups
Overall Number of Baseline Participants		24	21	45
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	24 participants	21 participants	45 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	24 100.0%	21 100.0%	45 100.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	24 participants	21 participants	45 participants
		44.2 (12.0)	45.0 (9.4)	44.6 (10.7)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	24 participants	21 participants	45 participants
	Female	9 37.5%	11 52.4%	20 44.4%
	Male	15 62.5%	10 47.6%	25 55.6%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	24 participants	21 participants	45 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	1 4.8%	1 2.2%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	1 4.2%	2 9.5%	3 6.7%
	White	23 95.8%	18 85.7%	41 91.1%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment Measure Type: Number Unit of measure: Participants
United States	Number Analyzed	24 participants	21 participants	45 participants
United States		24	21	45

Outcome Measures

1.Primary Outcome


Title	MELD Score
Description	Change in MELD scoring system for assessing the severity of chronic li...
Description	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

Outcome Measure Data

Analysis Population Description

Four subjects from the LGG group and 8 subjects from the placebo group were lost to follow-up.


Arm/Group Title	Lactobacillus Rhamnosus GG	Placebo for Probiotic
Arm/Group Description:	Dietary supplement capsule (Lactoba...	Placebo capsule that matches the pr...
Arm/Group Description:	Dietary supplement capsule (Lactobacillus Rhamnosus GG) will be given once daily for 180 days. Lactobacillus Rhamnosus GG: Probiotic nutritional supplement; Lactobacillus Rhamnosus GG	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.
Overall Number of Participants Analyzed	20	13
Mean (Standard Deviation) Unit of Measure: score on a scale
	14.25 (3.88)	14.92 (6.08)

2.Secondary Outcome


Title	MELD Score
Description	Change in MELD scoring system over 180 day study duration. MELD (Model...
Description	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

Outcome Measure Data

Analysis Population Description

14 subjects from the LGG group and 17 subjects from the placebo group were lost to follow up by 180 days


Arm/Group Title	Lactobacillus Rhamnosus GG	Placebo for Probiotic
Arm/Group Description:	Dietary supplement capsule (Lactoba...	Placebo capsule that matches the pr...
Arm/Group Description:	Dietary supplement capsule (Lactobacillus Rhamnosus GG) will be given once daily for 180 days. Lactobacillus Rhamnosus GG: Probiotic nutritional supplement; Lactobacillus Rhamnosus GG	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.
Overall Number of Participants Analyzed	10	4
Mean (Standard Deviation) Unit of Measure: score on a scale
	11.0 (5.46)	10.50 (3.11)

3.Secondary Outcome


Title	MELD Score
Description	Change in MELD scoring system at 90 days study duration. MELD (Model o...
Description	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

Outcome Measure Data

Analysis Population Description

11 subjects from the LGG group and 16 subjects from the placebo group were lost to follow up by 90 days


Arm/Group Title	Lactobacillus Rhamnosus GG	Placebo for Probiotic
Arm/Group Description:	Dietary supplement capsule (Lactoba...	Placebo capsule that matches the pr...
Arm/Group Description:	Dietary supplement capsule (Lactobacillus Rhamnosus GG) will be given once daily for 180 days. Lactobacillus Rhamnosus GG: Probiotic nutritional supplement; Lactobacillus Rhamnosus GG	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.
Overall Number of Participants Analyzed	13	5
Mean (Standard Deviation) Unit of Measure: score on a scale
	11.62 (8.41)	10.20 (3.89)

