Conditions: Acute Alcoholic Hepatitis
Keywords: Alcoholic Hepatitis MELD < 20 Probiotic Nutritional Supplement Lactobacillus Rhamnosus GG
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 45
Healthy volunteers: no

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.

Arms:
arm 1: Placebo capsule that matches the probiotic capsule in appearance will be given once daily for 180 days. arm 2: Dietary supplement capsule (Lactobacillus Rhamnosus GG) will be given once daily for 180 days.

Interventions: intervention 1: Lactobacillus Rhamnosus GG intervention 2: Placebo for Probiotic
Intervention descriptions: intervention 1: Probiotic nutritional supplement; Lactobacillus Rhamnosus GG intervention 2: Capsule manufactured without active ingredients.

Protocol document:
Prot_SAP_000.pdf: 
Official title: Novel Therapies in Moderately Severe Acute Alcoholic 
Hepatitis 
 
 
 
NCT number: NCT01922895 
IRB Approved date: November 16, 2015 


Page 1 of 16 
 
The University of Texas Southwestern Medical Center at Dallas 
Institutional Review Board 
Novel Therapies in Moderately Severe Acute Alcoholic Hepatitis 
1. Study Specific Aims: 
Aim 1: Evaluate the effects of probiotic supplements on improvement in MELD score and gut 
mucosal integrity in patients with MELD < 20. Patients will be randomized to receive daily probiotics 
(Culturelle®: a nutritional supplement containing Lactobacillus Rhamnosus GG, manufactured by 
iHealth, Inc.) for 6 months and standard of care treatment or placebo with standard care (described 
below). Primary outcome will be change in MELD score at 30 days after randomization. Secondary 
outcomes will be measured at 30, 90 and 180 days. These include improvement in MELD score, gut 
mucosal permeability, liver enzymes, serum endotoxin and the levels of TNF and other cytokines 
from baseline; and mortality. 
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 
all studies related to acute alcoholic hepatitis. Our research group will use the samples and share 
with others for future studies on biomarkers for AAH severity/outcome, cost analysis, rationales for 
new therapies, etc. 
2. Background: 
Acute alcoholic hepatitis (AAH) is an important cause of morbidity, mortality and healthcare costs in 
the United States and most Western countries. The 2007 nationwide inpatient sample from the 
Healthcare Cost and Utilization Project reported that 56,809 patients (0.71% of the total) were 
hospitalized with AH
(1). Average hospital costs were $37,769, more than twice the cost of myocardial 
infarction. Length of stay was significantly higher in those who died compared to those who survived 
(9.3 vs. 6.2 days). Total charges (~$85,000) were 2.5-fold higher in those who died than those who 
survived. The 28-day mortality of AAH in Denmark rose from 12 to 15%, and the 84-day mortality 
increased from 14 to 24% between 1999-2008
(2) with 5-year mortality of 56%. These data from 
Denmark are similar to the 1991 VA Cooperative data: 4-year mortality of 42% with AH alone, and 
65% with AH plus cirrhosis
(3). Aggregated mortality of 661 placebo-treated patients from 19 trials 
was 20% at 30 days and 34% at a median of 160 days follow-up
(4). 
Statistics illustrate the grim outcome of AAH despite major advances in critical care and other 
medical interventions over the last 3 decades. While hepatic steatosis develops in the majority of 
heavy drinkers, alcoholic hepatitis and cirrhosis occur in only 20-25% (reviewed in (5)). All patients 
with AAH have a background of hepatic steatosis that represents a consequence of metabolic and 
oxidative stress. The inflammatory nature of alcoholic hepatitis is highlighted clinically by elevation in 
white blood cell count (WBC) and occasionally fever and pathologically by infiltration of the liver with 
neutrophils. A number of studies have implicated the gut flora, in particular gut-derived toxins, as a 
“second hit” in the pathogenesis of acute alcoholic hepatitis and cirrhosis. Endotoxin 
(lipopolysaccharide, LPS) binds to toll-like receptor 4 (TLR4), a receptor that plays a key role in 
initiating release of tumor necrosis factor (TNFα) and other cytokines by activated Kupffer cells in 
experimental models of alcoholic liver injury
(6-8). 


Page 2 of 16 
 
High serum levels of TNFα are associated with the clinical severity of alcoholic hepatitis
(9) and there 
is increased production of TNFα in monocytes isolated from patients with alcoholic hepatitis
(10). Other 
studies have suggested that alcohol increases gut permeability in animal models and in heavy 
drinkers
(11), a potential contributing factor in how endotoxin or other bacterial products reach the liver. 
Endotoxemia occurs frequently in patients with cirrhosis and in those with chronic hepatitis
(12, 13) 
probably due to increased gut bacterial translocation. Furthermore, recent studies reported 
alterations in the gut microbiome in alcohol-fed animals
(14), a finding that could also promote 
increased permeability of the gut mucosa. We hypothesize that impairment of gut mucosal 
integrity is the unifying “second hit” with potential contributing factors including the 
microbiome, nutritional deficiencies and direct effects of alcohol. 
Published data show that several agents are beneficial in short-term treatment of severe AAH, but 
none has proven to impact 6 month mortality when used as monotherapy
(15). Combining therapeutic 
agents that target different pathways while avoiding the risks of infection and hepatorenal syndrome 
may improve mortality particularly in the most severely ill patients with AAH. Furthermore, no 
specific interventions or medications benefit patients with mild to moderate AAH
(14). The proposed 
study will use specific agents to target impairment in gut mucosal integrity in patients with 
moderately severe AAH. The potential benefit is to not only to improve treatment but also to provide 
evidence of the roles of gut mucosal integrity in the pathogenesis of AAH. 
The proposed studies represent the culmination of a planning process involving the members of the 
proposed Executive Committee and other co-investigators. The criteria for selecting the proposed 
treatment included a known safety profile so that a beneficial treatment(s) could be brought forward 
for a phase III clinical trial and/or transform treatment for AAH, a condition for which the current 
treatment paradigm is unsatisfactory. The selection of the medications was based on the 
hypothesis that the syndrome of AAH results from inflammation triggered by gut derived 
endotoxins and other bacterial products as a consequence of increased permeability of the 
gut mucosa. 
The standard of care (nutritional support, alcohol abstinence and counseling) is recommended by 
both the American Association for the Study of Liver Diseases and the American College of 
Gastroenterology in published practice guidelines
(5, 16) [PMID 20034030, PMID 9820369]. 
3. Concise Summary of the Project: 
Our studies will test the hypothesis that the syndrome of acute alcoholic hepatitis (AAH) results from 
severe inflammation and dysregulated cytokines, providing the “second hit” that causes an acute 
deterioration. We further hypothesize that gut derived endotoxins and other bacterial products trigger 
inflammation and are a consequence of increased permeability with altered gut barrier function. 
We will utilize published models for predicting mortality in patients with AAH to stratify patients 
based on severity. Although previous studies of treatment for severe AAH utilized 30-day mortality 
as an endpoint, 6-month mortality is a more relevant outcome, in part because most transplantation 
programs require 6 months of abstinence before active listing. Furthermore, the number of deaths 
between 6 and12 months in abstinent patients is low compared to the number in the first 6 months. 
Patients will be stratified into those with Model of End-stage Liver Disease (MELD) score < 20 and 
MELD > 20. Those stratified into the severe group are described in a separate application. The 
primary difference between the Maddrey discriminant function (DF) and the MELD is that the latter 
includes creatinine. We propose to use the MELD score to stratify for severity. 
 


Page 3 of 16 
 
 
Specific Aim 1 = Randomized controlled trial for moderate alcoholic hepatitis: MELD < 20: 
Patients with moderate AAH will be randomized to receive either standard of care plus placebo or 
standard of care plus probiotic capsules in a 1:1 ratio. 
The primary outcome will be 30-day change in MELD score from baseline. Secondary 
outcomes will be change in MELD score from baseline at 90 and 180 days and changes from 
baseline in the gut mucosal integrity as assessed by the lactulose/mannitol test. Changes in serum 
endotoxin levels and cytokine profiles including TNFα will also be measured as secondary outcomes. 
We predict that probiotics will stabilize gut-barrier function, decrease endotoxemia, 
accelerate improvement in liver enzymes, and may slow or prevent progression of liver 
disease. 
Specific Aim 2 = Natural history of moderately severe acute alcoholic hepatitis: MELD < 20: 
Patients with moderately severe AAH/alcoholic liver disease who decline to be randomized but 
consent to prospective data collection and minimal risk non-invasive studies (blood drawing and 
urine collection) 
Specific Aim 3 = Subjects will be asked for a DNA blood draw during the first day of the study 
All human subjects will be patients with a clinical presentation consistent with acute alcoholic 
hepatitis (AAH). The trial is designed to test the hypothesis that AAH results from inflammation 
triggered by gut derived endotoxins and other bacterial products as a consequence of increased 
permeability of the gut mucosa. Patients with AAH will be stratified by disease severity as 
determined by the Model for End-Stage Liver Disease (MELD) score and enrolled in one of two 
randomized controlled trials. 
Subject population: The total subject population will be 260 patients with alcoholic hepatitis, 130 in 
each disease severity group (moderate disease is defined as MELD < 21 and severe disease as 
MELD 21 – 31 and MELD > 31). The age range will be 21 – 70 years old. The health status of the 
population will be that of a group with significant acute clinical presentation from alcoholic liver 


Page 4 of 16 
 
disease. 
Sampling plan: The sample size was calculated based on the analysis of patients with alcoholic 
liver disease in the (SRTR) database, accounting for drop-out, lost-to-follow-up and non-evaluable 
results and including a factor for possible non-representativeness of the original database. In 
addition, preliminary data for 114 patients meeting criteria were used in the calculations and 
stratification decisions. 
 
4. Criteria for Inclusion of Subjects: 
a) Ability to provide informed consent by subject or appropriate family member 
b) Age between 21-70 years 
c) Recent alcohol consumption > 50 g/d for > 6 months, continuing within two months before 
enrollment 
d) At least 2 of the following symptoms or signs of acute alcoholic hepatitis: Anorexia, nausea, 
RUQ pain, jaundice, leukocytosis, hepatomegaly AND 
e) Elevation of AST ≥ 50 U/L, but < 500 U/L; AST > ALT and ALT < 200 U/L; total bilirubin > 3 
mg/dL AND 
f) 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):  
g) Model for End-Stage Liver Disease (MELD) <20 
 
5. Criteria for Exclusion of Subjects: 
a) Hypotension with BP < 80/50 after volume repletion 
b) Pregnancy; incarceration; inability to provide consent or lack of appropriate family member 
c) Signs of systemic infection: Fever > 38
o C and positive blood or ascites cultures on 
appropriate antibiotic therapy for > 3 days within 3 days of inclusion 
d) Acute gastrointestinal bleeding requiring > 2 units blood transfusion within the previous 4 
days 
e) 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 
f) Previous treatment with corticosteroids or other immunosuppressive medications including 
specific anti-TNF therapy (not including pentoxifylline), calcineurin inhibitors within the 
previous 3 months 
g) Evidence of acute pancreatitis: CT evidence or amylase or lipase > 4 X ULN 
h) Serious cardiac, respiratory or neurologic disease or evidence of autoimmune hepatitis, 
primary biliary cirrhosis, primary sclerosing cholangitis, Wilson disease, hemochromatosis, 
secondary ion overload due to chronic hemolysis, alpha-1-antitrypsin deficiency 
6. Study Procedures: 
Aim 1 
Patients will be screened, stratified as moderate or severe acute alcoholic hepatitis and randomized 
to one of two arms for the clinical trial. Randomization will be in blocks of 6 using a sealed, opaque 
envelope. The study procedures are tabulated and divided into standard of care (“Standard”) and 
research-specific (“Research”) studies. Between days 2 and 7, between days 8 and 27, at 2 months, 
4 months and 5 months follow-up, clinically indicated standard studies will be obtained. Study 


Page 5 of 16 
 
procedures are described in the table. 
 
Study Procedures by Study Day: 
A summary of evaluations is located in the schedule of events table provided at the end of this 
section. The procedures and evaluations are outlined below. 
 
Screening: 
Complete screening for eligibility will occur once the informed consent has been obtained as 
described above. Patients will be evaluated on the basis of clinical and laboratory data during pre-
screening and stratified into moderate or severe alcoholic hepatitis. Patients will be evaluated for 
entry into the study according to the stated inclusion and exclusion criteria. Individuals who are 
identified during screening as not eligible for the study need not complete all screening procedures 
but will be provided the option to enroll in the natural history study. The reason for ineligible status 
will be documented on the Screen Failure Log. 
 
The following procedures will be obtained or performed to evaluate each patient’s general health 
and qualifications for participation in the study: 
 
Signed, written informed consent 
 
Demographic information including gender, date of birth, race and ethnicity. 
 
Medication history over the past 30 days, including prescription and non-prescription  over-
the-counter medications, herbal medications, vitamins and minerals. 
 
Alcohol usage in the past 60 days prior to assessment specifically and the pattern of  chronic 
usage. 
 
Review inclusion and exclusion criteria 
 
Collection of blood for hematology, coagulation, clinical chemistry to include amylase  and 
lipase, ammonia, and in female patients, a pregnancy test. 
 
Physical examination, including height, weight (body mass index will be calculated  based on 
these variables), and vital signs (systolic and diastolic blood pressure, pulse   rate, 
respiratory rate and body temperature) 
 
Ultrasound of the belly if no x-rays already obtained. This is standard of care in patients  
hospitalized with alcoholic hepatitis.   
 
Assessments at baseline and during study treatment:   
Study day 0 – baseline (within 24 hours of study enrollment) 
 
Complete collection of all baseline history. Review of alcohol use history using the  validated 
timeline 
followback 
method. 
Forms 
http://www.nova.edu/gsc/online_files.html 
 
(http://pubs.niaaa.nih.gov/publications/AssessingAlcohol/InstrumentPDFs/13_TLFB.pdf) 
 
Complete collection of all indicated standard of care laboratory evaluations (chemistry,  
hematology, coagulation, urine, microbiology, viral, and TB testing). 
 
