Treatment of Diabetes in Patients With Systolic Heart Failure

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

Sponsors

Lead Sponsor: Virginia Commonwealth University

Collaborator: Janssen Scientific Affairs, LLC

Source Virginia Commonwealth University
Brief Summary

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

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.

Overall Status Completed
Start Date October 2016
Completion Date September 2018
Primary Completion Date September 2018
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
Change From Baseline Aerobic Exercise Capacity at 12 Weeks baseline and 12 weeks
Change From Baseline Ventilatory Efficiency at 12 Weeks baseline and 12 weeks
Enrollment 36
Condition
Intervention

Intervention Type: Drug

Intervention Name: Canagliflozin

Arm Group Label: Canagliflozin

Other Name: Invokana

Intervention Type: Drug

Intervention Name: Sitagliptin

Arm Group Label: Sitagliptin

Other Name: Januvia

Eligibility

Criteria:

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Antonio Abbate, MD, PhD Principal Investigator Virginia Commonwealth University
Location
Facility: Virginia Commonwealth University
Location Countries

United States

Verification Date

October 2019

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Canagliflozin

Type: Active Comparator

Description: Canagliflozin will be administered orally in pill form at 100 mg, daily for 12 weeks.

Label: Sitagliptin

Type: Active Comparator

Description: Sitagliptin will be administered orally in pill form at 100 mg, daily for 12 weeks.

Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Triple (Participant, Care Provider, Investigator)

Source: ClinicalTrials.gov