Impact of a Short-term Treatment With Canagliflozin (Canacardia-HF)

NCT03298009 | Withdrawn

• 1 other identifier: 28431754DIA4029
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

It is a mechanistic proof-of-concept study to demonstrate how SGLT-2 inhibitors (Canagliflozin) may have a beneficial role on cardiac energetic efficiency. Patients with type 2 diabetes and with HF diagnosed for at least 3 months will be selected. The participants will be randomized to a double-blind, crossover 2-week placebo vs. Cana 100 mg once daily, an interventional trial with a one-month washout period in between. At the term of the two-week placebo and canagliflozin treatment periods (visits 2 and 4), each participant will undergo an identical postprandial metabolic study with positron emission tomography (PET) and stable isotopic tracer methods.

Conditions

Type2 Diabetes; Heart Failure

Outcome Measures

Primary Outcomes (2)

• Change to be observed with canagliflozin on myocardial dietary fatty acid uptake

  will be assessed using oral administration of 18-fluoro-thiaheptadecanoic acid (\[18F\]-FTHA) with sequential dynamic. PET/CT scanning.

  3 months

• Change to be observed with canagliflozin on whole-body partitioning.

  will be assessed using oral administration of 18-fluoro-thiaheptadecanoic acid (\[18F\]-FTHA, with static PET/CT scanning

  3 months

Secondary Outcomes (3)

• myocardial and liver NEFA uptake

  3 months

• NEFA oxidative rate

  3 months

• plasma NEFA turnover

  1 year

Other Outcomes (6)

• Insulin sensitivity

  1 year

• Insulin secretion rate

  1 year

• β-cell function

  1 year

Study Arms (2)

Treatment 1

PLACEBO COMPARATOR

placebo oral capsule will be administered once daily, for 2 weeks

Drug: Placebo oral capsule; Radiation: PET imaging

Treatment 2

EXPERIMENTAL

Canagliflozine 100mg once daily, for 2 weeks

Drug: Canagliflozin 100mg; Radiation: PET imaging

Interventions

Canagliflozin 100mg DRUG

2-week intervention

Also known as: Invokana

Treatment 2

Placebo oral capsule DRUG

2-week intervention

Treatment 1

PET imaging RADIATION

1 day postprandial metabolic protocol at the end of treatment: CT scan followed by dynamic and pancorporel imaging

Treatment 1; Treatment 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HbA1c 7.5 -10.5%;
• LVEF \< 40%;
• NYHA class 2 or 3;
• NT pro-BNP level \> 600 pg/mL;
• Being on a stable-dose metformin therapy max 2500 mg/day or other hypoglycemic therapy and RAAS-blocking agents for at least 8 weeks;
• Being on optimal and stable-doses of heart failure medication including diuretics for at least 4 weeks;

You may not qualify if:

• age \<18 yo;
• NYHA class 4;
• Treatment with a fibrate or thiazolidinedione;
• Unstable or advanced renal failure;
• Unstable or new medical or surgical condition within the past 3 months;
• Heart failure caused by active inflammatory condition such as sarcoidosis or any form of myocarditis;
• History of diabetic ketoacidosis;
• Not on a stable regimen for at least 8 weeks before the screening visit;
• Female of child-bearing potential who is pregnant, breast feeding or intends to become pregnant or pre-menopausal female with a positive serum pregnancy test at the time of enrollment;
• Patients post bariatric surgery, or on weight loss medication;
• Contraindications to metformin, including allergy or intolerance;
• Hospitalization for heart failure within the 60 days prior to enrollment;
• Admission for an acute coronary syndrome, percutaneous coronary intervention, or cardiac surgery within the 60 days prior to enrollment;
• Planned cardiovascular revascularization (percutaneous intervention or surgical) or major cardiac surgery (coronary artery bypass grafting, valve replacement, ventricular assist device, cardiac transplantation, or any other surgery requiring thoracotomy) within the 90 days after enrollment;
• Patients who are volume depleted based upon physical examination at the time of enrollment;

Sponsors & Collaborators

• Université de Sherbrooke: lead
• Janssen Inc.: collaborator

MeSH Terms

Conditions

Heart Failure

Interventions

Canagliflozin; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glucosides; Glycosides; Carbohydrates; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• André C. Carpentier

  Université de Sherbrooke

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: tenured professor

Model Details: Placebo-controlled, double-blind, randomized crossover 2-week intervention study.

Study Record Dates

• First Submitted: September 26, 2017
• First Posted: September 29, 2017
• Study Start: May 1, 2018
• Primary Completion: June 30, 2018
• Study Completion: June 30, 2018
• Last Updated: December 13, 2024

Record last verified: 2024-12