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Study of Liraglutide Versus Insulin on Liver Fat Fraction in Patients With Type 2 Diabetes (LIRAINS)

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ClinicalTrials.gov Identifier: NCT01399645
Recruitment Status : Completed
First Posted : July 22, 2011
Last Update Posted : August 27, 2014
Sponsor:
Collaborators:
Centre de Recherche du Centre Hospitalier de l'Université de Montréal
Diabetes Québec
Radiological Society of North America
Canadian Heads of Academic Radiology-GE Healthcare Development Award
Information provided by (Responsible Party):
Centre hospitalier de l'Université de Montréal (CHUM)

Tracking Information
First Submitted Date  ICMJE July 20, 2011
First Posted Date  ICMJE July 22, 2011
Last Update Posted Date August 27, 2014
Study Start Date  ICMJE May 2011
Actual Primary Completion Date June 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 21, 2011)
To determine liver fat fraction evolution induced by liraglutide and insulin [ Time Frame: 12 weeks ]
Improvement in liver steatosis defined by change in liver fat fraction as measured by MRI and MR spectroscopy at baseline and 12 weeks of treatment.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01399645 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Liraglutide Versus Insulin on Liver Fat Fraction in Patients With Type 2 Diabetes
Official Title  ICMJE Randomized Trial of Liraglutide and Insulin Therapy on Hepatic Steatosis as Measured by MRI and MRS in Metformin-treated Patients With Type 2 Diabetes: an Open Pilot Study
Brief Summary This study is conducted to test the hypothesis that in type 2 diabetic adults with fatty liver who are resistant to metformin, treatment with liraglutide in combination with metformin will cause an absolute reduction in liver fat superior to insulin-metformin treatment within a 3-month period, as measured by magnetic resonance imaging (MRI).
Detailed Description

Background: Non-alcoholic fatty liver disease (NAFLD) can now be identified in 70% of patients with type 2 diabetes. Insulin can be introduced at any point in the treatment of diabetes, but is potentially lipogenic. Preliminary studies have shown conflicting results on the impact of insulin on fatty liver.

Objectives: This study is conducted to test the hypothesis that in type 2 diabetic adults with NAFLD who are resistant to metformin, treatment with liraglutide in combination with metformin will cause an absolute reduction in liver fat superior to insulin-metformin treatment within a 3-month period, as measured by in vivo MRI and MRS.

Design: This will be a prospective, open label, randomized parallel trial to evaluate whether 12 weeks of treatment with a) liraglutide-metformin will improve steatosis in type 2 diabetic adults with NAFLD compared to treatment with b) insulin-metformin. Before and post-treatment MRI and MRS will be read blindly for quantification of steatosis. The primary outcome measure is defined as an improvement in steatosis of 5% before and after treatment between the 2 treatment groups.

Methods: Thirty-six patients will be randomized to either study group. After baseline metabolic measurements by blood sampling, transient ultrasound elastography, MRI and MRS, all subjects will be given metformin with a starting dose of 500 mg in one tablet twice daily. In addition, patients will be randomized to receive either liraglutide (0.6 - 1.8 mg subcutaneous per day ) or insulin glargine with an initial bedtime starting dose of 10 IU for a duration of 3 months.

Expected results: The results of this study will provide preliminary data for a large scale study comparing the 2 therapeutic regimen and establish the utility of MRI and MRS to monitor medical treatment in diabetic patients with fatty liver disease.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Nonalcoholic Fatty Liver Disease
  • Nonalcoholic Steatohepatitis
  • Type 2 Diabetes
Intervention  ICMJE Drug: Liraglutide-metformin vs insulin-metformin

Liraglutide (Victoza, Novo Nordisk) at a dose of 0.6 - 1.8 mg subcutaneous per day.

Insulin glargine (Lantus, Sanofi-Aventis) with an initial bedtime starting dose of 10 IU.