Ascites evaluation, if present. 
 
Collection of baseline research testing to include urine, blood, DNA and stool testing. 
 
Collect prior and concomitant medications. 
 
Clinical assessment to include vital signs and physical exam details. 
 
Nutritional assessment with a hand grip dynamometer  
 
Treatment day 1 – time zero (alternatively note this as treatment day one with no time and above as 
study day 1 baseline) 
 
Begin continuous AE review and reporting 
 
Begin once daily dosing of oral study medication or placebo preparation. 
 


Page 6 of 16 
 
Treatment day 2: 
 
Inpatient assessment to include: 
 
Review baseline history for changes. Review alcohol intake history. 
 
Collection of prior and concomitant medications 
 
Clinical assessment including vital signs and physical exam details 
 
Collection of blood for clinically indicated laboratory studies. 
 
Collection of research laboratory studies including urine and blood. 
 
Complete 24 hour urine collection. 
 
Continue once daily dosing of oral study medication or placebo preparation. 
 
Continuous AE review and reporting.  
 
Treatment days 3-6: 
 
If patient remains inpatient or has clinically indicated outpatient visit: 
 
Review baseline history for changes. Review alcohol intake history. 
 
Collection of prior and concomitant medications 
 
Clinical assessment including vital signs and physical exam details 
 
Collection of blood for clinically indicated laboratory studies. 
 
Continue once daily dosing of oral study medication or placebo preparation. 
 
Continuous AE review and reporting.  
 
Treatment day 7 ± 2 days: 
 
Inpatient assessment or required outpatient clinic visit to include: 
 
Review baseline history for changes. Review alcohol intake history. 
 
Collection of prior and concomitant medications 
 
Clinical assessment including vital signs and physical exam details 
 
Collection of blood for clinically indicated laboratory studies. 
 
Collection of research laboratory studies including urine and blood. 
 
Continue once daily dosing of oral study medication or placebo preparation. 
 
Continuous AE review and reporting.  
 
Treatment days 8-14: 
 
If patient remains inpatient or has clinically indicated outpatient visit: 
 
Review baseline history for changes. Review alcohol intake history. 
 
Collection of prior and concomitant medications 
 
Clinical assessment including vital signs and physical exam details 
 
Collection of blood for clinically indicated laboratory studies. 
 
Continue once daily dosing of oral study medication or placebo preparation. 
 
Continuous AE review and reporting.  
 
Treatment days 15-27: 
 
If patient remains inpatient or has a clinically indicated outpatient visit: 
 
Review baseline history for changes. Review alcohol intake history. 
 
Collection of prior and concomitant medications 
 
Clinical assessment including vital signs and physical exam details 
 
Collection of blood for clinically indicated laboratory studies. 
 
Continue once daily dosing of oral study medication or placebo preparation.  
 
Continuous AE review and reporting. 
Treatment day 28 ± 2 days: 
 
Inpatient assessment or required outpatient clinic visit to include: 
 
Review baseline history for changes. Review alcohol intake history. 
 
Collection of prior and concomitant medications 
 
Clinical assessment including vital signs and physical exam details 


Page 7 of 16 
 
 
Collection of blood for clinically indicated laboratory studies. 
 
Collection of research laboratory studies including urine and blood. 
 
Continue once daily dosing of oral study medication or placebo preparation. 
 
Continuous AE review and reporting.  
 
Treatment day 29 to 2 months: 
 
Continue once daily dosing of oral study drug or placebo preparation. 
 
Continuous AE review and reporting. 
 
If patient remains inpatient during this interval or completes clinically indicated outpatient visit 
during this time, the following data will be recorded: 
 
Review baseline history for changes. Review alcohol intake history. 
 
Collection of prior and concomitant medications 
 
Clinical assessment including vital signs and physical exam details 
 
Collection of blood for clinically indicated laboratory studies.  
 
Treatment 3 months ± 2 weeks: 
 
Inpatient assessment or required outpatient clinic visit (noted as 3 mos on schedule of 
events table) to include: 
 
Review baseline history for changes. Review alcohol intake history. 
 
Collection of prior and concomitant medications 
 
Clinical assessment including vital signs and physical exam details 
 
Collection of blood for clinically indicated laboratory studies. 
 
Collection of research laboratory studies including urine and blood. 
 
Continue once daily dosing of oral study drug or oral placebo preparation 
 
Collection of research laboratory studies including urine and serum 
 
Continuous AE review and reporting.  
 
Treatment 4, 5 months ± 2 weeks: 
 
Continue once daily dosing of oral study drug or oral placebo preparation 
 
Continuous AE review and reporting. 
 
If patient remains inpatient or completes clinically indicated outpatient visit during this time, 
the following data will be collected and recorded at the closest interval month: 
 
Review baseline history for changes. Review alcohol intake history. 
 
Collection of prior and concomitant medications 
 
Clinical assessment including vital signs and physical exam details 
 
Collection of blood for clinically indicated laboratory studies.  
 
Treatment 6 months ± 2 weeks: 
 
STOP all study and placebo medications. 
 
Complete abdominal ultrasound. 
 
Inpatient assessment or required outpatient clinic visit to include: 
 
 Review baseline history for changes. Review alcohol intake history. 
 
Collection of prior and concomitant medications 
 
Clinical assessment including vital signs and physical exam details 
 
Collection of blood for clinically indicated laboratory studies. 
 
Collection of research laboratory studies including urine, blood and stool. 
 
Continuous AE review and reporting. 
Follow up of early termination: 
A safety follow up visit will be performed approximately 30 days after discontinuation of study drug 
for all patients that discontinued without withdrawing informed consent. Evaluation will include: 
 
Collection of blood for standard of care labs to include chemistry, hematology and 
coagulation studies. 


Page 8 of 16 
 
 
Clinical assessment to include vital signs and physical exam details. 
 
Review baseline history for changes. Review alcohol intake history. 
 
Collection of concomitant medications. 
 
AE review and reporting. 
 
Review and recording of reason for early termination. 
 
 


Page 9 of 16 
 
Purpose 
Test 
Day 0  
Day  
2 – 6* 
Day 7 
Day  
8 – 27*  Day 28 
2  
mos *† 
3  
mos † 
4  
mos *† 
5  
mos *† 
6  
mos † 
Standard 
Clinical assessment  
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Alcohol intake 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Liver 
panel 
(bilirubin, 
alkaline 
phosphatase, AST, ALT) and GGT 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Serum electrolytes, creatinine, BUN 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Serum albumin, total protein 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Prothrombin time, INR 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Complete blood count 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Haptoglobin 
x 
 
 
 
 
 
 
 
 
x 
 
Lipid panel 
x 
 
 
 
 
 
 
 
 
x 
 
Amylase, lipase 
x 
 
 
 
 
 
 
 
 
 
 
HIV 
x 
 
 
 
 
 
 
 
 
 
 
HAV Ab, HBsAg, HBcore Ab (total)  
x 
 
 
 
 
 
 
 
 
 
 
HCV Ab 
x 
 
 
 
 
 
 
 
 
 
 
PPD 
x 
 
 
 
 
 
 
 
 
 
 
Blood cultures x2 
x 
 
 
 
 
 
 
 
 
 
 
Urine culture & urinalysis 
x 
 
 
 
 
 
 
 
 
 
 
24 hour urine  
(Na, K, creatinine, protein) 
x 
 
 
 
 
 
 
 
 
 
 
Urine toxicology 
x 
 
 
 
 
 
 
 
 
 
 
Ascites for albumin, total protein, cell 
count and differential (if present) 
x 
 
 
 
 
 
 
 
 
 
 
Ascites culture 
x 
 
 
 
 
 
 
 
 
 
 
Stool studies (if diarrhea): C. difficile, 
culture 
x 
 
 
 
 
 
 
 
 
 
 
CXR 
x 
 
 
 
 
 
 
 
 
 
 
Complete abdominal ultrasound or 
cross-sectional radiology 
x 
 
 
 
 
 
 
 
 
x 
Research 
Gut permeability studies 
x ‡ 
 
 
 
x 
 
x 
 
 
x 
 
Serum zinc, urine zinc 
x 
 
 
 
x 
 
 
 
 
x 
 
Stool (DNA microbiome) 
x 
 
 
 
 
 
 
 
 
x 
 
Urine (KIM-1) 
x 
x day2 
x 
 
x 
 
x 
 
 
x 
 
Biomarkers = Cytokines 
x 
x day2 
x 
 
x 
 
x 
 
 
x 
 
DNA = Pharmacogenomics 
x 
 
 
 
 
 
 
 
 
 
 
Serum micro RNA 
x 
 
x 
 
x 
 
x 
 
 
X 
 
Monocyte prep (U Mass, U Louisville) 
x 
 
x 
 
 
 
 
 
 
X 
Blood 
Research total volume = 179 mL 
45 
  
30 
  
37 
  
30 
  
  
37 
 
SOC total volume = 208 mL 
82 
14 
14 
14 
14 
14 
14 
14 
14 
14 
 
Combined = 387 mL = 26 tbspns 
117 
14 
44 
14 
51 
14 
44 
14 
14 
51 
* clinically indicated, † ± 2 weeks, ‡ within first 28 days  


Page 10 of 16 
 
Sub-Study Procedures: 
1. Optional Natural History (minimal risk with urine and blood collection): All screened subjects 
meeting inclusion and exclusion criteria below or declining consent to randomization will be 
invited to join this study of the natural history of severe acute alcoholic hepatitis. The natural 
history of patients with severe alcoholic hepatitis is not well documented in the current era. 
Prospective collection of data in parallel with the randomized study subjects has great 
potential value. Every patient who agrees and give consent will be seen in follow-up as 
clinically indicated. At each visit that coincides with collection of samples for research, or as 
close to Baseline, Day 7, Day 28, Month 3 and 6, the subjects will be offered the opportunity 
to participate. Patients may also be asked to participate in the natural history study as a one-
time draw at the day of consent.  
4.a. Criteria for Inclusion of Subjects for Natural History Specimen Collection: 
a. Ability to provide informed consent by subject or appropriate family member  
b. Age between 21-70  
c. Recent alcohol consumption > 50 g/d for > 6 months, continuing within six months before 
enrollment  AND/OR 
d. Suspected or proven alcoholic liver disease 
 
5. a. Criteria for Exclusion of Subjects for Natural History Specimen Collection:  
a. Pregnancy; incarceration; inability to provide consent or lack of appropriate family member  
b. Signs of uncontrolled systemic infection: Fever > 38o C; positive blood or ascites cultures on 
appropriate antibiotic therapy for >3 days within 3 days of inclusion  
c. Evidence of acute pancreatitis: CT evidence or amylase or lipase > 5 X ULN  
d. Evidence of other liver diseases such as autoimmune hepatitis, primary biliary cirrhosis, 
primary sclerosing cholangitis, Wilson disease, biopsy proven hemochromatosis, alpha-1-
antitrypsin deficiency 
 
Over the entire 6 months study period 387 mL of blood will be drawn, comprising 208 mL for 
standard of care tests and 89 mL for research studies. 
Optional DNA Blood Sample Collection: A biorepository can serve as a national resource for 
all studies related to acute alcoholic hepatitis. A major goal of the U-01 consortium is to 
share clinical samples. Our research group will use the samples and share with others for 
future studies on biomarkers for AAH severity/outcome, cost analysis, rationales for new 
therapies, etc. Blood and tissue samples will be collected as indicated in the table. Samples 
for DNA preparation will be shipped to the Cleveland Clinic and specimens will be shipped to 
those translational sites that are studying biomarkers or pharmacogenomics (U Mass, U 
Louisville). Specimens will only be identified by the unique study number. De-identified data 
obtained from the various pharmacogenomics, miRNA and transcriptosome screens will be 
placed on the website of the U-01 consortium and be available to the U-01 investigators 
throughout the study. 
The amount of blood that would be collected is 8 mL (2 tbspns) and it will be stored at the 
Cleveland Clinic Foundation as part of the NIH Tissue and Biorepository for Alcoholic 
Hepatitis Studies. 
 


Page 11 of 16 
 
7. Sources of Research Material:  
Specimens: Blood, urine, stool 
Blood for research purposes will be collected at the same time as blood for clinical care. Urine 
specimens will be collected either with clinical care samples or at special research visits during 
follow-up after discharge. All samples will only be identified using a unique study number and 
processed as necessary for local storage or shipping to central testing sites. 
Stool samples will be collected by giving a collection kit to the subjects. 
A unique study number will be assigned to each subject. The unique study number will be assigned 
centrally at the time of randomization and used to code all samples. The study site will be identified 
by the first digit (1 – 4), the subject by the last 3 digits and the disease stratification by the total 
number of digits (4 for moderate alcoholic hepatitis). This procedure allows any site to exceed 100 
subjects enrolled in either study. 
 
Data: Any past medical history, family history, social history (including dietary and occupational 
history), medications and other ingested supplements potentially related to etiology or complications 
of liver disease and alcohol consumption not provided in the electronic medical records. 
 
Electronic medical record: Data pertaining to current hospitalization, past medical history, family 
history, social history (including dietary and occupational history), medications and other ingested 
supplements potentially related to etiology or complications of liver disease and alcohol 
consumption; physical examination. 
Standard of care laboratory investigations: Results of routine blood chemistry tests = blood 
electrolytes, renal and liver function tests, pancreas enzymes, lipid panel, urine and fluid chemistry; 
hematology = complete blood count, coagulation and hemolysis studies, fluid cell counts; infectious 
diseases = viral hepatitis serologies, tests for HIV and tuberculosis; blood, urine and fluid cultures; 
stool culture and toxins. Results of routine radiology = chest x-ray, complete abdominal ultrasound. 
Data from the results of research studies: gut permeability, blood and urine zinc, blood DNA 
(genomics) and stool DNA (microbiome), blood micro RNA, blood and urine inflammation 
biomarkers, blood mononuclear cells responses. A measure of nutritional status will be obtained via 
a hand grip measurement with the JAMAR dynamometer.   
A list of study patients will be maintained in the electronic medical record at each site and in no other 
place. The list will be assigned to one investigator at each site. Access to the list, within the 
electronic medical record, will be granted to the other investigators and research nurses at the study 
site. The security of the electronic medical record will provide full protection to any individually 
identifiable private information. 
8. Recruitment Methods and Consenting Process: 
Potential patients will be identified from daily results of routine chemistry tests (bilirubin > 3 mg/dL, 
AST > ALT and > 1.5x upper limit of normal but < 500 U/L) and screened for inclusion and exclusion 
criteria. The primary physicians will be approached for permission to meet the patient and will 
introduce the researchers. 
The potential subject will be introduced to the researcher(s) by provider(s) on the healthcare team 
responsible for the hospitalization (inpatients) or encounter (Emergency Department or outpatient). 
The study will be discussed in detail, with a translator as needed, and the consent form explained. 


