A Study to Evaluate the Effect of Aleglitazar on Cardiac Energetics and Function in Patients With Type 2 Diabetes Mellitus and no History of Coronary Artery Disease

Study Overview
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Brief Summary
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A single center, double-blind, placebo-controlled, randomized, crossover, phase II study to assess the effect of aleglitazar on cardiac energetics and function in patients with uncomplicated type 2 diabetes mellitus and no history of coronary artery disease who are drug-naïve or treated with stable metformin. Eligible patients will receive either 150 mcg aleglitazar or placebo orally daily for 6 weeks. After a washout period of 6 weeks, patients will cross over to the treatment not yet received.

Official Title
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A SINGLE CENTER, DOUBLE-BLIND, PLACEBO-CONTROLLED, RANDOMIZED, CROSSOVER, PHASE II STUDY TO ASSESS THE EFFECT OF ALEGLITAZAR ON CARDIAC ENERGETICS AND FUNCTION IN PATIENTS WITH UNCOMPLICATED TYPE 2 DIABETES MELLITUS AND NO HISTORY OF CORONARY ARTERY DISEASE WHO ARE DRUG-NAÏVE OR TREATED WITH STABLE METFORMIN MONOTHERAPY

Conditions
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Diabetes Mellitus Type 2

Intervention / Treatment
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* Drug: aleglitazar
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, 40 to 70 years of age (inclusive) at screening Patients with Type 2 diabetes mellitus diagnosed at least 12 weeks before screening and either drug-naïve or treated with stable metformin monotherapy for at least 12 weeks prior to screening HbA1c >/= 7 % and </= 9% at screening Absence of history of coronary artery disease Exclusion Criteria: Diagnosis or history of Type 1 diabetes mellitus, diabetes resulting from pancreatic injury, or secondary forms of diabetes Current treatment with fibrates, thiazolidinediones, or insulin Prior intolerance to thiazolidinediones and/or fibrates Clinically significant liver disease or impaired liver function Know chronic diabetic complications (i.e. retinopathy, neuropathy, nephropathy) Symptomatic congestive heart failure classified as NYHA class II-IV Diagnosed and/or treated malignancy within the past 5 years, except for treated basal cell skin cancer, in situ carcinoma of the cervix, or in situ prostate cancer Contraindications to MRI, or inability to tolerate MRI scanning

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aleglitazar<br> | Drug: aleglitazar<br>* 150 mcg orally daily, 6 weeks<br>|
| Placebo Comparator: Placebo<br> | Drug: placebo<br>* orally daily, 6 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac energetics: Change in PCr/ATP ratio using phosphorus magnetic resonance spectroscopy (MRS) |  | from baseline to Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in left ventricular diastolic function measured by mitral inflow, tissue Doppler Imaging and magnetic resonance imaging (MRI) |  | from baseline to Week 6 | 
| Change in cardiac/hepatic triglyceride content assessed my MRS |  | from baseline to Week 6 |