Other Names:
  • Liraglutide
  • Victoza
  • Insulin glargine
  • Lantus
Study Arms  ICMJE
  • Experimental: Liraglutide-Metformin

    Liraglutide (Victoza, Novo Nordisk) at a dose of 0.6 - 1.8 mg subcutaneous per day until the end of the study.

    All subjects will be given metformin with a starting dose of 500 mg in one tablet twice daily given before or during meals for the duration of the study.

    Intervention: Drug: Liraglutide-metformin vs insulin-metformin
  • Experimental: Insulin-Metformin

    Insulin glargine (Lantus, Sanofi-Aventis) with an initial bedtime starting dose of 10 IU. The patients will be taught to increase their insulin dose by 1 unit each day until achieving an FPG ≤ 7.0 mmol/L.

    All subjects will be given metformin with a starting dose of 500 mg in one tablet twice daily given before or during meals for the duration of the study.

    Intervention: Drug: Liraglutide-metformin vs insulin-metformin
Publications * Tang A, Rabasa-Lhoret R, Castel H, Wartelle-Bladou C, Gilbert G, Massicotte-Tisluck K, Chartrand G, Olivié D, Julien AS, de Guise J, Soulez G, Chiasson JL. Effects of Insulin Glargine and Liraglutide Therapy on Liver Fat as Measured by Magnetic Resonance in Patients With Type 2 Diabetes: A Randomized Trial. Diabetes Care. 2015 Jul;38(7):1339-46. doi: 10.2337/dc14-2548. Epub 2015 Mar 26.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 25, 2014)
35
Original Estimated Enrollment  ICMJE
 (submitted: July 21, 2011)
36
Actual Study Completion Date  ICMJE June 2014
Actual Primary Completion Date June 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Are 18 y.o. or older at screening (first visit),
  • Are ambulatory,
  • Are known for type 2 diabetes with criteria of failure of metformin monotherapy, metformin-sulfonylurea, metformin-repaglinide combined therapy defined as HbA1C ≥6.5,
  • Abdominal girth > 94 cm for men and > 80 cm for women,
  • Understand French or English instruction,
  • Able to comprehend and willingness to provide voluntary consent.

Exclusion Criteria:

  • Have any contra-indications for MRI (such as metallic implants, pacemaker or claustrophobia),
  • Have type 1 diabetes or have had episodes of ketoacidosis,
  • Have any major debilitating disease including malignant disorders,
  • Have had, within the last 6 months, evidence of significant heart disease or stroke, including myocardial infarction, unstable angina, coronary bypass and/or percutaneous transluminal coronary angioplasty (PTCA), congestive heart failure (New York Heart Association Class III-IV), or severe ischemic disease,
  • Patients having received insulin within 3 months prior to screening,
  • Have a serum creatine above >150 mmol/L or estimated GFR < 30 mL/min,
  • Women seeking pregnancy,
  • Have a history of chronic liver disease other than NAFLD, including HBV and HCV infection, hemochromatosis, Wilson's disease, alpha-1-antitrypsin deficiency, autoimmune hepatitis,
  • Current or previous use of oral or injectable corticosteroids,
  • Have excessive alcohol intake, defined as a daily limit of 30 g (3 drinks) for men and 20 g (2 drinks) for women.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01399645
Other Study ID Numbers  ICMJE CE09.159
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Centre hospitalier de l'Université de Montréal (CHUM)
Study Sponsor  ICMJE Centre hospitalier de l'Université de Montréal (CHUM)
Collaborators  ICMJE
  • Centre de Recherche du Centre Hospitalier de l'Université de Montréal
  • Diabetes Québec
  • Radiological Society of North America
  • Canadian Heads of Academic Radiology-GE Healthcare Development Award
Investigators  ICMJE
Principal Investigator: An Tang, MD Centre de Recherche du Centre Hospitalier de l'Université de Montréal
PRS Account Centre hospitalier de l'Université de Montréal (CHUM)
Verification Date August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP