Treatment of Diabetes in Patients With Systolic Heart Failure

Study Overview
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Brief Summary
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Investigator Initiated Study to study the effects of Canagliflozin 100 milligrams (mg) vs Sitagliptin 100 mg on parameters of aerobic exercise capacity (peak oxygen consumption [VO2]) and ventilator efficiency (minute ventilation [VE]/carbon dioxide production [VCO2] slope) at cardiopulmonary exercise test (CPET) after 12 weeks of active treatment (primary endpoints). Blood pressure (BP), body water content, body composition, cardiac function, and diet will be also measured (secondary endpoints).

Detailed Description
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Investigator Initiated Study: Randomized, double-blinded, active-control clinical trial to determine the safety and efficacy of Canagliflozin and Sitagliptin in patients with type 2 diabetes and systolic heart failure (HF). The investigators propose to study the effects of Canagliflozin 100 mg vs Sitagliptin 100 mg (both administered once daily for 12 weeks) on parameters of aerobic exercise capacity and ventilator efficiency by CPET after 12 weeks of active treatment. BP, body water content (Bioelectrical Impedance Analysis [BIA]), body composition (Dual-energy X-ray absorptiometry [DEXA]), cardiac function, diet and biomarkers will be also measured. Subjects with evidence of left ventricular hypertrophy will undergo cardiac magnetic resonance (CMR) imaging.

Official Title
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A Randomized Active-Control Double-Blinded Study to Evaluate the Treatment of Diabetes in Patients With Systolic Heart Failure

Conditions
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Heart Failure, Systolic, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Canagliflozin
* Drug: Sitagliptin


Participation Criteria
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Eligibility Criteria
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Major Inclusion Criteria: Symptomatic stable heart failure (New York Heart Association (NYHA) functional classification II-III) with reduced left ventricular ejection fraction (LVEF) ≤40% Peak exercise limited by shortness of breath and associated with a respiratory exchange ratio (RER) >1.00 (reflecting maximal aerobic effort); Poorly controlled Type 2 Diabetes Mellitus (T2DM)(HbA1c levels between 7.0% and 10.0% if on a treatment regimen including insulin, or between 6.5% and 10.0% if not on an insulin regimen); Eighteen years of age or older. Major Exclusion Criteria: Type I diabetes; Open label treatment with Sodium-GLucose coTransporter (SGLT)-2 inhibitors (within the past 3 months); Current treatment with thiazolidinedione (within the past 3 months); Chronic Renal Disease defined as Glomerular Filtration Rate (GFR) <50 ml•min-1/1.73m2 according to local laboratory Pregnancy or of child-bearing potential or lactating; Active or recent (within 2 weeks) genital/urinary infection; Concomitant conditions or treatment which would affect completion or interpretation of the study (i.e, physical inability to walk or run on a treadmill Inability to give informed consent. Exclusion criteria specific to the cardiac magnetic resonance (CMR) substudy. Estimated GFR <60 ml•min-1/1.73m2 Implantable cardioverter defibrillator, pacemaker or other implantable metal device not compatible with CMR scanning; Severe claustrophobia, inability to lay flat for up to 60 minutes, or other contraindication to CMR scanning.

Ages Eligible for Study
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Minimum Age: 18 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

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Canagliflozin<br>Canagliflozin will be administered orally in pill form at 100 mg, daily for 12 weeks. | Drug: Canagliflozin<br> <br> * Other names: Invokana;|
| Active Comparator: Sitagliptin<br>Sitagliptin will be administered orally in pill form at 100 mg, daily for 12 weeks. | Drug: Sitagliptin<br> <br> * Other names: Januvia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline Aerobic Exercise Capacity at 12 Weeks | Peak oxygen consumption (VO2) measured by maximal cardiopulmonary exercise test | baseline and 12 weeks | 
| Change From Baseline Ventilatory Efficiency at 12 Weeks | Minute ventilation (VE) relative to CO2 production (VCO2) slope measured by cardiopulmonary exercise test | baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Systolic Heart Failure, Canagliflozin, Sitagliptin Phosphate, Type 2 Diabetes, SGLT2 inhibitor, DPPIV inhibitor