SGLT-2 Inhibitor and Myocardial Perfusion, Function and Metabolism in T2 DM Patients at High Cardiovascular Risk

NCT03151343 | Completed Phase 3

• 2 other identifiers: 2016-7752016-003743-10
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with type 2 diabetes (T2 DM) have a markedly increased risk of heart disease and it is estimated that, in the danish population, up 80% percent of patients with type 2 diabetes die from heart disease. The sodium glucose cotransport-2 (SGLT-2) inhibitors were developed as an anti-diabetic therapy reducing blood glucose and weight by decreasing glucose reabsorption in the kidneys, leading to glucose excretion via the urine. However, in 2015 the EMPA-REG study showed that treatment with the SGLT-2 inhibitor empagliflozin significantly reduced the cardiovascular mortality and risk of admission under the diagnosis of heart failure in a population of patients with type 2 diabetes in addition to other risk factors for heart disease. The mechanism behind this surprising result is unknown and warrants further study. The primary hypothesis of the present study is that treatment with empagliflozin improves the function and blood supply of the heart muscle cells in patients with type 2 diabetes and high risk of heart disease. The investigators will test this hypothesis by enrolling 92 participants with type 2 diabetes and other risk factors for heart disease, and treating them with either empagliflozin or a placebo. During the study period the investigators will monitor the effects of the treatment with various techniques such as heart scans using CT and ultrasound, measurements of the fluid pressures in the heart chambers, body composition measurements and a variety of relevant blood test.

Conditions

Type2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (2)

• Rb-82 PET

  Between group difference in the change in myocardial flow reserve (MFR) by Rb-82 PET. Measured as change in global perfusion from rest to adenosine-induced stress.

  13 weeks

• Invasive hemodynamics

  Substudy, performed on 38 participants from the main group. Using right heart catheterisation to measure between group difference in the change in pulmonary capillary weight pressure (PCWP) at 25 watts (supine bicycle ergometer)

  13 weeks

Secondary Outcomes (20)

• Echocardiography

  13 weeks

• GFR

  13 weeks

• U-alb/crea

  13 weeks

• 24 hour BP

  13 weeks

• Pulse wave analysis

  13 weeks

Study Arms (2)

Empagliflozin

EXPERIMENTAL

Empagliflozin, coated tablets, 25mg, once daily, for 13 weeks

Drug: Empagliflozin

Placebo

PLACEBO COMPARATOR

Placebo, coated tablets, once daily, for 13 weeks

Drug: Placebo Oral Tablet

Interventions

Empagliflozin DRUG

Empagliflozin tablet

Also known as: Jardiance

Empagliflozin

Placebo Oral Tablet DRUG

Sugar pill, visually identical to active comparator

Placebo

Eligibility Criteria

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

You may qualify if:

• A diagnosis of type 2 diabetes mellitus at least 3 months prior to baseline visit
• For patients on background therapy: stable dose of anti-diabetics within 30 days prior to baseline
• HbA1c of ≥6.5% and ≤10% at screening for patients on background therapy or HbA1c of ≥6.5 % and ≤ 9.0% at screening for drug-naïve patients.
• BMI ≤ 45 kg/m2 at screening
• Age ≥18 years
• Negative pregnancy test (fertile women). Fertile women must use safe contraceptives (spiral, hormonal contraceptives) for the duration of the study
• Able to understand the written patient information and to give informed consent
• Patients must have high cardiovascular risk, defined as at least one of the following:
• Albuminuria ( albumin/creatinine ratio ≥ 30 mg/g or plasma NT-proBNP ≥ 70 pg/ml)
• Confirmed history of myocardial infarction (\>2 months prior to baseline)
• Heart failure according to the Framingham Heart Failure Criteria
• Or patient discharged from hospital with a documented diagnosis of unstable angina within 12 months prior to baseline
• Evidence of coronary artery disease by CAG in 1 or more major coronary arteries
• OR at least one of the following: a positive noninvasive stress test, or A positive stress echocardiography showing regional systolic wall motion abnormalities, or A positive scintigraphic test showing stress-induced ischemia,
• History of ischemic or haemorrhagic stroke (\>2 months prior to informed consent)

You may not qualify if:

• Allergic to the study medication
• Treatment with SGLT-2 inhibitor within 3 months prior to baseline
• Impaired kidney function, eGFR ≤ 30 ml/min
• Severe liver insufficiency (Child-Pugh class C)
• ECG showing malign ventricular arrhythmia or prolonged QT-interval (\>500ms)
• Untreated clinical significant heart valve disease
• Planned cardiac surgery or angioplasty within 3 months.
• Myocardial infarction (MI) ≤ 30 days prior to baseline
• Percutaneous coronary intervention (PCI) ≤ 4 weeks prior to baseline
• History of coronary artery bypass graft (CABG) ≤ 8 weeks prior to enrollment
• Prior history of heart transplantation
• Unstable angina, known severe left main coronary artery stenosis, severe heart failure, uncontrolled arrhythmias, symptomatic hypotension or severe hypertension (systolic blood pressure \< 90 or \> 180 mmHg, respectively), sick sinus syndrome or \> 1st degree atrioventricular block in the absence of a functioning pacemaker
• Requirement of emergent cardiac medical intervention or catheterization
• Treatment with theophylline, or theophylline containing medications
• History of known or suspected bronchoconstrictive or bronchospastic lung disease (e.g., asthma)

Sponsors & Collaborators

• Caroline M Kistorp: lead
• Danish Heart Foundation: collaborator
• Herlev and Gentofte Hospital: collaborator
• Rigshospitalet, Denmark: collaborator

Study Sites (1)

Herlev og Gentofte Hospital

Herlev, 2730, Denmark

Location

Related Publications (25)

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MeSH Terms

Interventions

empagliflozin

Study Officials

• Caroline M Kistorp, MD, PhD.

  Herlev og Gentofte Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Participants will be treated with either empagliflozin or placebo

Study Record Dates

• First Submitted: March 12, 2017
• First Posted: May 12, 2017
• Study Start: March 29, 2017
• Primary Completion: May 22, 2020
• Study Completion: May 22, 2020
• Last Updated: August 18, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)