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Diabetes ComplicationsPhase 2NCT00529204

Effects Of Exenatide On Liver Biochemistry, Liver Histology And Lipid Metabolism In Patients With Fatty Liver Disease

A Phase 2 study testing exenatide in people with Diabetes Complications and Fatty Liver, run by University of California, Davis at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are common complications of type 2 diabetes and leading causes of liver disease in the US and Europe. The prevalence of NAFLD and NASH are expected to become a major cause of liver disease related deaths and liver transplantation. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Diabetes Complications, Fatty Liver
What is being tested?
exenatide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteUnited States
Study dates
Oct 2007to Feb 2010
Phase
Phase 2
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 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age >18 years, < 70 years, inclusive
  • Type 2 diabetes on stable doses of sulfonylurea and/or metformin
  • Body mass index > 35 kg/m2
  • Presumed diagnosis of NAFLD based upon
  • an ALT > 1.5 times the upper limit of reference range,
  • no evidence of other causes of liver disease and
  • ultrasound findings compatible with fatty liver

Who cannot join

  • Clinical signs of cirrhosis as evidenced by any of the following
  • spider angiomata,
  • splenomegaly,
  • ascites
  • jaundice
  • encephalopathy
Show all 18Show fewer
  • INR > 1.2
  • Platelet count < 100,000/ml
  • Serum albumin < 3.0 g/dL
  • Other liver disease including chronic viral hepatitis (B or C), alcohol abuse, hemochromatosis, alpha-1 antitrypsin deficiency, autoimmune hepatitis, Wilson's disease, primary sclerosing cholangitis or primary biliary cirrhosis.
  • Current use of > 20 g of alcohol per day or unwillingness to avoid alcohol during the course of the study
  • Treatment with a thiazolidinedione or exenatide within 6 months of enrolling in the study
  • AST or ALT > 10 times the upper limit of normal
  • Treatment with any investigational drug within 4 weeks of enrollment
  • Pre-menopausal, fertile women unwilling to use contraceptives during the study period.
  • Pregnancy or lactation
  • Initiation or change in dose of hypolipidemic drugs (statins, niacin, cholestyramine are allowed) within 6 months of enrollment
  • Use of anticoagulation, bleeding disorders or other contraindications to liver biopsy

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of California Davis Medical Center

    Sacramento, California, 95817

Other trials in United States

About this study

Official title: Effects Of Exenatide (Byetta®) On Liver Biochemistry, Liver Histology And Lipid Metabolism In Patients With Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are common complications of type 2 diabetes and leading causes of liver disease in the US and Europe. The prevalence of NAFLD and NASH are expected to become a major cause of liver disease related deaths and liver transplantation. Currently, there are no specific therapies that alter the natural history of NAFLD.Preliminary evidence suggests that exenatide (Byetta®) may have several beneficial direct and indirect effects on NAFLD and liver lipid metabolism.

Read the detailed description

Preliminary evidence suggests that exenatide (Byetta®) may have several beneficial direct and indirect effects on NAFLD and liver lipid metabolism. Ad hoc analysis of phase III studies has shown that exenatide treatment is associated with improvement and normalization of alanine aminotransferase (ALT), a marker of liver injury, and that this effect is most pronounced in those with the greatest weight loss. In addition, treatment of leptin deficient ob/ob mice with exenatide reduced weight, liver lipid content, serum ALT and liver lipid peroxidation. Additional evidence suggests that the effects of exenatide on the liver are not simply a result of weight loss, but rather due to direct effects on the liver. Hepatocytes express GLP-1 receptors that are responsive to both GLP-1 and exenatide. Furthermore, exenatide treatment of ob/ob mice or isolated hepatocytes reduces mRNA for stearoyl-CoA desaturase-1 (SCD-1) and SREBP-1c, which would be expected to reduce DNL.

Based upon this data, we hypothesize that exenatide treatment of diabetic patients with NAFLD and NASH will reduce liver injury through multiple mechanisms including weight reduction associated with exenatide, improved lipid metabolism by decreased expression of hepatic genes involved in DNL and reduction of adipokines and cytokines associated with severe NASH. This study is aimed to address the potential safety and efficacy of exenatide in the treatment of NAFLD and test these hypotheses.

