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Role of Exenatide in NASH-a Pilot Study (NAFLD)

Primary Purpose

Nonalcoholic Fatty Liver Disease

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Exenatide
Sponsored by
Indiana University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Nonalcoholic Fatty Liver Disease focused on measuring Non-alcoholic steatohepatitis, NASH

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Well documented NASH based on clinical and histological criteria. Liver biopsy must have been obtained within 12-months prior to initiation of the study.
  • Subjects must have known diabetes (either diet controlled or only on Metformin or sulfonylureas such as glyburide or glipizide).
  • Subjects must be 18 year or older.

Exclusion Criteria:

  • Co-existing etiologies for chronic liver disease (hepatitis B or C, autoimmune or hemochromatosis, etc.).
  • Clinical or histological evidence of cirrhosis.
  • Alanine aminotransferase or aspartate aminotransferase > 300 IU/L.
  • Uncontrolled diabetes (hemoglobin A1C greater than or equal to 9%).
  • Insulin or TZD dependant DM.
  • Known human immunodeficiency virus infection.
  • Current or history of significant alcohol consumption within past 5 years. Significant alcohol consumption is defined as >20 grm/day in females and >30 grms/day in males or if alcohol consumption cannot satisfactorily be quantified.
  • Serum creatinine of greater than or equal to 2 mg/dl.
  • Active, serious medical disease (cardiac, renal, pulmonary, dermatologic, psychiatric illness) with likely life expectancy less 5 years.
  • Current or previous malignancy with expected life expectancy less than 5-years (other than basal cell cancer of the skin).
  • Use of drugs historically associated with NASH.
  • Histological evidence of malignancy, 4+ iron deposition, or any other type of liver disease.
  • Active substance abuse, such as alcohol,inhaled or injection drugs with the previous one year.
  • Known intolerance or allergy to exenatide (Byetta).
  • History of neuroglycopenia.
  • Women of childbearing potential must have had a negative pregnancy test prior to starting the study and should be willing to avoid pregnancy during the study period.
  • Women must not be nursing.

Sites / Locations

  • Indiana University
  • Kansas City VA Medical Center
  • Fort Sam Houston

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

A pre treatment NAS score

Arm Description

liver biopsy score pre treatment with exenatide 5 micrograms SQ (sub-cutaneous) twice a day titrated to 10 mcg SQ twice a day as tolerated

Outcomes

Primary Outcome Measures

Number of Patients With Improvement in Liver Histology After Treatment With Exenatide
Number of patients with liver histology improved with exenatide. The improvement of liver histology was defined as (1) no worsening of the fibrosis score, (11) improved score by at least one point in hepatocyte ballooning, and (111) either (a) improvement in NAS (NAFLD Activity Score) by two points spread across as least two of the three NAS components, or by (B)post-treatment NAS<3.
Change in NAS
The NAFLD Activity Score (NAS) is an underweight sum of steatosis (score 0-3), inflammation (score 0-3), ballooning scores (0-2). The NAS can range from 0-8 with the higher score indicating more aggressive disease.

Secondary Outcome Measures

Full Information

First Posted
March 28, 2008
Last Updated
March 13, 2017
Sponsor
Indiana University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT00650546
Brief Title
Role of Exenatide in NASH-a Pilot Study
Acronym
NAFLD
Official Title
Role of Exenatide in Treatment of NASH-a Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
August 2006 (undefined)
Primary Completion Date
August 2010 (Actual)
Study Completion Date
August 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Indiana University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
We hypothesize that exenatide (Byetta), a GLP-1 agonist administered subcutaneously for 24-28 weeks improves liver histology in diabetic patients with biopsy-proven NASH.
Detailed Description
Eight adult patients with known type 2 DM(Diabetic) and biopsy-proven NAFLD were treated with 5-10 mcg subcutaneous exenatide for 28 weeks. Liver histology was assessed using the NAFLD Activity Score (NAS) prior to therapy and after 28 weeks of therapy. We used the following criteria to define our primary outcome: (i) no worsening of fibrosis score, (ii) improved score by at least one point in hepatocyte ballooning, (iii) either (a) improvement in NAS by 2 or more points spread across at least two of the three NAS components, or (b) post-treatment NAS equal or greater than 3.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nonalcoholic Fatty Liver Disease
Keywords
Non-alcoholic steatohepatitis, NASH