Page 12 of 16 
 
Subjects will be given a copy of the consent form to keep, with a Spanish fully translated version as 
needed. When they have made a decision, the consent will be signed and witnessed if they are 
agreeable to participating. The time frame is 7 days from initial identification as eligible until study 
enrollment. 
Circumstances for consent: Subjects will be approached by one of the physician investigators, in a 
confidential environment with family members present if desired. The information provided will be all 
that data in the IRB-approved consent form, using interpretation service as needed via hospital 
language lines. The consent document, in English or Spanish, will be given to the subject as 
described above. After agreement to participate, the form will be signed and witnessed; a complete 
copy of the entire document will be provided to the subject in English or Spanish as required. 
If the subject’s condition is considered mentally unable to provide informed consent by the primary 
management team then a legal representative will have the option to sign the consent form until 
such time as the subject regains capacity. One of the complications of severe alcoholic hepatitis is 
hepatic encephalopathy. If this complication is diagnosed clinically, then the legal representative will 
be required to sign the consent form until the encephalopathy has resolved. It is much less likely to 
occur in moderate alcoholic hepatitis. 
 
 
9. Potential Risks: 
Physical risks: 
Probiotics are bacteria normally found in the gastrointestinal tract. They are deliberately cultured in 
yogurts and are a nutritional supplement. 
Side effects 
Frequent 
>20% of subjects 
Occasional 
2 - 20% of subjects 
Rare 
Less than 2% of subjects 
Serious 
 
 
Infection with probiotic bacteria 
(1 adult) 
Less Serious 
 
 
 
Minor 
 
Burping Hiccups 
 
 
10. Subject Safety and Data Monitoring: 
Data Safety Monitoring Board (DSMB): The DSMB will consist of three experienced clinicians to 
exercise oversight of the safety of trial participants. It will be chaired by Dr. Willis Maddrey 
(Professor of Internal Medicine, UT Southwestern Medical Center), review periodic safety reports 
prepared by the trial biostatistician (Dr. Bruce Barton), request additional data/information (if 
necessary), and advise the trial Executive Committee regarding continuation/discontinuation of the 
study. 
The External Medical Safety Monitor (EMSM, Dr. Maddrey) will closely monitor the incidence rates 
of all adverse events reported, whether serious or not, throughout the study, and will alert the DSMB 
if a trend is observed. A summary of all AEs and SAEs, a summary of all reports, and a coded list of 
all subjects who were terminated from the study due to study-related adverse events, will be 
included in reports submitted by the DMSB to the IRBs. An annual report will be submitted to the 
IRBs at all participating sites. 


Page 13 of 16 
 
Clinical performance sites will report all fatal events, unanticipated problems and other serious 
adverse events and suspected adverse reactions to the Data Safety Monitoring Board (DSMB) and 
IRB by secure email within 24 hours of first knowledge of the event. Additionally, all current 
study data for that particular subject will be entered to allow for timely review by the EMSM, Dr. 
Willis Maddrey. 
11. Procedures to Maintain Confidentiality: 
Any time information is collected; there is a potential risk for loss of confidentiality. Every effort will 
be made to keep information confidential; however, this cannot be guaranteed. 
Privacy of individuals: The privacy of individuals will be protected by using confidential surroundings 
for all communications, eliciting and honoring requests for the inclusion and exclusion of family 
members and partners and following the institutions’ codes for ethical and professional conduct of 
research and patient-centered care. 
Confidentiality of data: No personally identifiable information will be recorded outside the electronic 
medical record. Only those individuals with rights to access the patient’s electronic medical record 
will know the identity of the study subjects. While no efforts at security are completely free of risk, 
this approach is such that the risk of accidental exposure is negligible. 
 
12. Potential Benefits: 
The potential benefits to every subject participating in the clinical trial are related to receiving optimal 
patient-centered care for their condition. This includes ensuring the mobilization of available 
resources for rehabilitation programs and the education of all involved patients and their families on 
the possible consequences of alcohol consumption, particularly in high risk sub- populations. While 
ideally occurring in the care of all patients with alcoholic hepatitis, the study team will provide 
patients with the personal healthcare navigation assistance that is not available to every individual. 
There may be immediate additional benefits to those in the active study arms if the outcomes are 
favorable. If the outcomes are favorable, all patients with severe alcoholic hepatitis may benefit from 
extrapolation of the findings. If the outcomes are negative, other subjects will be protected from the 
risks of treatment that has no additional benefit to convey. 
There is a potential societal benefit in the general outcomes of the clinical trial with respect to 
alcohol consumption, alcoholism and alcoholic liver disease. In addition, the potential financial 
benefits of a successful program are substantial. 
13. Biostatistics: 
Sample size for study of patients with moderate acute alcoholic hepatitis 
To compare change from baseline in the two groups of moderate AAH patients, we find that a two-
sided twosample t-test of change in MELD score from baseline (mean=17.0) to 30 days with an 
overall sample size of 108 patients (54 in each treatment group) achieves 80% power with an alpha 
level of 0.05 to detect a difference in mean change of MELD score of 5.0 in the control group 
compared to a mean change of 8.0 in the intervention (probiotic) group with a common estimated 
group MELD score standard deviation of 5.559. 
Adjusting for a total of 20% withdrawal, lost to follow-up or non-evaluable, we have n* = 108/ (1- 


Page 14 of 16 
 
0.20) = 108/.80 = 136 patients total or 68 patients in each treatment group. We expect that, in a 
multivariate model, we will have the power to detect smaller treatment group differences due to the 
partition of the variance among the predictors. 
Statistical analysis plan: Our primary analysis of change in MELD score from baseline to 30 days 
will be an unadjusted comparison of change (Day 30 – Baseline) using a standard two- group t-test 
at a two-sided alpha level of 0.05 with appropriate adjustment for unequal variances. We will also 
conduct secondary analyses to further investigate factors that influence the change as well as adjust 
for any imbalances in patient characteristics and covariates between treatment groups. Our initial 
model will be an Analysis of Covariance (ANCOVA) model with change in MELD score as the 
outcome and with treatment group (0=control, 1=probiotic) and baseline MELD score as predictors. 
Additional models will include patient characteristics such as age, gender, time since diagnosis as 
well as other covariates such as ALT, AST, and other laboratory measures at baseline. Finally, as it 
is likely that MELD score can be calculated throughout the duration of the study, we will use mixed 
models to analyze the longitudinal MELD score data. Mixed (random effects) models are used to 
adjust for the inherent correlation among the laboratory (and, thus, MELD score) measures on the 
same patient. We will consider treatment as a fixed effect, but most other factors as random effects. 
The model will also include a time metric, so that, rather than the change from baseline, we can use 
the coefficients of the times as estimates of the change from baseline (time=0), adjusted for the 
other factors in the model. So, for example, if MELD score is calculated at Days 0, 7, 14, 21, and 30, 
the model might look like: MELDt = β0 + β1*tx + β2*gender + β3*age + β4*Day7 + β5*Day14 + 
β6*Day21 + β7*Day30 where MELDt = MELD score at time t (t=0,7,14,21,30), β0...β7 = regression 
coefficients, tx = treatment (0=control, 1=probiotic), gender = patient’s gender (0=female, 1=male), 
age=patient’s age at last birthday, Day7 = MELD score at Day 7 (0=No, 1=Yes), ..., Day30 = MELD 
score at Day 30 (0=No, 1=Yes). This implies that the baseline MELD score is represented by 
Day7=Day14=Day21=Day30=0. Interpreting this model, which makes maximum use of all available 
MELD scores, the coefficient β4 is the estimate of the change in MELD score from baseline to Day 7, 
β5 is the estimate of the change in MELD score from baseline to Day 14, etc. By combining all of the 
information into a single model, we can adjust the MELD score changes for other factors as well as 
test for a difference in the slopes of the changes between the two treatment groups. The model can, 
of course, be extended beyond 30 days if measures are available. The fit of the model will be 
assessed primarily through the likelihood ratio test of the fitted model to the intercept only model. All 
coefficients will be tested for significance at a critical level of p=0.05. 
Sample size for study of patients with severe acute alcoholic hepatitis 
Using the Lakatos approach
(17) to estimating the sample size for a log-rank test, we find that a two-
sided logrank test with an overall sample size of 130 patients (65 patients each of the control and 
treatment groups) achieves 80.0% power at a 0.05 significance level to detect a hazard ratio of 
0.4447 when the proportion surviving at 6 months in the control group is 0.64 and 0.82 in the 
treatment group. The total study duration is 2.5 years of which subject accrual (entry) occurs in the 
first 2 years. We assume that the accrual pattern is uniform throughout the accrual period and that 
the proportion drop-out in each group is 0.10 during the 6 months with no treatment cross-overs. As 
a sensitivity analysis of these estimates, we used the Lachin- Foulkes approach
(18), a slightly less 
flexible approach and, with the same assumptions as above, we estimate 53 patients in each group, 
reasonably close to the Lakatos estimates. Thus, to be conservative in our estimates, we will set our 
sample size as 130 patients total or 65 patients in each treatment group. PASS II (NCSS, Kaysville, 
Utah) was used for all sample size calculations
(19). 
Statistical analysis plan: Our primary analysis of this outcome will be the unadjusted log-rank test 
of the Kaplan-Meier survival estimates for the two treatment groups at a two-sided alpha level of 
0.05 with survival censored at 6 months. Secondary analysis will use a Cox proportional hazards 


Page 15 of 16 
 
regression model (with survival censored at 6 months) to adjust the treatment difference in survival 
for patient characteristics (e.g., age, gender, time since diagnosis) and other covariates (e.g., ALT, 
AST, other lab measures). Predictors will be added to the model using reference cell coding, as with 
the mixed models above. The Cox model generates estimates of the hazard ratio for each factor 
compared to the reference level; e.g., for male patients vs. female patients, assuming gender = 1 for 
male and 0 for females, a hazard ratio of 1.25 indicates that males have a 25% higher probability of 
death overall by 6 months compared to females. We can also add time-dependent covariates to the 
model, such as ALT levels at 2 and 4 months, to estimate their predictive value for mortality. To 
assess the fit of the model, we will use Nagelkerke’s R2 constructed from the ratio of the likelihoods 
for the fitted model to the intercept only model. As further secondary analysis, we can eliminate the 
survival censoring at 6 months and test the overall survival throughout the duration of follow-up. 
General analysis plan for experiments with fold change as the outcome: Initial analyses will be 
descriptive in nature, allowing for investigation of appropriate normalization approaches. Initial 
comparative analyses of fold-change between treatment groups (or between other groups of 
interest) will be through a standard two-group t-test at the p=0.05 level with appropriate adjustment 
for unequal variances. If the fold change data are longitudinal in nature, we will use mixed (random 
effects) models to estimate the change in fold-change over time. In these models, fold-change at 
each time point will be the outcome with treatment (or other group indicator) and time as predictors. 
Additional patient characteristics can be added to the model to create adjusted estimates of 
treatment (or other group) differences. Mixed models can adjust for the correlation due to measures 
within patients and due to repeated microarrays at each time point. 
References 
1. 
Liangpunsakul S. Clinical Characteristics and Mortality of Hospitalized Alcoholic Hepatitis 
Patients in the United States. J Clin Gastroenterol. 2011;45(8):714-9.  
2. 
Sandahl TD, Jepsen P, Thomsen KL, Vilstrup H. Incidence and mortality of alcoholic 
hepatitis in Denmark 1999-2008: a nationwide population based cohort study. J Hepatol. 
2011;54(4):760-4. Epub 2010/12/04. 
3. 
Chedid A, Mendenhall C, Gartside P, French S, Chen T, Rabin L. Prognostic factors in 
alcoholic liver disease. VA Cooperative Study Group. Am J Gastroenterol. 1991;86(Feb(2)):210-6. 
4. 
Yu C-H. Early mortality of alcoholic hepatitis: A review of data from placebo-controlled clinical 
trials. World Journal of Gastroenterology. 2010;16(19):2435. 
5. 
O'Shea RS, Dasarathy S, McCullough AJ. Alcoholic liver disease. Hepatology. 
2010;51(1):307- 28. 
6. 
Yin M, Wheeler MD, Kono H, Bradford BU, Gallucci RM, Luster MI, et al. Essential role of 
tumor necrosis factor alpha in alcohol-induced liver injury in mice. Gastroenterology. 
1999;117(4):942-52. Epub 1999/09/29. 
7. 
Uesugi T, Froh M, Arteel GE, Bradford BU, Thurman RG. Toll-like receptor 4 is involved in 
the mechanism of early alcohol-induced liver injury in mice. Hepatology. 2001;34(1):101-8. Epub 
2001/06/30.  
8. 
Gao B, Seki E, Brenner DA, Friedman S, Cohen JI, Nagy L, et al. Innate immunity in 
alcoholic liver disease. Am J Physiol Gastrointest Liver Physiol. 2011;300(4):G516-25. Epub 
2011/01/22. 
9. 
Felver ME, Mezey E, McGuire M, Mitchell MC, Herlong HF, Veech GA, et al. Plasma tumor 
necrosis factor alpha predicts decreased long-term survival in severe alcoholic hepatitis. Alcohol Clin 
Exp Res. 1990;14(2):255-9. Epub 1990/04/01. 
10. 
Gobejishvili L, Barve S, Joshi-Barve S, McClain C. Enhanced PDE4B expression augments 
LPS- inducible TNF expression in ethanol-primed monocytes: relevance to alcoholic liver disease. 
Am J Physiol Gastrointest Liver Physiol. 2008;295(4):G718-24. Epub 2008/08/09. 
11. 
Szabo G, Bala S. Alcoholic liver disease and the gut-liver axis. World J Gastroenterol. 
2010;16(11):1321-9. Epub 2010/03/20. 