Adverse Events

Time Frame	180 days
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Lactobacillus Rhamnosus GG	Placebo for Probiotic
Arm/Group Description	Dietary supplement capsule (Lactoba...	Placebo capsule that matches the pr...
Arm/Group Description	Dietary supplement capsule (Lactobacillus Rhamnosus GG) will be given once daily for 180 days. Lactobacillus Rhamnosus GG: Probiotic nutritional supplement; Lactobacillus Rhamnosus GG	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.
All-Cause Mortality
	Lactobacillus Rhamnosus GG	Placebo for Probiotic
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/24 (0.00%)	1/21 (4.76%)
Serious Adverse Events Serious Adverse Events
	Lactobacillus Rhamnosus GG	Placebo for Probiotic
	Affected / at Risk (%)	Affected / at Risk (%)
Total	17/24 (70.83%)	15/21 (71.43%)
Cardiac disorders
Ascites ^† 1	0/24 (0.00%)	1/21 (4.76%)
Gastrointestinal disorders
Vomiting ^† 1	0/24 (0.00%)	1/21 (4.76%)
General disorders
Multiple conditions defined for single event ^† 1	0/24 (0.00%)	3/21 (14.29%)
Hepatobiliary disorders
Hepatitis alcoholic ^† 1	1/24 (4.17%)	0/21 (0.00%)
Infections and infestations
Peritonitis ^† 1	1/24 (4.17%)	0/21 (0.00%)
Sepsis ^† 1	2/24 (8.33%)	0/21 (0.00%)
Metabolism and nutrition disorders
Alcohol intolerance ^† 1	0/24 (0.00%)	3/21 (14.29%)
Hyperglycaemia ^† 1	1/24 (4.17%)	0/21 (0.00%)
Hyponatraemia ^† 1	1/24 (4.17%)	2/21 (9.52%)
Renal and urinary disorders
Acute kidney injury ^† 1	9/24 (37.50%)	2/21 (9.52%)
Respiratory, thoracic and mediastinal disorders
Pneumonia ^† 1	0/24 (0.00%)	1/21 (4.76%)
Pneumonia bacterial ^† 1	0/24 (0.00%)	1/21 (4.76%)
Upper respiratory tract infection ^† 1	1/24 (4.17%)	0/21 (0.00%)
Vascular disorders
Rectal haemorrhage ^† 1	0/24 (0.00%)	1/21 (4.76%)
Vaginal haemorrhage ^† 1	1/24 (4.17%)	0/21 (0.00%)
1 Term from vocabulary, MedDRA Version 20.1 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Lactobacillus Rhamnosus GG	Placebo for Probiotic
	Affected / at Risk (%)	Affected / at Risk (%)
Total	16/24 (66.67%)	15/21 (71.43%)
Blood and lymphatic system disorders
Anaemia ^† 1	0/24 (0.00%)	1/21 (4.76%)
Cardiac disorders
Ascites ^† 1	0/24 (0.00%)	3/21 (14.29%)
Gastrointestinal disorders
Abdominal distension ^† 1	0/24 (0.00%)	1/21 (4.76%)
Abdominal pain ^† 1	1/24 (4.17%)	0/21 (0.00%)
Diarrhoea ^† 1	0/24 (0.00%)	3/21 (14.29%)
Pancreatitis ^† 1	2/24 (8.33%)	0/21 (0.00%)
General disorders
Multiple conditions defined for single event ^† 1	0/24 (0.00%)	1/21 (4.76%)
Injury, poisoning and procedural complications
Alcohol poisoning ^† 1	3/24 (12.50%)	0/21 (0.00%)
Investigations
Lipase increased ^† 1	1/24 (4.17%)	0/21 (0.00%)
Metabolism and nutrition disorders
Alcohol intolerance ^† 1	0/24 (0.00%)	3/21 (14.29%)
Psychiatric disorders
Anxiety ^† 1	1/24 (4.17%)	0/21 (0.00%)
Drug dependence ^† 1	1/24 (4.17%)	0/21 (0.00%)
Insomnia ^† 1	1/24 (4.17%)	0/21 (0.00%)
Renal and urinary disorders
Urinary tract infection ^† 1	0/24 (0.00%)	1/21 (4.76%)
Reproductive system and breast disorders
Erectile dysfunction ^† 1	1/24 (4.17%)	0/21 (0.00%)
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	1/24 (4.17%)	0/21 (0.00%)
Lung infection ^† 1	2/24 (8.33%)	0/21 (0.00%)
Pleural effusion ^† 1	0/24 (0.00%)	1/21 (4.76%)
Skin and subcutaneous tissue disorders
Pruritus ^† 1	1/24 (4.17%)	0/21 (0.00%)
Rash ^† 1	0/24 (0.00%)	1/21 (4.76%)
Skin infection ^† 1	1/24 (4.17%)	0/21 (0.00%)
1 Term from vocabulary, MedDRA Version 20.1 † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Mack C. Mitchell, MD
Organization:	U.T. Southwestern Medical Center
Phone:	2146485036
EMail:	mack.mitchell@utsouthwestern.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Vatsalya 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.

Layout table for additonal information

Responsible Party:	Mack Mitchell, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:	NCT01922895
Other Study ID Numbers:	STU 092012-012 U01AA021893-01 ( U.S. NIH Grant/Contract )
First Submitted:	August 12, 2013
First Posted:	August 14, 2013
Results First Submitted:	January 9, 2022
Results First Posted:	March 2, 2022
Last Update Posted:	March 2, 2022

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