Nonalcoholic Fatty Liver DiseasePhase 2LIRAINSNCT01399645
Study of Liraglutide Versus Insulin on Liver Fat Fraction in Patients With Type 2 Diabetes
A Phase 2 study testing Liraglutide-metformin vs insulin-metformin in people with Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis, run by Centre hospitalier de l'Université de Montréal (CHUM) at 1 site in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Nonalcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis, Type 2 Diabetes
- What is being tested?
- Liraglutide-metformin vs insulin-metformin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteCanada
- Study dates
- May 2011to Jun 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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,
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- 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.
Trial locations and contacts
1 site in 1 country.
Canada1 site
Centre hospitalier de l'Université de Montréal
Montreal, Quebec, H2W 1T7
About this study
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
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).
Read the 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.
- Being tested
- Liraglutide-metformin vs insulin-metformin
- Keywords
- Randomized trial, Open label, Pilot study, Single center
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liraglutide-metformin vs insulin-metforminDrug
Also called Liraglutide, Victoza, Insulin glargine, Lantus
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.
| Study group | Role | What they receive |
|---|---|---|
| Liraglutide-Metformin | Experimental | 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. Receives: Drug: Liraglutide-metformin vs insulin-metformin |
| Insulin-Metformin | Experimental | 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. Receives: Drug: Liraglutide-metformin vs insulin-metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine liver fat fraction evolution induced by liraglutide and insulin
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.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2011 (estimated)
- Study startMay 2011
- Primary completionJun 2014
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Nonalcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- More trials run by Centre hospitalier de l'Université de Montréal (CHUM)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- 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
- Responsible party
- Sponsor
- Investigators
- An Tang, MD, Principal investigator, Centre de Recherche du Centre Hospitalier de l'Université de Montréal
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01399645
- Sponsor's protocol ID
- CE09.159
- Acronym
- LIRAINS
- Status last verified
- Aug 2014
- First submitted
- 20 Jul 2011
- Last updated
- 27 Aug 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Tang A, Rabasa-Lhoret R, Castel H, Wartelle-Bladou C, Gilbert G, Massicotte-Tisluck K, Chartrand G, Olivie 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.
PubMed 25813773
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01399645
- Acronym / sponsor ID
- LIRAINS / CE09.159
- Keywords
- Randomized trial, Open label, Pilot study, Single center
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Centre hospitalier de l'Université de Montréal (CHUM)University, hospital or other
- 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
- Study start
- May 2011
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 22 Jul 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Liraglutide-Metformin | Experimental | Drug: Liraglutide-metformin vs insulin-metforminLiraglutide (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. |
| Insulin-Metformin | Experimental | Drug: Liraglutide-metformin vs insulin-metforminInsulin 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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,
Key exclusion criteria (10 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Liraglutide-metformin vs insulin-metforminAlso: Liraglutide, Victoza, Insulin glargine, LantusLiraglutide (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. | Drug | Insulin-Metformin, Liraglutide-Metformin |
Primary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2014.
- Derived from this study: PubMed 25813773Tang A, Rabasa-Lhoret R, Castel H, Wartelle-Bladou C, Gilbert G, Massicotte-Tisluck K, Chartrand G, Olivie 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
An Tang, MD principal investigator
Centre de Recherche du Centre Hospitalier de l'Université de Montréal
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Liraglutide-metformin vs insulin-metformin in people with Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis, run by Centre hospitalier de l'Université de Montréal (CHUM) at 1 site in Canada.
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 6 inclusion and 10 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 27 Aug 2014. 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 Canada. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To determine liver fat fraction evolution induced by liraglutide and insulin (time frame: 12 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 NCT01399645, 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 27 Aug 2014.