Page 16 of 16 
 
12. 
Fukui H, Brauner B, Bode JC, Bode C. Plasma endotoxin concentrations in patients with 
alcoholic and non-alcoholic liver disease: reevaluation with an improved chromogenic assay. J 
Hepatol. 1991;12(2):162-9. Epub 1991/03/01. 
13. 
Lin RS, Lee FY, Lee SD, Tsai YT, Lin HC, Lu RH, et al. Endotoxemia in patients with chronic 
liver diseases: relationship to severity of liver diseases, presence of esophageal varices, and 
hyperdynamic circulation. J Hepatol. 1995;22(2):165-72. Epub 1995/02/01. 
14. 
Mutlu E, Keshavarzian A, Engen P, Forsyth CB, Sikaroodi M, Gillevet P. Intestinal dysbiosis: 
a possible mechanism of alcohol-induced endotoxemia and alcoholic steatohepatitis in rats. Alcohol 
Clin Exp Res. 2009;33(10):1836-46. Epub 2009/08/04. 
15. 
Whitfield K, Rambaldi A, Wetterslev J, C G. Pentoxifylline for alcoholic hepatitis (Review). 
Cochrane Database of Systematic Reviews. 2009(4). 
16. 
McCullough AJ, O'Connor JF. Alcoholic liver disease: proposed recommendations for the 
American College of Gastroenterology. Am J Gastroenterol. 1998;93(11):2022-36. Epub 1998/11/20. 
17. 
JJ L, GL G, LH G, RD A. Anticore antibody screening of transfused blood. Vox Sang1978. p. 
77- 80. 
18. 
Lachin JM, Foulkes MA. Evaluation of sample size and power for analyses of survival with 
allowance for nonuniform patient entry, losses to follow-up, noncompliance, and stratification. 
Biometrics. 1986;42(3):507-19. Epub 1986/09/01. 
19. 
Hintze J. PASS 11. Kaysville, Utah, USA: NCSS, LLC; www.ncss.com; 2011. 

ICF_001.pdf: 
Informed Consent forms 
 
Official title: Novel Therapies in Moderately Severe Acute Alcoholic 
Hepatitis 
 
 
 
NCT number: NCT01922895 
IRB Approved date: September 13, 2017 


Page 1 of 6
DO NOT FILE OR SCAN THIS CONSENT FORM INTO THE MEDICAL RECORD
The University of Texas Southwestern Medical Center at Dallas
Parkland Health & Hospital System
CONSENT TO PARTICIPATE IN RESEARCH
Title of Research:
Novel therapies in moderately severe alcoholic hepatitis
Funding Agency/Sponsor:
NIH (funded)
Study Doctors:
Mack Mitchell, M.D.
Lisa Casey, M.D.
Jennifer Cuthbert, M.D.
Study Personnel
Co-Investigator:
Blair Holbein, Ph.D.
You may call these study doctors or research personnel during regular office hours at 214-648-
4570. At other times, you may call them at 214-648-3111 and tell them that you need to contact 
your study doctors. Have the study information with you when you call after hours so that the 
hospital operators know who to contact.
Instructions:
Please read this consent form carefully and take your time making a decision about whether to 
participate.  As the researchers discuss this consent form with you, please ask him/her to 
explain any words or information that you do not clearly understand.  The purpose of the study, 
risks, inconveniences, discomforts, and other important information about the study are listed 
below.  If you decide to participate, you will be given a copy of this form to keep.
What you should know about this study:  

You are being asked to join a research study.  

This consent form explains the research study and your part in the study.  

Please read it carefully and take as much time as you need. 

Please ask questions at any time about anything you do not understand 

You are a volunteer.  If you join the study, you can change your mind later. You can 
decide not to take part or you can quit at any time. There will be no penalty or loss of 
benefits if you decide to quit the study.  

If you are not scheduled to undergo a procedure for clinical reasons, you must be an 
adult with the capacity to give consent in order to provide blood or spinal fluid.

During the study we will tell you if we learn any new information that might affect whether 
you wish to continue to be in the study.

Ask your study doctor or the study team to explain any words or information in this 
informed consent that you do not understand.
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 2 of 6
DO NOT FILE OR SCAN THIS CONSENT FORM INTO THE MEDICAL RECORD
Why is this research being done?
The purpose of this study is to start an electronic database for patient information and to collect 
blood, tissue and other samples from people, being evaluated or treated for liver inflammation 
(hepatitis) from alcohol. 
We are collecting these samples and medical information so that they can be made available to 
research scientists who are involved in the study of these diseases. This research is attempting 
to improve upon our ability to diagnose these conditions.
What will happen if you join this study?
If you agree to be in this study, we will ask you to do the following things:
Medical Record Review:  Your medical records will be reviewed by a member of our 
team and selective data will be entered into a secure electronic database.  This will 
include history and physical examination, results of x-rays, pathology, blood counts, 
clotting, and chemistry tests for the liver. Medical records will be reviewed on a regular 
basis to ensure up to date information.
Specimen Samples:  If as part of your clinical care, a blood draw or biopsy is performed, 
some of the fluid or tissue will be placed into our repository for future research studies. 
You may also be asked to consent to a blood draw to collect samples solely for research 
purposes (only if you are an adult with capacity to give consent). You do not need to 
provide these samples to be part of the database.
For identification purposes, you will be assigned a coded identifier and will not be 
personally identifiable.  This code will be placed on all the material that is sent to the 
research laboratories. 
Information about your medical history, portions of samples and results of tests may be shared 
with national and international research partners and may be entered into secondary national 
and international databases. The sharing of this information is meant to increase collaborative 
projects and bolster worldwide research efforts. The information provided to them will not 
include your name, medical record number or unique identifiers. It may include your age, date of 
birth, city of residence or dates of tests.
Will I be contacted again?
Yes, you may also be contacted if updated medical information is needed for the database.
Will my specimen be stored for future use?
Yes, your blood specimens or other samples will be evaluated by research scientists studying 
various liver diseases.  Some portion may be frozen or stored indefinitely for this future use.  
Stored specimens may be analyzed in the future using additional technologies without you 
being asked to sign another consent form.  
Will my samples be used to study any other diseases besides my condition?
Yes. An important part of this research is to allow for associations to be made between different 
diseases. Your sample may be used for broad-based research for a variety of disease states.
Will my sample be used for genetic research?
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 3 of 6
DO NOT FILE OR SCAN THIS CONSENT FORM INTO THE MEDICAL RECORD
Yes.  Genetic research is an important part of the investigation into the causes of these 
diseases.  The causes of many of these diseases are believed to be the result of combinations 
of inherited genes and possible various exposures to the environment.  Genetic research is an 
important part of the investigation into the causes of these diseases. There are no plans to 
inform you, or your relatives, about the results of genetic studies, since at this time the 
information is not thought to be medically useful.
What is DNA?
DNA means deoxyribonucleic acid.  DNA is the substance in our cells which contains 
information we inherited from our parents and other family members. Your DNA contains 
“genes” which predict things like physical characteristics (eye color, hair color, height, etc.) and 
may also be a factor in whether you develop or are at risk of developing certain illnesses or 
disorders.
How is DNA obtained? Cells from blood or other body materials are processed in a laboratory 
that has special equipment that can extract DNA and identify genes.
What are the risks or discomforts of the study?
There is a risk that your personal health information could be seen by people not working on the 
study.  
The risks of a blood draw include pain, bruising and same patients have lost consciousness 
during the process. 
Collection of the Tissue Samples: You may undergo a liver biopsy for your liver disease. If this 
is planned, your doctor will have discussed this with you.  This procedure has been deemed 
medically necessary and you have agreed to the procedure.  Participation in this research will 
mostly involve using what is called “medical waste.”  Medical waste is leftover tissue that is not 
needed for diagnosis of your liver disease.
Because all specimens obtained for research will come from your routinely scheduled 
procedures, there will be no additional risk or discomfort related to participating in this research.  
The only potential risk to you is accidental release of your medical information.  
Problems obtaining insurance or employment
A new Federal Law called the Genetic Information Nondiscrimination Act of 2008 (GINA), 
generally makes it illegal for group and individual health insurers from using your genetic 
information to set insurance eligibility, premiums, or contribution amounts.  They cannot request 
or require that you take a genetic test. In addition, employers with 15 or more employees may 
not use your genetic information to make decisions regarding hiring, firing, job assignments, or 
promotions, nor can they request, require, or purchase your genetic information. GINA does not 
protect you against genetic discrimination by companies that sell life, disability, or long-term 
care insurance.
Are there risks related to pregnancy?
The risks in pregnancy are the same as the general risks of the study, outlined above. Patients 
who are concerned about their pregnancy should discuss any concerns with their obstetrician 
before taking part in the study.
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 4 of 6
DO NOT FILE OR SCAN THIS CONSENT FORM INTO THE MEDICAL RECORD
What should I do if I think I am having problems?
If you have unusual symptoms, pain, or any other problems while you are in the study, you 
should report them to the researchers right away.  Telephone numbers where they can be 
reached are listed on the first page of this consent form.
If you have a sudden, serious problem, like difficulty breathing or severe pain, go to the nearest 
hospital emergency room, or call 911 (or the correct emergency telephone number in your 
area).  Tell emergency personnel about any medications you are taking, including any 
medications you are taking for this study.  
Are there benefits to being in the study?
There will be no direct medical benefit to you.  Since it is possible that the causes of one, some 
or all of the liver diseases could be determined because of research using your samples, 
someone may benefit in the future.
What are your options if you do not want to be in the study?
You do not have to join this study.  If you do not join, your care will not be affected.
Will it cost you anything to be in this study?
No.
Will you be paid if you join this study?
No.
Can you leave the study early?
Yes. You may withdraw your consent by contacting your study doctor, Dr. Mitchell at 214-648-
4570 during regular business hours and at 214-648-3111 after hours and on weekends and 
holidays.  However, samples that have been already used for research, as well as any results or 
information already collected before you withdraw from the study, cannot be destroyed.  
Refusing to take part in the future will not affect your current or future medical care in any way.  
If you withdraw from this study at any time, we will stop contacting you.
Will my information be kept confidential?
Medical information collected during this study and the results of any test or procedure done 
may be included in your medical record and this information may be available to health care 
providers and authorized persons including your insurance company.
You should know that certain organizations that may look at and/or copy your medical records 
for research, quality assurance, and data analysis include:
•
Cleveland Clinic, University of Louisville, University of Massachusetts, NIH
•
Representatives of government agencies, like the U.S. Food and Drug Administration 
(FDA), involved in keeping research safe for people; and
•
The UT Southwestern Institutional Review Board. 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law.  This Web site will not include information that can identify you.  At most, the Web site 
will include a summary of the results.  You can search this Web site at any time.
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 5 of 6
DO NOT FILE OR SCAN THIS CONSENT FORM INTO THE MEDICAL RECORD
In addition to this consent form, you will be asked to sign an "Authorization for Use and 
Disclosure of Protected Health Information." This authorization will give more details about how 
your information will be used for this research study, and who may see and/or get copies of your 
information.
If you do cancel your permission to use and disclose your information, your part in this study will 
end and no further information about you will be collected. Your cancellation would not affect 
information already collected in this study.
What will happen if I am harmed as a result of taking part in this study?
Compensation for an injury resulting from your participation in this research is not available from 
the University of Texas Southwestern Medical Center at Dallas or Parkland Health & Hospital 
System.
You retain your legal rights during your participation in this research
What happens to Data, Tissue, Blood and Specimens that are collected in the study?
Researchers at UT Southwestern work to find the causes and cures of disease. The data, 
tissue, blood and specimens collected from you during this study are important to both this 
study and to future research.
If you join this study:

You will not own the data, or the tissue, blood, or other specimens given by you to the 
investigators for this research.

Both UT Southwestern and any sponsor of this research may study your data and the 
tissue, blood, or other specimens collected from you.

If data, tissue, blood, or other specimens are in a form that identifies you, UT 
Southwestern may use them for future research only with your consent or IRB approval.

You will not own any product or idea created by the researchers working on this study.

You will not receive any financial benefit from the creation, use or sale of such a product 
or idea.
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 6 of 6
DO NOT FILE OR SCAN THIS CONSENT FORM INTO THE MEDICAL RECORD
SIGNATURES:
YOU WILL BE GIVEN A COPY OF THIS CONSENT FORM TO KEEP.
Your signature below certifies the following:

You have read (or been read) the information provided above.

You have received answers to all of your questions and have been told who to call if you 
have any more questions.

You have freely decided to participate in this research.

You understand that you are not giving up any of your legal rights.

