NCT00650546

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
8

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Aug 2006

Typical duration for phase_2

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2006

Completed
1.7 years until next milestone

First Submitted

Initial submission to the registry

March 28, 2008

Completed
4 days until next milestone

First Posted

Study publicly available on registry

April 1, 2008

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2010

Completed
5.8 years until next milestone

Results Posted

Study results publicly available

May 12, 2016

Completed
Last Updated

April 11, 2017

Status Verified

March 1, 2017

Enrollment Period

4 years

First QC Date

March 28, 2008

Results QC Date

August 31, 2015

Last Update Submit

March 13, 2017

Conditions

Nonalcoholic Fatty Liver Disease

Keywords

Non-alcoholic steatohepatitisNASH

Outcome Measures

Primary Outcomes (2)

  • 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.

    between baseline and 24-28 weeks after initiating treatment

  • 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.

    Between baseline and 28 weeks of treatment with exenatide, sub q, 5-10 mcq.

Study Arms (1)

A pre treatment NAS score

EXPERIMENTAL

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

Drug: Exenatide

Interventions

ExenatideDRUG

5 mcg twice a day titrated to 10 mcg twice a day

Also known as: Byetta
A pre treatment NAS score

Eligibility Criteria

Age18 Years - 99 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Kansas City VA Medical Center

Kansas City, Missouri, United States

Location

Fort Sam Houston

San Antonio, Texas, United States

Location

Related Publications (11)

  • Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, Angulo P. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005 Jul;129(1):113-21. doi: 10.1053/j.gastro.2005.04.014.

    PMID: 16012941BACKGROUND

  • 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.

    PMID: 15017611BACKGROUND

  • 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.

    PMID: 12843147BACKGROUND

  • Promrat K, Lutchman G, Uwaifo GI, Freedman RJ, Soza A, Heller T, Doo E, Ghany M, Premkumar A, Park Y, Liang TJ, Yanovski JA, Kleiner DE, Hoofnagle JH. A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology. 2004 Jan;39(1):188-96. doi: 10.1002/hep.20012.

    PMID: 14752837BACKGROUND

  • Shadid S, Jensen MD. Effect of pioglitazone on biochemical indices of non-alcoholic fatty liver disease in upper body obesity. Clin Gastroenterol Hepatol. 2003 Sep;1(5):384-7. doi: 10.1053/s1542-3565(03)00198-8.

    PMID: 15017657BACKGROUND

  • Neuschwander-Tetri BA, Brunt EM, Wehmeier KR, Oliver D, Bacon BR. Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-gamma ligand rosiglitazone. Hepatology. 2003 Oct;38(4):1008-17. doi: 10.1053/jhep.2003.50420.

    PMID: 14512888BACKGROUND

  • Eng J, Andrews PC, Kleinman WA, Singh L, Raufman JP. Purification and structure of exendin-3, a new pancreatic secretagogue isolated from Heloderma horridum venom. J Biol Chem. 1990 Nov 25;265(33):20259-62.

    PMID: 1700785BACKGROUND

  • Eng J, Kleinman WA, Singh L, Singh G, Raufman JP. Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas. J Biol Chem. 1992 Apr 15;267(11):7402-5.

    PMID: 1313797BACKGROUND

  • Chen YE, Drucker DJ. Tissue-specific expression of unique mRNAs that encode proglucagon-derived peptides or exendin 4 in the lizard. J Biol Chem. 1997 Feb 14;272(7):4108-15. doi: 10.1074/jbc.272.7.4108.

    PMID: 9020121BACKGROUND

  • Greig NH, Holloway HW, De Ore KA, Jani D, Wang Y, Zhou J, Garant MJ, Egan JM. Once daily injection of exendin-4 to diabetic mice achieves long-term beneficial effects on blood glucose concentrations. Diabetologia. 1999 Jan;42(1):45-50. doi: 10.1007/s001250051111.

    PMID: 10027577BACKGROUND

  • Kenny PR, Brady DE, Torres DM, Ragozzino L, Chalasani N, Harrison SA. Exenatide in the treatment of diabetic patients with non-alcoholic steatohepatitis: a case series. Am J Gastroenterol. 2010 Dec;105(12):2707-9. doi: 10.1038/ajg.2010.363. No abstract available.

    PMID: 21131943RESULT

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Exenatide

Condition Hierarchy (Ancestors)

Fatty LiverLiver DiseasesDigestive System Diseases

Intervention Hierarchy (Ancestors)

PeptidesAmino Acids, Peptides, and ProteinsVenomsComplex MixturesToxins, BiologicalBiological Factors

Limitations and Caveats

As a case series our findings are limited by a control group and a small number of subjects enrolled. These limitations are tempered by the single expert hepatologist and the stringent definitions for histological improvement, ((primary end point)..

Results Point of Contact

Title
Patrick R Kenney, DO
Organization
Department of Gastroenterology, San Antonio Uniformed Services Health Consortium
pat.kenney@us.army.mil

Study Officials

  • Naga Chalasani, MD

    Indiana University School of Medicine

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
OTHER
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 28, 2008

First Posted

April 1, 2008

Study Start

August 1, 2006

Primary Completion

August 1, 2010

Study Completion

August 1, 2010

Last Updated

April 11, 2017

Results First Posted

May 12, 2016

Record last verified: 2017-03

Locations

US(3)