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Nonalcoholic Fatty Liver DiseasePhase 2/3NAFLDNCT00650546

Role of Exenatide in NASH-a Pilot Study

A Phase 2/3 study testing Exenatide in people with Nonalcoholic Fatty Liver Disease, run by Indiana University at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Nonalcoholic Fatty Liver Disease
What is being tested?
Exenatide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
3 sitesUnited States
Study dates
Aug 2006to Aug 2010
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 17Show fewer
  • 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.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Indiana University

    Indianapolis, Indiana, 46202

  • Kansas City VA Medical Center

    Kansas City, Missouri

  • Fort Sam Houston

    San Antonio, Texas

Other trials in United States

About this study

Official title: Role of Exenatide in Treatment of NASH-a Pilot Study

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.

Read the 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.

Being tested
Exenatide
Keywords
Non-alcoholic steatohepatitis, NASH
Medical subject headings
Non-alcoholic Fatty Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ExenatideDrug

    Also called Byetta

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

Study groups in NCT00650546
Study groupRoleWhat they receive
A pre treatment NAS scoreExperimentalliver biopsy score pre treatment with exenatide 5 micrograms SQ (sub-cutaneous) twice a day titrated to 10 mcg SQ twice a day as tolerated
Receives: Drug: Exenatide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: between baseline and 24-28 weeks after initiating treatment

  2. 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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Apr 2008 (estimated)
  2. Study startAug 2006
  3. Primary completionAug 2010
  4. Study completionAug 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00650546
Sponsor's protocol ID
DK61737
Other IDs
U01DK061737
Acronym
NAFLD
Status last verified
Mar 2017
First submitted
28 Mar 2008
Last updated
11 Apr 2017
Data monitoring committee
No

Publications

  • 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.

    PubMed 16012941

  • 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.

    PubMed 15017611

  • 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.

    PubMed 12843147

  • 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.

    PubMed 14752837

  • 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.

    PubMed 15017657

  • 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.

    PubMed 14512888

  • 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.

    PubMed 1700785

  • 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.

    PubMed 1313797

  • 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.

    PubMed 9020121

  • 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.

    PubMed 10027577

  • 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.

    PubMed 21131943

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Exenatide in people with Nonalcoholic Fatty Liver Disease, run by Indiana University at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients With Improvement in Liver Histology After Treatment With Exenatide (time frame: between baseline and 24-28 weeks after initiating treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00650546, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2017.

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