You understand that a copy of this signed consent document, information about this 
study and the results of any test or procedure done may be included in your medical 
record and this information may be available to health care providers and authorized 
persons including your insurance company.
Signature of Participant       
(18 yrs or older)
Printed Name of Participant 
(18 yrs or older)
Date
Time
AM/PM
NAME OF PERSON OBTAINING CONSENT
Signature 
Printed Name 
Date
Time
AM/PM
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 1 of 14
DO NOT DISCLOSE
The University of Texas Southwestern Medical Center at Dallas
Parkland Health & Hospital System
CONSENT TO PARTICIPATE IN RESEARCH
Title of Research:                    Novel therapies in moderately severe alcoholic hepatitis
Funding Agency/Sponsor:      NIH (funded)
Study Doctors:                        Mack Mitchell, M.D.
Lisa Casey, M.D. 
Jennifer Cuthbert, M.D.
You may call these study doctors or research personnel during regular office hours at 214-
648-4570.  At other times, you may call them at 214-648-3111 and tell them that you need to 
contact your study doctors. Have the study information with you when you call after hours so 
that the hospital operators know who to contact.
Instructions:
Please read this consent form carefully and take your time making a decision about whether 
to participate.  As the researchers discuss this consent form with you, please ask him/her to 
explain any words or information that you do not clearly understand.  The purpose of the 
study, risks, inconveniences, discomforts, and other important information about the study 
are listed below. If you decide to participate, you will be given a copy of this form to keep.
Why is this study being done?
This study is being done to find out whether supplementing your diet, with a special nutrient, 
can treat your condition better or more safely than standard medicine.
Why is this considered research?
This is a research study because the dietary supplement is not recognized for the treatment 
of patients with liver problems.
The following definitions may help you understand this study:
•
Double-blind means neither you nor the researchers will know which drug you are 
receiving.
•
Placebo-controlled means that some participants will get a placebo. A placebo looks 
like the investigational drug but it includes no active ingredients.
•
Randomization means you will be placed by chance (like a flip of a coin) in one of the 
study groups.
•
Standard medical care means the regular care you would receive from your personal 
doctor if you choose not to participate in this research.
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 2 of 14
DO NOT DISCLOSE
•  Researcher means the study doctors and research personnel at the University of
Texas Southwestern Medical Center at Dallas and its affiliated hospitals.
Why am I being asked to take part in this research study?
You are being asked to take part in this study because you have an inflamed liver (hepatitis)
that your doctors’ think is from your body’s reaction to alcohol.
Do I have to take part in this research study?”
No.  You have the right to choose whether you want to take part in this research study. If you 
decide to participate and later change your mind, you are free to stop participation at any 
time. If you decide not to take part in this research study it will not change your legal rights or 
the quality of health care that you receive at this center.
How many people will take part in this study?
About 50 people will take part in this study at UT Southwestern or Parkland Health and 
Hospital System. This study also is taking place at a number of other medical facilities around 
the country. There will be a total of 130 people participating in this research study throughout 
the United States.
What is involved in the study?
If you volunteer to take part in this research study, you will be asked to sign this consent form 
and will have the following tests and procedures.  Some of the procedures may be part of 
your standard medical care, but others are being done solely for the purpose of this study.
Screening Procedures
To help decide if you qualify to be in this study, the researchers will ask you questions 
about your health, including medications you take, your diet and habits. They will also get 
information from your medical record.
Group Assignment
If the researchers believe you can take part in this study, you will be assigned randomly 
(like a flip of a coin) to receive either an active diet supplement or an inactive one (a 
placebo).
For 6 months, everyone gets an identical-appearing supplement. If the researchers knew 
which patients were getting the study drug they might be tempted to favor it.
All study supplements will finish after 6 months.
The group you will be in is decided by your study number.  This is linked to instructions 
that are kept in the hospital pharmacy.   The pharmacy will provide you with your 
medications when you are in the hospital and also give you your medications to take at 
home.  Neither you nor the researchers will be allowed to choose which group you are 
assigned to; neither you nor the researchers will know which group you are in.
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 3 of 14
DO NOT DISCLOSE
Study Medication/Intervention
If you decide to participate in this study you will take a supplement to your diet every day 
for 6 months. The supplement is Culturelle (Lactobacillus Rhamnosus GG).
Procedures and Evaluations during the Research
All study subjects will receive the standard medical care used for hepatitis from your body’s 
reaction to alcohol. This includes:
1.  A good diet while in the hospital and recommendations for what to eat at home 
a.  Lots of fresh vegetables, fruits, chicken, fish
b.  Vitamins and other special nutrition if needed
2.  Help with avoiding alcohol in the future 
a.  Counselors
b.  Psychologists
c.  Rehabilitation assistance
3.  Only take medications prescribed by your doctors. Do not take any medication or diet 
supplement or over-the-counter remedy without checking with a study doctor or nurse. 
Avoid all pain medicines that have high risk associated with them because of liver 
disease.
a.  Aspirin and over the counter medications like ibuprofen Motrin®, Aleve® can 
damage the kidneys with as little as one tablet
b.  Stronger pain medicines that contain codeine or a similar agent can cause 
confusion related to liver disease
c.  Acetaminophen (Tylenol®) can directly cause liver damage
4.  Treatment for any complications that can occur 
a.  Antibiotics for infections
b.  Treatment for diarrhea or constipation or nausea and vomiting if they occur
5.  Blood drawing to follow the changes in your liver.
6.  Follow-up in the regular outpatient liver clinic, after you leave the hospital, until your 
liver has completely recovered. The number of visits depends on how quickly you get 
better. This is likely to be:
a.  1 week after leaving the hospital 
b.  1 – 2 visits in the next month
c.  1 – 2 visits in the next 2 – 4 months, depending on how quickly you get well 
d.  A final clinic visit after 6 months
In addition, the following special, extra studies will be done for research purposes:
Where
When
What
How
In hospital
First
day
of
the 
study
Inflammation markers and liver
markers will be measured. These 
tests are done as part of the 
research on treatment for your 
condition.
A nutritional assessment with a 
hand grip dynamometer.
Research tests:
Taking extra tubes of blood 
when you have regular 
blood tests (amount = 3 
tablespoons). 
Collecting 
urine in a
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 4of 14
DO NOT DISCLOSE
Blood, stool, and urine for testing 
to see why alcohol caused your 
body to react in this way. These 
tests are done as part of the 
standard 
treatment for your 
condition.
container. Collecting stool
in a container.
In clinic
7 day
1 month
3 months
6 months
Inflammation markers and liver
markers will be measured. These 
tests are done as part of the 
research on treatment for your 
condition.
Blood and urine for testing to see 
why alcohol caused your body to 
react in this way. These tests are 
done as part of the standard 
treatment for your condition.
Research tests:
Taking extra tubes of blood 
when you have regular 
blood tests (amount = 3 
tablespoons). 
Collecting 
urine 
and 
stool 
in 
a 
container.
The inflammation and liver markers in this study are designed for research, not for medical 
purposes. They are not useful for finding problems or diseases. Even though the researchers 
are not looking at your inflammation and liver markers to find or treat a medical problem, you 
will be told if they notice something unusual.   You and your regular doctor can decide 
together whether to follow up with more tests or treatment.  Because the inflammation and 
liver markers done in this study are not for medical purposes, the research results will not be 
sent to you or to your regular doctor. Your anonymous sample will be sent to coordinating 
research centers outside of UT Southwestern who are studying your disease. Your sample 
will be made anonymous by removing any identifiable information about you before it is 
shared with investigators outside of UT Southwestern.
Study Procedures by Study Day:
A summary of evaluations is located in the schedule of events table provided at the end of 
this section. The procedures and evaluations are outlined below.
Screening:
Complete screening will occur once the informed consent has been obtained as described 
above. Individuals who are not eligible for the study will be given the option for the same 
follow-up without the study medicine.
The study subject’s general health and study information include:
•
Signed consent
•
Other routine information including sex, date of birth, race and ethnic group (Hispanic 
or not).
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 5 of 14
DO NOT DISCLOSE
•
Medicine history over the past 30 days, including prescribed and over-the-counter 
ones, herbal remedies, vitamins and minerals.
•
Alcohol in the past 60 days and for the years before.
•
Drawing blood for blood counts, clotting, and chemistry tests for the liver, pancreas 
and kidneys; female study subjects will have a pregnancy test. These are standard 
tests for your condition. The total amount of blood for these tests is about 7 
tablespoons.
•
Physical examination, including height, weight, and vital signs (blood pressure, pulse, 
breathing and temperature)
•
Imaging of the abdomen.
Assessments at baseline and during study treatment:
Study Procedures by Study Day:
A summary is in the table at the end of this section.
Study day 0 – start (within 48 hours of study beginning)
•
Record health history and review alcohol use.
•
Standard of care laboratory studies (chemistry, blood count, clotting, urine, infection 
including tuberculosis testing).
•
Tests for fluid in belly, if it is there
•
Nutritional Assessment with a hand grip measurement.
•
Urine, blood (3 tablespoons) and stool testing for research.
•
Make a list of all medicines including those purchased over the counter, from health 
food stores and other remedies.
•
Check blood pressure, pulse, temperature and breathing (vital signs) and physical 
exam.
Treatment day 1 – time zero
•
Begin study medicine once daily.
•
Standard blood tests for your condition (1 tablespoon)
Treatment day 2:
•
Inpatient assessment to include:
•
Review health history for changes.
•
List all medicines
•
Check vital signs and physical exam
•
Research studies (urine and ½ tablespoon of blood).
•
24 hour urine collection.
•
Continue study medicine once daily.
•
Standard blood tests for your condition (1½ tablespoons)
Treatment days 3-6:
•
If study subject remains inpatient or has outpatient visit:
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 6 of 14
DO NOT DISCLOSE
•
Review health history for changes. .
•
List all medicines
•
Check vital signs and physical exam
•
Continue study medicine once daily.
•
Standard blood tests for your condition (1 tablespoon)
Treatment day 7 ± 2 days:
•
Inpatient assessment or required outpatient clinic visit to include:
•
Review health history for changes. Review alcohol intake.
•
List all medicines
•
Check vital signs and physical exam
•
Research studies (urine and 2 tablespoon of blood).
•
Continue study medicine once daily.
•
Standard and research blood tests (2 tablespoons)

Nutritional Assessment with hand grip measurement.
Treatment days 8-14:
•
If study subject remains inpatient or has outpatient visit:
•
Review health history for changes. Review alcohol intake.
•
List all medicines
•
Check vital signs and physical exam
•
Continue study medicine once daily.
•
Standard blood tests for your condition (1 tablespoon)
Treatment days 15-27:
•
If study subject remains inpatient or has a clinically indicated outpatient visit:
•
Review health history for changes. Review alcohol intake.
•
List all medicines
•
Check vital signs and physical exam
•
Continue study medicine once daily.
•
Standard blood tests for your condition (1 tablespoons)
Treatment day 28 ± 2 days:
•
Inpatient assessment or required outpatient clinic visit to include:
•
Review health history for changes. Review alcohol intake.
•
List all medicines
•
Check vital signs and physical exam
•
Research studies (urine and 3 tablespoon blood).
•
Continue study medicine once daily.
•
Standard and blood tests for your condition (1½ tablespoon)

Nutritional Assessment with hand grip measurement
Treatment day 29 to 2 months:
•
Continue study medicine once daily.
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 7 of 14
DO NOT DISCLOSE
•
If study subject remains inpatient during this interval or completes clinically indicated 
outpatient visit during this time, the following data will be recorded:
•
Review health history for changes. Review alcohol intake.
•
List all medicines
•
Check vital signs and physical exam
•
Standard blood tests for your condition (1 tablespoons)
Treatment 3 months ± 2 weeks:
•
Inpatient assessment or required outpatient clinic visit to include:
•
Review health history for changes. Review alcohol intake.
•
List all medicines
•
Check vital signs and physical exam
•
Research studies (urine, stool, and 3 tablespoon blood).
•
Continue study medicine once daily
•
Standard blood tests for your condition (1½ tablespoon)
Treatment 4, 5 months ± 2 weeks:
•
Continue study medicine once daily
•
If  study subject remains inpatient or  completes clinically indicated outpatient visit 
during this time, the following will be done:
•
Review health history for changes. Review alcohol intake.
•
List all medicines
•
Check vital signs and physical exam
•
Standard blood tests for your condition (1 tablespoons)
Treatment 6 months ± 2 weeks:
•
STOP study medicines.
•
Complete abdominal ultrasound.
•
Inpatient assessment or required outpatient clinic visit to include:
•
Review health history for changes. Review alcohol intake.
•
List all medicines
•
Check vital signs and physical exam
•
Research studies (urine, 3 tablespoon blood and stool).
•
Standard blood tests for your condition (1½ tablespoons)