This will be an open label, single-arm, non-comparative trial of 20 patients with type 2 diabetes and NAFLD treated with exenatide for 6 months with the following specific aims to be assessed:

Determine the safety and efficacy of 24 weeks of exenatide treatment in diabetic patients with Non-Alcoholic Fatty Liver Disease (NAFLD) Efficacy will be measured by changes in serum ALT (primary endpoint) and liver histology.

Characterize the effects of exenatide on serum levels of adipokines and inflammatory cytokines including adiponectin, leptin and TNF- in NAFLD patients.

Compare the hepatic expression of SCD1, SREBP-1c and PPAR- mRNA in NAFLD patients pre- and post-treatment with exenatide.

Establish the effects of exenatide on post-prandial lipid metabolism.

Determine the effects of exenatide on liver fibrosis in NAFLD.

Being tested
exenatide
Keywords
Fatty Liver, Nonalcoholic fatty liver disease, NAFDL, Diabetes, ALT, exenatide
Medical subject headings
Diabetes Complications, Fatty Liver, Non-alcoholic Fatty Liver Disease, Diabetes Mellitus

What participants receive

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

  • exenatideDrug

    Also called BYETTA

    Subjects meeting the inclusion criteria will be treated with exenatide 5 µg BID s.c. for 3-7 days, followed by 10 µg BID s.c. daily to week 24

Study groups in NCT00529204
Study groupRoleWhat they receive
ExenatideExperimentalexenatide 5 µg BID s.c. daily for 28 days, followed by 10 µg BID s.c. daily from day 29 to week 24
Receives: Drug: exenatide

What is being measured

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

  1. Reduction in Serum ALT From Baseline to 24 Weeks of Exenatide Therapy

    Measured: 24 weeks

Secondary outcomes (2)

  1. Changes in Components of Liver Histology at Baseline and Week 24 Including Steatosis, Inflammation and Fibrosis

    Steatosis was grades on a scale of 0 (< 5%); 1 (5%- 33%); 2 (> 33% - 66%); and 3 (> 66%).

    Inflammation was graded on a scale of 0 (No foci); 1 (< 2 foci per 200 X field); 2 (2-4 foci per 200 X field); and 3 (>4 foci per 200 X field) Fibrosis was graded on a scale of 0 (None); 1 (Mild periportal or perisinusoidal); 2 (Moderate periportal or perisinusoidal); 3 (Bridging fibrosis); and 4 (cirrhosis)

    Measured: 24 weeks

  2. Safety of Exenatide in Patients With NAFLD and Type 2 Diabetes

    Measured: 24 weeks

Timeline

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

  1. First posted14 Sep 2007 (estimated)
  2. Study startOct 2007
  3. Primary completionJul 2009
  4. Study completionFeb 2010

Why it stopped: Lack of recruitment

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00529204
Sponsor's protocol ID
200715325
Other IDs
H80-MC-X006
Status last verified
May 2017
First submitted
12 Sep 2007
Last updated
20 Jun 2017
Data monitoring committee
Yes

Publications

  • Buse JB, Klonoff DC, Nielsen LL, Guan X, Bowlus CL, Holcombe JH, Maggs DG, Wintle ME. Metabolic effects of two years of exenatide treatment on diabetes, obesity, and hepatic biomarkers in patients with type 2 diabetes: an interim analysis of data from the open-label, uncontrolled extension of three double-blind, placebo-controlled trials. Clin Ther. 2007 Jan;29(1):139-53. doi: 10.1016/j.clinthera.2007.01.015.

    PubMed 17379054

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing exenatide in people with Diabetes Complications and Fatty Liver, run by University of California, Davis at 1 site 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 7 inclusion and 18 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: stopped early, as of the sponsor's last update on 20 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 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.

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 22 Dec 2014). 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?

Reduction in Serum ALT From Baseline to 24 Weeks of Exenatide Therapy (time frame: 24 weeks). 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 NCT00529204, which also lists 1 linked publication.

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 20 Jun 2017.

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