7. Study Design

Primary Purpose
Other
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A pre treatment NAS score
Arm Type
Experimental
Arm Description
liver biopsy score pre treatment with exenatide 5 micrograms SQ (sub-cutaneous) twice a day titrated to 10 mcg SQ twice a day as tolerated
Intervention Type
Drug
Intervention Name(s)
Exenatide
Other Intervention Name(s)
Byetta
Intervention Description
5 mcg twice a day titrated to 10 mcg twice a day
Primary Outcome Measure Information:
Title
Number of Patients With Improvement in Liver Histology After Treatment With Exenatide
Description
Number of patients with liver histology improved with exenatide. The improvement of liver histology was defined as (1) no worsening of the fibrosis score, (11) improved score by at least one point in hepatocyte ballooning, and (111) either (a) improvement in NAS (NAFLD Activity Score) by two points spread across as least two of the three NAS components, or by (B)post-treatment NAS<3.
Time Frame
between baseline and 24-28 weeks after initiating treatment
Title
Change in NAS
Description
The NAFLD Activity Score (NAS) is an underweight sum of steatosis (score 0-3), inflammation (score 0-3), ballooning scores (0-2). The NAS can range from 0-8 with the higher score indicating more aggressive disease.
Time Frame
Between baseline and 28 weeks of treatment with exenatide, sub q, 5-10 mcq.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Well documented NASH based on clinical and histological criteria. Liver biopsy must have been obtained within 12-months prior to initiation of the study. Subjects must have known diabetes (either diet controlled or only on Metformin or sulfonylureas such as glyburide or glipizide). Subjects must be 18 year or older. Exclusion Criteria: Co-existing etiologies for chronic liver disease (hepatitis B or C, autoimmune or hemochromatosis, etc.). Clinical or histological evidence of cirrhosis. Alanine aminotransferase or aspartate aminotransferase > 300 IU/L. Uncontrolled diabetes (hemoglobin A1C greater than or equal to 9%). Insulin or TZD dependant DM. Known human immunodeficiency virus infection. Current or history of significant alcohol consumption within past 5 years. Significant alcohol consumption is defined as >20 grm/day in females and >30 grms/day in males or if alcohol consumption cannot satisfactorily be quantified. Serum creatinine of greater than or equal to 2 mg/dl. Active, serious medical disease (cardiac, renal, pulmonary, dermatologic, psychiatric illness) with likely life expectancy less 5 years. Current or previous malignancy with expected life expectancy less than 5-years (other than basal cell cancer of the skin). Use of drugs historically associated with NASH. Histological evidence of malignancy, 4+ iron deposition, or any other type of liver disease. Active substance abuse, such as alcohol,inhaled or injection drugs with the previous one year. Known intolerance or allergy to exenatide (Byetta). History of neuroglycopenia. Women of childbearing potential must have had a negative pregnancy test prior to starting the study and should be willing to avoid pregnancy during the study period. Women must not be nursing.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Naga Chalasani, MD
Organizational Affiliation
Indiana University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Kansas City VA Medical Center
City
Kansas City
State/Province
Missouri
Country
United States
Facility Name
Fort Sam Houston
City
San Antonio
State/Province
Texas
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
16012941
Citation
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Results Reference
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15017611
Citation
Younossi ZM, Gramlich T, Matteoni CA, Boparai N, McCullough AJ. Nonalcoholic fatty liver disease in patients with type 2 diabetes. Clin Gastroenterol Hepatol. 2004 Mar;2(3):262-5. doi: 10.1016/s1542-3565(04)00014-x. Erratum In: Clin Gastroenterol Hepatol. 2004 Jun;2(6):522.
Results Reference
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PubMed Identifier
12843147
Citation
Kolterman OG, Buse JB, Fineman MS, Gaines E, Heintz S, Bicsak TA, Taylor K, Kim D, Aisporna M, Wang Y, Baron AD. Synthetic exendin-4 (exenatide) significantly reduces postprandial and fasting plasma glucose in subjects with type 2 diabetes. J Clin Endocrinol Metab. 2003 Jul;88(7):3082-9. doi: 10.1210/jc.2002-021545.
Results Reference
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PubMed Identifier
14752837
Citation
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Results Reference
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PubMed Identifier
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Citation
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Results Reference
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PubMed Identifier
14512888
Citation
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Results Reference
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PubMed Identifier
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Citation
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Results Reference
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PubMed Identifier
1313797
Citation
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Results Reference
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PubMed Identifier
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Citation
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Results Reference
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PubMed Identifier
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Citation
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Results Reference
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PubMed Identifier
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Citation
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Results Reference
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