Nutritional Assessment with hand grip measurement
Follow up of early end of study:
A safety visit will be done about 30 days after stopping of study medicine for all study 
subjects who stopped before the end. . This will include:
•
Standard blood tests for your condition (chemistry, blood count and clotting).
•
Check vital signs and physical exam
•
Review health history for changes. Review alcohol intake.
•
List all medicines
•
Review reason for early stopping.
•
Standard and research blood tests (2 tablespoons total)
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 8 of 14
DO NOT DISCLOSE
Purpose
Test
Day 0
Day
2 – 6*
Day 7
Day
8 – 27*
Day
28
2 mos*
3 mos
4 mos*
5 mos*
6 mos
Standard
General health and liver questions
x
x
x
x
x
x
x
x
x
x
Questions about drinking alcohol
x
x
x
x
x
x
x
x
x
x
Physical exam
x
x
x
x
x
x
x
x
x
x
Blood
Liver tests
x
x
x
x
x
x
x
x
x
x
Tests of chemicals and kidneys
x
x
x
x
x
x
x
x
x
x
Blood count
x
x
x
x
x
x
x
x
x
x
Cholesterol test
x
x
Pancreas tests
x
Tests for viruses and bacteria
x
TB skin test
x
Urine
Urine tests
x
Poisons
x
Fluid
Belly fluid chemicals and infection
x
Stool
Infection tests
x
Imaging
Ultrasound of belly
x
x
Research
Gut leakiness
x
x
x
x
Zinc levels
x
x
 x
x
Stool bacteria tests
x
 x
x
Inflammation tests
x
x-day 2
x
x
x
x
* if clinically indicated
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 9 of 14
DO NOT DISCLOSE
Procedures for storing of extra or left over samples
Samples of your blood and urine will be frozen and stored so that the researchers 
can test for any new inflammation or liver markers that are developed.
•
Samples will be labeled with a study number, not with your name or other 
personal number.
•
The key for study numbers will be kept in your medical record in a special 
section for research study information.
•
The anonymous samples will be sent to Cleveland Clinic for storage
•
The Principal Investigators will decide where and how the remaining samples 
will be processed
•
Samples may be sent to other scientists for studies approved by their local
IRB’s to further understand this disease.
How long can I expect to be in this study?
The study is for a total of 6 months, 6 months on tablets. You can choose to stop 
participating for any reason at any time. However, if you decide to stop participating in 
the study, we encourage you to tell the researchers.  You will be asked if you are willing 
to complete some study termination tests.
What are the risks of the study?
Study Procedure/Intervention
Because of your participation in this study, you are at risk for the following side effects. 
You should discuss these with the researchers and your regular health care provider.
Dietary Supplement (Probiotics): Bacteria are normally found in the gastrointestinal 
tract. They are deliberately cultured in yogurts and are a nutritional supplement.
Side effects
Frequent
>20% of subjects
Occasional
2 - 20% of subjects
Rare
Less than 2% of subjects
Serious
Infection
with
probiotic
bacteria (1 adult)
Less Serious
Minor
Burping
Hiccups
Psychological Stress
Some of the questions we will ask you about your personal habits, as part of this study, 
may make you feel uncomfortable.  You may refuse to answer any of the questions, 
take a break or stop your participation in this study at any time.
Loss of Confidentiality
Any time information is collected; there is a potential risk for loss of confidentiality.
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 10 of 14
DO NOT DISCLOSE
Every effort will be made to keep your information confidential; however, this cannot be 
guaranteed.
Risks of Blood Drawing
Risks associated with drawing blood from your arm include minimal discomfort and/or 
bruising.  Infection, excess bleeding, clotting, and/or fainting also are possible, although 
unlikely. You will have You will have 6 tablespoons of blood collected because you are 
in this research study, in addition to the tests that you need to take care of your health 
(another 13 tbspns over the 6 months).
Other Risks
There may possibly be other side effects that are unknown at this time. If you are 
concerned about other, unknown side effects, please discuss this with the researchers.
How will risks be minimized or prevented?
Potential risks and discomforts will be minimized to the greatest extent possible by 
appropriate training of all researchers and study personnel, monitoring you closely, 
withdrawal from the study upon evidence of difficulty or an adverse event; referral for 
treatment, counseling or other necessary follow-up.
What will my responsibilities be during the study?
While you are part of this study, the researchers will follow you closely to determine 
whether there are problems that need medical care.  It is your responsibility to do the 
following:
•
Ask questions about anything you do not understand.
•
Keep your appointments.
•
Follow the researchers’ instructions.
•
Let the researchers know if your telephone number or address changes.
•
Store study tablets in a secure place at home away from anyone who is unable 
to read and understand labels, especially children.
•
Tell the researchers before you take any new medication, even if it is prescribed 
by another doctor for a different medical problem or something purchased over 
the counter.
•
Tell your regular doctor about your participation in this study.
•
Carry information about contacting the study doctors in your purse or wallet.
•
Report to the researchers any injury or illnesses while you are on study, even if 
you do not think they are related.
If I agree to take part in this research study, will I be told of any new risks that 
may be found during the course of the study?
Yes.  You will be told if any new information becomes available during the study that 
could cause you to change your mind about continuing to participate or that is important 
to your health or safety.
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 11 of 14
DO NOT DISCLOSE
What should I do if I think I am having problems?
If you have unusual symptoms, pain, or any other problems while you are in the study, 
you should report them to the researchers right away.  Telephone numbers where they 
can be reached are listed on the first page of this consent form. If you have a sudden, 
serious problem, like difficulty breathing or severe pain, go to the nearest hospital 
emergency room, or call 911 (or the correct emergency telephone number in your area). 
Tell emergency personnel about any medications you are taking, including any 
medications you are taking for this study.
What are the possible benefits of this study?
If you agree to take part in this study, there may or may not be direct benefits to you. 
The researchers cannot guarantee that you will benefit from participation in this 
research. We hope that the information learned from this study will benefit others with 
inflammation of the liver from alcohol.  Information gained from this research could lead 
to treatment with lower risks of dying in the first 6 months after being admitted to the 
hospital for hepatitis from alcohol.
What options are available if I decide not to take part in this research study?
You do not have to participate in this research to receive care for your medical problem. 
Instead of being in this study, you have the following option:
•
Standard  of  care  treatment  through  abstinence  from  alcohol  and  general 
supportive care (nutritional support and hydration)
Please talk to the researchers or your personal doctor about these options.
Will I be paid if I take part in this research study?
There are no funds available to pay for parking expenses, transportation to and from the 
research center, lost time away from work etc., lost wages, or child care expenses.
Will my insurance provider or I be charged for the costs of any part of this 
research study?
No. Neither you, nor your insurance provider, will be charged for anything done only for 
this research study. However, the standard medical care for your condition (care you 
would have received whether or not you were in this study) is your responsibility (or the 
responsibility  of  your  insurance  provider  or  governmental  program).    You  will  be 
charged, in the standard manner, for any procedures performed for your standard 
medical care.
What will happen if I am harmed as a result of taking part in this study?
It is important that you report any illness or injury to the research team listed at the top 
of this form immediately. Compensation for an injury resulting from your participation in 
this research is not available from the University of Texas Southwestern Medical Center 
or Parkland Health & Hospital System. You retain your legal rights during your 
participation in this research
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 12 of 14
DO NOT DISCLOSE
Can I stop taking part in this research study?
Yes.  If you decide to participate and later change your mind, you are free to stop taking 
part in the research study at any time. If you decide to stop taking part in this research 
study, it will not affect your relationship with the UT Southwestern staff or doctors. 
Whether you participate or not will have no effect on your legal rights or the quality of 
your health care.
If I agree to take part in this research study, can I be removed from the study 
without my consent?
Yes. The researchers may decide to take you off this study if:
•
Your medical problem becomes worse.
•
The researchers believe that participation in the research is no longer safe for 
you.
•
You are unable to follow the researcher’s instructions.
Will my information be kept confidential?
Medical information collected during this study and the results of any test or procedure 
done may be included in your medical record and this information may be available to 
health care providers and authorized persons including your insurance company.
You should know that certain organizations that may look at and/or copy your medical 
records for research, quality assurance, and data analysis include:
•
Cleveland Clinic, University of Louisville, University of Massachusetts, NIH
•
Representatives  of  government  agencies,
like
the  U.S.
Food
and
Drug
Administration (FDA), involved in keeping research safe for people; and
•
The UT Southwestern Institutional Review Board.
A description of this clinical trial will be available on http://www.clinicaltrials.gov, as 
required by the U.S. Law.  This Web site will not include information that can identify 
you.  At most, the Web site will include a summary of the results.  You can search this 
Web site at any time.
In addition to this consent form, you will be asked to sign an "Authorization for Use and 
Disclosure of Protected Health Information."  This authorization will give more details 
about how your information will be used for this research study, and who may see 
and/or get copies of your information.
Are there procedures I should follow after stopping participation in this research? 
Yes.  If you, the researchers, or the sponsor stops your participation in the research, 
you may be asked to do the following:
•
Let  the  researchers know  immediately that  you  wish  to  withdraw from  the 
research.
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 13 of 14
DO NOT DISCLOSE
•
Return to the research center for tests that may be needed for your safety.
•
Return any unused study materials, including empty containers.
•
Discuss your  future medical care,  if  any,  with  the  researchers and/or your 
personal doctor.
Whom do I call if I have questions or problems?
For questions about the study, contact Dr. Mitchell at 214-648-4570 during regular 
business hours and at 214-648-3111 after hours and on weekends and holidays.
For questions about your rights as a research participant, contact the UT Southwestern
Institutional Review Board (IRB) Office at 214-648-3060.
SIGNATURES:
YOU WILL BE GIVEN A COPY OF THIS CONSENT FORM TO KEEP.
Your signature below certifies the following:
•
You have read (or been read) the information provided above.
•
You have received answers to all of your questions and have been told who to 
call if you have any more questions.
•
You have freely decided to participate in this research.
•
You understand that you are not giving up any of your legal rights.
•
You understand that a copy of this signed consent document, information about 
this study and the results of any test or procedure done may be included in your 
medical record and this information may be available to health care providers 
and authorized persons including your insurance company.
Participant’s Name (printed)
Participant’s Signature
Date & Time
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 14 of 14
DO NOT DISCLOSE
Name of person obtaining consent (printed)
Signature of person obtaining consent
Date & Time
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 1 of 8
DO NOT DISCLOSE
The University of Texas Southwestern Medical Center at Dallas
Parkland Health & Hospital System
CONSENT TO PARTICIPATE IN RESEARCH
Title of Research:
Novel therapies in moderately severe alcoholic hepatitis
Funding Agency/Sponsor:
NIH (funded)
Study Doctors:
Mack Mitchell, M.D.
Lisa Casey, M.D.
Jennifer Cuthbert, M.D.
You may call these study doctors or research personnel during regular office hours at 214-648-
4570.  At other times, you may call them at 214-648-3111 and tell them that you need to contact 
your study doctors. Have the study information with you when you call after hours so that the 
hospital operators know who to contact.
Instructions:
Please read this consent form carefully and take your time making a decision about whether to 
participate.  As the researchers discuss this consent form with you, please ask him/her to explain 
any words or information that you do not clearly understand.  The purpose of the study, risks, 
inconveniences, discomforts, and other important information about the study are listed below.  If 
you decide to participate, you will be given a copy of this form to keep.
Why is this study being done?
This study is being done to follow what happens to the liver in response to inflammation from 
alcohol by collecting and testing research samples. The research studies will not improve the 
health of your liver. 
Why is this considered research? 
This is a research study because the tests are not routine for patients with liver problems. 
The following definitions may help you understand this study: 

Standard medical care means the regular care you would receive from your personal 
doctor if you choose not to participate in this research.

Researcher means the study doctors and research personnel at the University of Texas 
Southwestern Medical Center at Dallas and its affiliated hospitals.
Why am I being asked to take part in this research study?
You are being asked to take part in this study because you have an inflamed liver (hepatitis) that 
your doctors’ think is from your body’s reaction to alcohol. 
Do I have to take part in this research study?
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 2 of 8
DO NOT DISCLOSE
No.  You have the right to choose whether you want to take part in this research study.  If you 
decide to participate and later change your mind, you are free to stop participation at any time. If 
you decide not to take part in this research study it will not change your legal rights or the quality 
of health care that you receive at this center.
How many people will take part in this study?
About 50 people will take part in the medication study at UT Southwestern or Parkland Health 
and Hospital System. This study also is taking place at a number of other medical facilities around 
the country. There will be a total of 130 people participating in this research study throughout the 
United States. People who don’t want to take a medication can be part of the research by 
participating in the new tests. 
What is involved in the study?
If you volunteer to take part in this research study, you will be asked to sign this consent form and 
will have the following tests and procedures.  Some of the procedures may be part of your 
standard medical care, but others are being done solely for the purpose of this study.
Screening Procedures
To help decide if you qualify to be in this study, the researchers will ask you questions about 
your health, including medications you take, your diet and habits. They will also get information 
from your medical record. 
Procedures and Evaluations during the Research
All study subjects will receive the standard medical care used for patients with hepatitis from your 
body’s reaction to alcohol. This includes:
1.
A good diet while in the hospital and recommendations for what to eat at home
a.
Lots of fresh vegetables, fruits, chicken, fish
b.
Vitamins and other special nutrition if needed
2.
Help with avoiding alcohol in the future
a.
Counselors
b.
Psychologists
c.
Rehabilitation assistance
3.
Only take medications prescribed by your doctors. Do not take any medication or diet 
supplement or over-the-counter remedy without checking with a study doctor or nurse. 
Avoid all pain medicines that have high risk associated with them because of liver disease.
a.
Aspirin and over the counter medications like ibuprofen Motrin®, Aleve® can 
damage the kidneys with as little as one tablet
b.
Stronger pain medicines that contain codeine or a similar agent can cause 
confusion related to liver disease
c.
Acetaminophen (Tylenol®) can directly cause liver damage 
4.
Treatment for any complications that can occur
a.
Antibiotics for infections
b.
Treatment for diarrhea or constipation or nausea and vomiting if they occur
5.
Blood drawing to follow the changes in your liver. 
6.
Follow-up in the regular outpatient liver clinic, after you leave the hospital, until your liver 
has completely recovered. The number of visits depends on how quickly you get better. 
This is likely to be:
a.
1 week after leaving the hospital 
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 3 of 8
DO NOT DISCLOSE
b.
1 – 2 visits in the next month 
c.
1 – 2 visits in the next 2 – 4 months, depending on how quickly you get well 
d.
A final clinic visit after 6 months 
In addition, the following special, extra studies will be done for research purposes when you come 
into clinic:
Where
When
What
How
In 
hospital
First 
day 
of 
the 
study
Inflammation markers and liver markers 
will be measured.  These tests are done 
as part of the research on treatment for 
your condition.
A measure of nutritional status will be 
obtained via a hand grip measurement 
with the JAMAR dynamometer.  
Blood and urine for testing to see why 
alcohol caused your body to react in this 
way. These tests are done as part of the 
standard treatment for your condition. 
Research tests: 
Taking extra tubes of blood 
when you have regular 
blood tests (amount = 3 
tablespoons). 
Collecting 
urine 
in 
a 
container. 
Collecting 
stool 
in 
a 
container.
The inflammation and liver markers in this study are designed for research, not for medical 
purposes. They are not useful for finding problems or diseases.  Even though the researchers are 
not looking at your inflammation and liver markers to find or treat a medical problem, you will be 
told if they notice something unusual.  You and your regular doctor can decide together whether 
to follow up with more tests or treatment.  Because the inflammation and liver markers done in 
this study are not for medical purposes, the research results will not be sent to you or to your 
regular doctor. Your anonymous sample will be sent to coordinating research centers outside of 
UT Southwestern who are studying your disease. Your sample will be made anonymous by 
removing any identifiable information about you before it is shared with investigators outside of 
UT Southwestern.
Study Procedures by Study Day:
The procedures and evaluations are outlined below.
Screening:
Complete screening will occur once the informed consent has been obtained as described above. 
Individuals who are not eligible for the study will be given the option for the same follow-up without 
the study medicine. 
The study subject’s general health and study information include:

Signed consent

Other routine information including sex, date of birth, race and ethnic group (Hispanic or 
not).

