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

This study has been completed.
Sponsor:
Collaborators:
Centre de Recherche du Centre Hospitalier de l'Université de Montréal
Diabete Quebec
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)
ClinicalTrials.gov Identifier:
NCT01399645
First received: July 20, 2011
Last updated: August 25, 2014
Last verified: August 2014
  Purpose

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).


Condition Intervention Phase
Nonalcoholic Fatty Liver Disease
Nonalcoholic Steatohepatitis
Type 2 Diabetes
Drug: Liraglutide-metformin vs insulin-metformin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Centre hospitalier de l'Université de Montréal (CHUM):

Primary Outcome Measures:
  • To determine liver fat fraction evolution induced by liraglutide and insulin [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 35
Study Start Date: May 2011
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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
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.

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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01399645

Locations
Canada, Quebec
Centre hospitalier de l'Université de Montréal
Montréal, Quebec, Canada, H2W 1T7
Sponsors and Collaborators
Centre hospitalier de l'Université de Montréal (CHUM)
Centre de Recherche du Centre Hospitalier de l'Université de Montréal
Diabete Quebec
Radiological Society of North America
Canadian Heads of Academic Radiology-GE Healthcare Development Award
Investigators
Principal Investigator: An Tang, MD Centre de Recherche du Centre Hospitalier de l'Université de Montréal
  More Information

No publications provided

Responsible Party: Centre hospitalier de l'Université de Montréal (CHUM)
ClinicalTrials.gov Identifier: NCT01399645     History of Changes
Other Study ID Numbers: CE09.159
Study First Received: July 20, 2011
Last Updated: August 25, 2014
Health Authority: Canada: Ethics Review Committee
Canada: Health Canada

Keywords provided by Centre hospitalier de l'Université de Montréal (CHUM):
Randomized trial
Open label
Pilot study
Single center

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Fatty Liver
Liver Diseases
Digestive System Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Glargine
Glucagon-Like Peptide 1
Insulin
Insulin, Globin Zinc
Liraglutide
Metformin
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Incretins
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014