Medicine history over the past 30 days, including prescribed and over-the-counter ones, 
herbal remedies, vitamins and minerals.

Alcohol in the past 60 days and for the years before.
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 4 of 8
DO NOT DISCLOSE

Drawing blood for blood counts, clotting, and chemistry tests for the liver, pancreas and 
kidneys; female study subjects will have a pregnancy test. These are standard tests for 
your condition. The total amount of blood for these tests is about 7 tablespoons.

Physical examination, including height, weight, and vital signs (blood pressure, pulse, 
breathing and temperature)

Imaging of the abdomen.
Assessments: 
Study day 0 

Record health history and review alcohol use.

Standard of care laboratory studies (chemistry, blood count, clotting, urine, infection 
including tuberculosis testing) 

Tests for fluid in belly, if it is there

Urine, blood (3 tablespoons) and stool testing for research.

Nutritional Assessment with a hand grip measurement.

Make a list of all medicines including those purchased over the counter, from health food 
stores and other remedies.

Check blood pressure, pulse, temperature and breathing (vital signs) and physical exam.
Procedures for storing of extra or left over samples
Samples of your blood and urine will be frozen and stored so that the researchers can test for 
any new inflammation or liver markers that are developed. 

Samples will be labeled with a study number, not with your name or other personal 
number. 

The key for study numbers will be kept in your medical record in a special section for 
research study information. 

The anonymous samples will be sent to Cleveland Clinic for storage

The Principal Investigators will decide where and how the remaining samples will be 
processed

Samples may be sent to other scientists for studies approved by their local IRB’s to 
further understand this disease.
What are the risks of the study?
Psychological Stress
Some of the questions we will ask you about your personal habits, as part of this study, may make 
you feel uncomfortable.  You may refuse to answer any of the questions, take a break or stop 
your participation in this study at any time.
Loss of Confidentiality
Any time information is collected; there is a potential risk for loss of confidentiality.  Every effort 
will be made to keep your information confidential; however, this cannot be guaranteed. 
Risks of Blood Drawing
Risks associated with drawing blood from your arm include minimal discomfort and/or bruising.  
Infection, excess bleeding, clotting, and/or fainting also are possible, although unlikely. You will 
have You will have 6 tablespoons of blood collected because you are in this research study, in 
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 5 of 8
DO NOT DISCLOSE
addition to the tests that you need to take care of your health (another 13 tbspns over the 6 
months).  
How will risks be minimized or prevented?  
Potential risks and discomforts will be minimized to the greatest extent possible by appropriate 
training of all researchers and study personnel, monitoring you closely, withdrawal from the study 
upon evidence of difficulty or an adverse event; referral for treatment, counseling or other 
necessary follow-up.
What will my responsibilities be during the study?  
While you are part of this study, the researchers will follow you closely to determine whether there 
are problems that need medical care.  It is your responsibility to do the following:

Ask questions about anything you do not understand.

Follow the researchers’ instructions.

Let the researchers know if your telephone number or address changes.
If I agree to take part in this research study, will I be told of any new risks that may be 
found during the course of the study?
Yes.  You will be told if any new information becomes available during the study that could cause 
you to change your mind about continuing to participate or that is important to your health or 
safety.
What should I do if I think I am having problems?
If you have unusual symptoms, pain, or any other problems while you are in the study, you should 
report them to the researchers right away.  Telephone numbers where they can be reached are 
listed on the first page of this consent form. If you have a sudden, serious problem, like difficulty 
breathing or severe pain, go to the nearest hospital emergency room, or call 911 (or the correct 
emergency telephone number in your area).  Tell emergency personnel about any medications 
you are taking, including any medications you are taking for this study.  
What are the possible benefits of this study?
If you agree to take part in this study, the researchers cannot guarantee that you will benefit from 
participation in this research. 
We hope the information learned from this study will benefit others with inflammation of the liver 
from alcohol.  Information gained from this research could lead to treatment with lower risks of 
dying in the first 6 months after being admitted to the hospital for hepatitis from alcohol.  
What options are available if I decide not to take part in this research study?
You do not have to participate in this research to receive care for your medical problem. 
Will I be paid if I take part in this research study?
There are no funds available to pay for parking expenses, transportation to and from the research 
center, lost time away from work etc., lost wages, or child care expenses.
Will my insurance provider or I be charged for the costs of any part of this research study?
No. Neither you, nor your insurance provider, will be charged for anything done only for this 
research study. However, the standard medical care for your condition (care you would have 
received whether or not you were in this study) is your responsibility (or the responsibility of your 
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 6 of 8
DO NOT DISCLOSE
insurance provider or governmental program).  You will be charged, in the standard manner, for 
any procedures performed for your standard medical care.
What will happen if I am harmed as a result of taking part in this study?
It is important that you report any illness or injury to the research team listed at the top of this form 
immediately. Compensation for an injury resulting from your participation in this research is not 
available from the University of Texas Southwestern Medical Center or Parkland Health & 
Hospital System. You retain your legal rights during your participation in this research
Can I stop taking part in this research study?
Yes.  If you decide to participate and later change your mind, you are free to stop taking part in 
the research study at any time. If you decide to stop taking part in this research study, it will not 
affect your relationship with the UT Southwestern staff or doctors.  Whether you participate or not 
will have no effect on your legal rights or the quality of your health care.
If I agree to take part in this research study, can I be removed from the study without my 
consent?
Yes.  The researchers may decide to take you off this study if:

The researchers believe that participation in the research is no longer safe for you.

You are unable to follow the researcher’s instructions.
Will my information be kept confidential?
Medical information collected during this study and the results of any test or procedure done may 
be included in your medical record and this information may be available to health care providers 
and authorized persons including your insurance company.
You should know that certain organizations that may look at and/or copy your medical records for 
research, quality assurance, and data analysis include:
•
Cleveland Clinic, University of Louisville, University of Massachusetts, NIH
•
Representatives of government agencies, like the U.S. Food and Drug Administration 
(FDA), involved in keeping research safe for people; and
•
The UT Southwestern Institutional Review Board. 
A description of this clinical trial will be available on http://www.clinicaltrials.gov, as required by 
the U.S. Law.  This Web site will not include information that can identify you.  At most, the Web 
site will include a summary of the results.  You can search this Web site at any time.
In addition to this consent form, you will be asked to sign an "Authorization for Use and Disclosure 
of Protected Health Information."  This authorization will give more details about how your 
information will be used for this research study, and who may see and/or get copies of your 
information.
Are there procedures I should follow after stopping participation in this research?
Yes.  If you, the researchers, or the sponsor stops your participation in the research, you may be 
asked to do the following:

Let the researchers know immediately that you wish to withdraw from the research.

Return to the research center for tests that may be needed for your safety.
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 7 of 8
DO NOT DISCLOSE

Discuss your future medical care, if any, with the researchers and/or your personal doctor.
Whom do I call if I have questions or problems?
For questions about the study, contact Dr. Mitchell at 214-648-4570 during regular business hours 
and at 214-648-3111 after hours and on weekends and holidays.  
For questions about your rights as a research participant, contact the UT Southwestern 
Institutional Review Board (IRB) Office at 214-648-3060.
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 8 of 8
DO NOT DISCLOSE
SIGNATURES:
YOU WILL BE GIVEN A COPY OF THIS CONSENT FORM TO KEEP.
Your signature below certifies the following:

You have read (or been read) the information provided above.

You have received answers to all of your questions and have been told who to call if you 
have any more questions.

You have freely decided to participate in this research.

You understand that you are not giving up any of your legal rights.

You understand that a copy of this signed consent document, information about this study 
and the results of any test or procedure done may be included in your medical record and 
this information may be available to health care providers and authorized persons 
including your insurance company.
__________________________________________________
Participant’s Name (printed)
__________________________________________________
Participant’s Signature
_______________
Date & Time
__________________________________________________
Name of person obtaining consent (printed)
__________________________________________________
Signature of person obtaining consent
________________
Date & Time
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 1 of 11
DO NOT DISCLOSE
The University of Texas Southwestern Medical Center at Dallas
Parkland Health & Hospital System
CONSENT TO PARTICIPATE IN RESEARCH
Title of Research:
Novel therapies in moderately severe alcoholic hepatitis
Funding Agency/Sponsor:
NIH (funded)
Study Doctors:
Mack Mitchell, M.D.
Lisa Casey, M.D.
Jennifer Cuthbert, M.D.
You may call these study doctors or research personnel during regular office hours at 214-648-4570.  At other 
times, you may call them at 214-648-3111 and tell them that you need to contact your study doctors. Have the 
study information with you when you call after hours so that the hospital operators know who to contact.
Instructions:
Please read this consent form carefully and take your time making a decision about whether to participate.  As 
the researchers discuss this consent form with you, please ask him/her to explain any words or information that 
you do not clearly understand.  The purpose of the study, risks, inconveniences, discomforts, and other important 
information about the study are listed below.  If you decide to participate, you will be given a copy of this form to 
keep.
Why is this study being done?
This study is being done to follow what happens to the liver in response to inflammation from alcohol by collecting 
and testing research samples. The research studies will not improve the health of your liver. 
Why is this considered research? 
This is a research study because the tests are not routine for patients with liver problems. 
The following definitions may help you understand this study: 

Standard medical care means the regular care you would receive from your personal doctor if you choose 
not to participate in this research.

Researcher means the study doctors and research personnel at the University of Texas Southwestern 
Medical Center at Dallas and its affiliated hospitals.
Why am I being asked to take part in this research study?
You are being asked to take part in this study because you have an inflamed liver (hepatitis) that your doctors’ 
think is from your body’s reaction to alcohol. 
Do I have to take part in this research study?”
No.  You have the right to choose whether you want to take part in this research study.  If you decide to participate 
and later change your mind, you are free to stop participation at any time. If you decide not to take part in this 
research study it will not change your legal rights or the quality of health care that you receive at this center.
How many people will take part in this study?
About 50 people will take part in the medication study at UT Southwestern or Parkland Health and Hospital 
System. This study also is taking place at a number of other medical facilities around the country. There will be 
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 2 of 11
DO NOT DISCLOSE
a total of 130 people participating in this research study throughout the United States. People who don’t want to 
take a medication can be part of the research by participating in the new tests. 
What is involved in the study?
If you volunteer to take part in this research study, you will be asked to sign this consent form and will have the 
following tests and procedures.  Some of the procedures may be part of your standard medical care, but others 
are being done solely for the purpose of this study.
Screening Procedures
To help decide if you qualify to be in this study, the researchers will ask you questions about your health, 
including medications you take, your diet and habits. They will also get information from your medical record. 
Procedures and Evaluations during the Research
All study subjects will receive the standard medical care used for patients with hepatitis from your body’s reaction 
to alcohol. This includes:
1.
A good diet while in the hospital and recommendations for what to eat at home
a.
Lots of fresh vegetables, fruits, chicken, fish
b.
Vitamins and other special nutrition if needed
2.
Help with avoiding alcohol in the future
a.
Counselors
b.
Psychologists
c.
Rehabilitation assistance
3.
Only take medications prescribed by your doctors. Do not take any medication or diet supplement or 
over-the-counter remedy without checking with a study doctor or nurse. Avoid all pain medicines that 
have high risk associated with them because of liver disease.
a.
Aspirin and over the counter medications like ibuprofen Motrin®, Aleve® can damage the kidneys 
with as little as one tablet
b.
Stronger pain medicines that contain codeine or a similar agent can cause confusion related to 
liver disease
c.
Acetaminophen (Tylenol®) can directly cause liver damage 
4.
Treatment for any complications that can occur
a.
Antibiotics for infections
b.
Treatment for diarrhea or constipation or nausea and vomiting if they occur
5.
Blood drawing to follow the changes in your liver. 
6.
Follow-up in the regular outpatient liver clinic, after you leave the hospital, until your liver has completely 
recovered. The number of visits depends on how quickly you get better. This is likely to be:
a.
1 week after leaving the hospital 
b.
1 – 2 visits in the next month 
c.
1 – 2 visits in the next 2 – 4 months, depending on how quickly you get well 
d.
A final clinic visit after 6 months 
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 3 of 11
DO NOT DISCLOSE
In addition, the following special, extra studies will be done for research purposes when you come into clinic:
Where
When
What
How
In 
hospital
First day of 
the study
Inflammation markers and liver markers will 
be measured.  These tests are done as part 
of the research on treatment for your 
condition.
Blood and urine for testing to see why alcohol 
caused your body to react in this way. These 
tests are done as part of the standard 
treatment for your condition. 
Research tests: 
Taking extra tubes of blood 
when you have regular blood 
tests 
(amount 
= 
3 
tablespoons). 
Collecting 
urine and stool in a container.
In 
hospital 
or in 
clinic
Day 7
Inflammation markers and liver markers will 
be measured.  These tests are done as part 
of the research on treatment for your 
condition.
Blood and urine for testing to see why alcohol 
caused your body to react in this way. These 
tests are done as part of the standard 
treatment for your condition. 
Research tests: 
Taking extra tubes of blood 
when you have regular blood 
tests 
(amount 
= 
2 
tablespoons). 
Collecting 
urine in a container.
In clinic
1 month
3 months
6 months
Inflammation markers and liver markers will 
be measured.  These tests are done as part 
of the research on treatment for your 
condition.
A blood test to see if your gut is leaky. This 
test is part of the research on treatment for 
your condition.
Blood and urine for testing to see why alcohol 
caused your body to react in this way. These 
tests are done as part of the standard 
treatment for your condition. 
Research tests: 
Taking extra tubes of blood 
when you have regular blood 
tests (amount = 3 
tablespoons). Collecting 
urine and stool in a 
container.
The inflammation and liver markers in this study are designed for research, not for medical purposes. They are 
not useful for finding problems or diseases.  Even though the researchers are not looking at your inflammation 
and liver markers to find or treat a medical problem, you will be told if they notice something unusual.  You and 
your regular doctor can decide together whether to follow up with more tests or treatment.  Because the 
inflammation and liver markers done in this study are not for medical purposes, the research results will not be 
sent to you or to your regular doctor. Your anonymous sample will be sent to coordinating research centers 
outside of UT Southwestern who are studying your disease. Your sample will be made anonymous by removing 
any identifiable information about you before it is shared with investigators outside of UT Southwestern.
Study Procedures by Study Day:
A summary of evaluations is located in the schedule of events table provided at the end of this section.  The 
procedures and evaluations are outlined below.
Screening:
Complete screening will occur once the informed consent has been obtained as described above. Individuals 
who are not eligible for the study will be given the option for the same follow-up without the study medicine. 
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 4 of 11
DO NOT DISCLOSE
The study subject’s general health and study information include:

Signed consent

Other routine information including sex, date of birth, race and ethnic group (Hispanic or not).

Medicine history over the past 30 days, including prescribed and over-the-counter ones, herbal remedies, 
vitamins and minerals.

Alcohol in the past 60 days and for the years before.

Drawing blood for blood counts, clotting, and chemistry tests for the liver, pancreas and kidneys; female 
study subjects will have a pregnancy test. These are standard tests for your condition. The total amount 
of blood for these tests is about 7 tablespoons.

Physical examination, including height, weight, and vital signs (blood pressure, pulse, breathing and 
temperature)

Imaging of the abdomen.
Assessments at baseline and during study : 
Study Procedures by Study Day:
A summary is in the table at the end of this section.  
Study day 0 – start (within 24 hours of study beginning) 

Record health history and review alcohol use.

Standard of care laboratory studies (chemistry, blood count, clotting, urine, infection including 
tuberculosis testing) 

Tests for fluid in belly, if it is there

Urine, blood (3 tablespoons) and stool testing for research.

Make a list of all medicines including those purchased over the counter, from health food stores and other 
remedies.

Nutritional Assessment with a hand grip measurement.

Check blood pressure, pulse, temperature and breathing (vital signs) and physical exam.
Study day 1 – time zero 

Standard blood tests for your condition (1 tablespoon)
Study day 2: 

Inpatient assessment to include:

Review health history for changes. 

List all medicines

Check vital signs and physical exam 

Research studies (urine and ½ tablespoon of blood).

24 hour urine collection.

Standard blood tests for your condition (1½ tablespoons)
Study days 3-6:

If study subject remains inpatient or has outpatient visit:

Review health history for changes. . 

List all medicines

Check vital signs and physical exam 

Standard blood tests for your condition (1 tablespoon)
Study day 7: 

Inpatient assessment or outpatient clinic visit to include:

Review health history for changes. Review alcohol intake. 

List all medicines
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 5 of 11
DO NOT DISCLOSE

Check vital signs and physical exam 

Research studies (urine and 1 tablespoon of blood).

Standard and research blood tests (2 tablespoons)

Nutritional Assessment with a hand grip measurement.
Study days 8-14:

If study subject remains inpatient or has outpatient visit:

Review health history for changes. Review alcohol intake. 

List all medicines

Check vital signs and physical exam 

Standard blood tests for your condition (1 tablespoon)
Study days 15-27:

If study subject remains inpatient or has a clinically indicated outpatient visit:

Review health history for changes. Review alcohol intake. 

List all medicines

Check vital signs and physical exam 

Stop taking the injection once a day

Standard blood tests for your condition (1 tablespoons)
Study day 28:

Inpatient assessment or outpatient clinic visit to include:

Review health history for changes. Review alcohol intake. 

List all medicines

Check vital signs and physical exam 

Research studies (urine and ½ tablespoon blood).

Standard and blood tests for your condition (1½ tablespoon)

Nutritional Assessment with a hand grip measurement.
Study day 29 to 2 months:

If study subject remains inpatient during this interval or completes clinically indicated outpatient visit 
during this time, the following data will be recorded:

Review health history for changes. Review alcohol intake. 

List all medicines

Check vital signs and physical exam 

Standard blood tests for your condition (1 tablespoons)
Study 3 months ± 2 weeks: 

Inpatient assessment or outpatient clinic visit to include:

Review health history for changes. Review alcohol intake. 

List all medicines

Check vital signs and physical exam 

Research studies (urine, stool and ½ tablespoon blood).

Standard blood tests for your condition (1½ tablespoon)
Study 4, 5 months ± 2 weeks:

If study subject remains inpatient or completes clinically indicated outpatient visit during this time, the 
following will be done:

Review health history for changes. Review alcohol intake. 

List all medicines

Check vital signs and physical exam 
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 6 of 11
DO NOT DISCLOSE

Standard blood tests for your condition (1 tablespoons)
Study 6 months ± 2 weeks: 

Complete abdominal ultrasound.

Inpatient assessment or outpatient clinic visit to include:

Review health history for changes. Review alcohol intake. 

List all medicines

Check vital signs and physical exam 

Research studies (urine, ½ tablespoon blood and stool).

Standard blood tests for your condition (1½ tablespoons)

Nutritional Assessment with a hand grip measurement.
Procedures for storing of extra or left over samples
Samples of your blood and urine will be frozen and stored so that the researchers can test for any new 
inflammation or liver markers that are developed. 

Samples will be labeled with a study number, not with your name or other personal number. 

The key for study numbers will be kept in your medical record in a special section for research study 
information. 

The anonymous samples will be sent to Cleveland Clinic for storage

The Principal Investigators will decide where and how the remaining samples will be processed

Samples may be sent to other scientists for studies approved by their local IRB’s to further understand 
this disease.
How long can I expect to be in this study?
The study is for a total of 6 months, first as an inpatient and then as an outpatient for a total of 6 months. You 
can choose to stop participating for any reason at any time.  However, if you decide to stop participating in the 
study, we encourage you to tell the researchers.  You will be asked if you are willing to complete some study 
termination tests. 
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 7 of 11
DO NOT DISCLOSE
Purpose
Test
Day 0
Day
2 – 6*
Day 7
Day
8 – 27*
Day 28
2 mos*
3 mos
4 mos*
5 mos*
6 mos
Standard
General health and liver questions
x
x
x
x
x
x
x
x
x
x
Questions about drinking alcohol
x
x
x
x
x
x
x
x
x
x
Physical exam
x
x
x
x
x
x
x
x
x
x
Blood
Liver tests
x
x
x
x
x
x
x
x
x
x
Tests of chemicals and kidneys
x
x
x
x
x
x
x
x
x
x
Blood count
x
x
x
x
x
x
x
x
x
x
Cholesterol test
x
x
Pancreas tests
x
Tests for viruses and bacteria
x
TB skin test
x
Urine
Urine tests
x
Poisons
x
Fluid
Belly fluid chemicals and infection
x
Stool
Infection tests
x
Imaging
Ultrasound of belly
x
x
Research
Gut leakiness
x
x
x
x
Zinc levels
x
x
x
x
Stool bacteria tests
x
x
x
Inflammation tests
x
x-day 2
x
x
x
x
* if clinically indicated
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 8 of 11
DO NOT DISCLOSE
What are the risks of the study?
Psychological Stress
Some of the questions we will ask you about your personal habits, as part of this study, may make 
you feel uncomfortable.  You may refuse to answer any of the questions, take a break or stop 
your participation in this study at any time.
Loss of Confidentiality
Any time information is collected; there is a potential risk for loss of confidentiality.  Every effort 
will be made to keep your information confidential; however, this cannot be guaranteed. 
Risks of Blood Drawing
Risks associated with drawing blood from your arm include minimal discomfort and/or bruising.  
Infection, excess bleeding, clotting, and/or fainting also are possible, although unlikely.  You will 
have 6 tablespoons of blood collected because you are in this research study, in addition to the 
tests that you need to take care of your health (another 13 tbspns over the 6 months).  
How will risks be minimized or prevented?  
Potential risks and discomforts will be minimized to the greatest extent possible by appropriate 
training of all researchers and study personnel, monitoring you closely, withdrawal from the study 
upon evidence of difficulty or an adverse event; referral for treatment, counseling or other 
necessary follow-up.
What will my responsibilities be during the study?  
While you are part of this study, the researchers will follow you closely to determine whether there 
are problems that need medical care.  It is your responsibility to do the following:

Ask questions about anything you do not understand.

Keep your appointments.

Follow the researchers’ instructions.

Let the researchers know if your telephone number or address changes.

Tell the researchers before you take any new medication, even if it is prescribed by 
another doctor for a different medical problem or something purchased over the counter.

Tell your regular doctor about your participation in this study.

Carry information about contacting the study doctors in your purse or wallet.

Report to the researchers any injury or illnesses while you are on study, even if you do 
not think they are related. 
If I agree to take part in this research study, will I be told of any new risks that may be 
found during the course of the study?
Yes.  You will be told if any new information becomes available during the study that could cause 
you to change your mind about continuing to participate or that is important to your health or 
safety.
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 9 of 11
DO NOT DISCLOSE
What should I do if I think I am having problems?
If you have unusual symptoms, pain, or any other problems while you are in the study, you should 
report them to the researchers right away.  Telephone numbers where they can be reached are 
listed on the first page of this consent form. If you have a sudden, serious problem, like difficulty 
breathing or severe pain, go to the nearest hospital emergency room, or call 911 (or the correct 
emergency telephone number in your area).  Tell emergency personnel about any medications 
you are taking.
What are the possible benefits of this study?
If you agree to take part in this study, there may be direct benefits to you.  The researchers cannot 
guarantee that you will benefit from participation in this research. 
We hope the information learned from this study will benefit others with inflammation of the liver 
from alcohol.  Information gained from this research could lead to treatment with lower risks of 
dying in the first 6 months after being admitted to the hospital for hepatitis from alcohol.  
What options are available if I decide not to take part in this research study?
You do not have to participate in this research to receive care for your medical problem. Instead 
of being in this study, you have the following option:

Being treated with standard medical care
Please talk to the researchers or your personal doctor about these options. 
Will I be paid if I take part in this research study?
There are no funds available to pay for parking expenses, transportation to and from the research 
center, lost time away from work etc., lost wages, or child care expenses.
Will my insurance provider or I be charged for the costs of any part of this research study?
No. Neither you, nor your insurance provider, will be charged for anything done only for this 
research study. However, the standard medical care for your condition (care you would have 
received whether or not you were in this study) is your responsibility (or the responsibility of your 
insurance provider or governmental program).  You will be charged, in the standard manner, for 
any procedures performed for your standard medical care.
What will happen if I am harmed as a result of taking part in this study?
It is important that you report any illness or injury to the research team listed at the top of this form 
immediately. Compensation for an injury resulting from your participation in this research is not 
available from the University of Texas Southwestern Medical Center or Parkland Health & 
Hospital System. You retain your legal rights during your participation in this research
Can I stop taking part in this research study?
Yes.  If you decide to participate and later change your mind, you are free to stop taking part in 
the research study at any time. If you decide to stop taking part in this research study, it will not 
affect your relationship with the UT Southwestern staff or doctors.  Whether you participate or not 
will have no effect on your legal rights or the quality of your health care.
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 10 of 11
DO NOT DISCLOSE
If I agree to take part in this research study, can I be removed from the study without my 
consent?
Yes.  The researchers may decide to take you off this study if:

The researchers believe that participation in the research is no longer safe for you.

You are unable to follow the researcher’s instructions.
Will my information be kept confidential?
Medical information collected during this study and the results of any test or procedure done may 
be included in your medical record and this information may be available to health care providers 
and authorized persons including your insurance company.
You should know that certain organizations that may look at and/or copy your medical records for 
research, quality assurance, and data analysis include:
•
Cleveland Clinic, University of Louisville, University of Massachusetts, NIH
•
Representatives of government agencies, like the U.S. Food and Drug Administration 
(FDA), involved in keeping research safe for people; and
•
The UT Southwestern Institutional Review Board. 
A description of this clinical trial will be available on http://www.clinicaltrials.gov, as required by 
the U.S. Law.  This Web site will not include information that can identify you.  At most, the Web 
site will include a summary of the results.  You can search this Web site at any time.
In addition to this consent form, you will be asked to sign an "Authorization for Use and Disclosure 
of Protected Health Information."  This authorization will give more details about how your 
information will be used for this research study, and who may see and/or get copies of your 
information.
Are there procedures I should follow after stopping participation in this research?
Yes.  If you, the researchers, or the sponsor stops your participation in the research, you may be 
asked to do the following:

Let the researchers know immediately that you wish to withdraw from the research.

Return to the research center for tests that may be needed for your safety.

Discuss your future medical care, if any, with the researchers and/or your personal doctor.
Study ID: STU 092012-012   Date Approved: 9/13/2017


Page 11 of 11
DO NOT DISCLOSE
Whom do I call if I have questions or problems?
For questions about the study, contact Dr. Mitchell at 214-648-4570 during regular business hours 
and at 214-648-3111 after hours and on weekends and holidays.  
For questions about your rights as a research participant, contact the UT Southwestern 
Institutional Review Board (IRB) Office at 214-648-3060.
SIGNATURES:
YOU WILL BE GIVEN A COPY OF THIS CONSENT FORM TO KEEP.
Your signature below certifies the following:

You have read (or been read) the information provided above.

You have received answers to all of your questions and have been told who to call if you 
have any more questions.

You have freely decided to participate in this research.

You understand that you are not giving up any of your legal rights.

You understand that a copy of this signed consent document, information about this study 
and the results of any test or procedure done may be included in your medical record and 
this information may be available to health care providers and authorized persons 
including your insurance company.
__________________________________________________
Participant’s Name (printed)
__________________________________________________
Participant’s Signature
_______________
Date & Time
__________________________________________________
Name of person obtaining consent (printed)
__________________________________________________
Signature of person obtaining consent
________________
Date & Time
Study ID: STU 092012-012   Date Approved: 9/13/2017