The Influence of Metformin on Chronic Heart Failure Clinical Course in Patients With Prediabetes

The Effect of Metformin on Clinical Course of Ischemic Etiology Chronic Heart Failure in Patients With Prediabetes: the Open-label Randomized Clinical Trial

It is well known fact, that prediabetes is a predictor of high cardiovascular mortality, increasing the risk of developing such adverse cardiovascular events as myocardial infarction, stroke and sudden cardiac death. The key pathogenetic link in development of carbohydrates metabolism disorders (CMD) is insulin resistance (IR), which is one of the crucial mechanisms for the development and progression of chronic heart failure (CHF). IR disrupts the functioning of the myocardium due to endothelial dysfunction, inflammation, oxidative stress, remodeling and impaired myocardial metabolism. In condition of a combination of CMD and CHF the reverse development of hyperglycemia is also difficult due to hyperactivation of neurohormonal systems - renin-angiotensin-aldosterone system, in particular.

So, drug therapy should neutralize the undesirable metabolic effects of hyperglycemia on the course of CHF, as well as prevent the development of micro- and macrovascular complications.

The study will investigate the ability of metformin to impact on clinical and laboratory (neurohormonal, lipid profiles, renal function) parameters of ischemic etiology heart failure patients with prediabetes, as well as their quality of life and prognosis (incidence of adverse cardiovascular events). These tests will be assessed at the beginning and repeated after one year. At the end of the study we will investigate the difference between lifestyle modification effect and metformin treatment.

The study is funded by Ministry of Education and Science of Kyrgyz Republic.

Study Overview

Detailed Description

This is a single centre trial designed to investigate the benefit, if any, of 12-month metformin 2000 mg/day treatment on clinical course of chronic heart failure in 78 patients with coronary artery disease and impaired glucose tolerance.

Participants will be seen in three occasions: screening, baseline randomization, 6 month, final 12 month, during which clinical and laboratory indicators will be assessed. There will also be three telephone visits at: month 1, month 3, month 9.

At a screening visit an initial history will be performed during following informed consent. Participants will undergo a laboratory, clinical and instrumental screening in Chronic Heart Failure department of National Centre of cardiology and Internal Medicine named after academician M.Mirrakhimov. Among with anthropologic and clinical data, prior to metformin administration, blood samples were evaluated.

Participants who meet all inclusion criteria will return for the randomization during hospitalization to either Metformin or Lifestyle modification alone.

After 6 months of observation safety indicators will be evaluated, as well as fasting and postprandial glucose, creatinine, ECG.

In the active arm, therapy will be metformin in an initial dose of 1000 mg/day (metformin 500 mg х2/day). Participants will continue on Metformin 500 mg x2/day for 2 weeks, following safety blood checks this dose will be increased to 2000 mg/day. If the higher dose cannot be tolerated it will be reduced to 1000 mg/day (or stopped if not tolerated).

The target dose of Metformin at 2000 mg/day was chosen based on previous study of metformin in nondiabetic heart failure patients with IR

Study Type

Interventional

Enrollment (Actual)

97

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Bishkek, Kyrgyzstan, 720001
        • National Centre of Cardiology and Internal Medicine named after academician M.Mirrakhimov

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Aged 18 years or over (not older 65 y.o)
  • Participant willing and able to give informed consent
  • Documented Coronary artery disease (CAD): either angio-graphically documented CAD or a previous history of myocardial infarction/angina.
  • Verified heart failure functional class III (Nt-proBNP levels, 6-min walking test)
  • Fasting insulin resistance ≥ 2.5 (HOMA-IR)
  • Receiving basic therapy for CAD and chronic heart failure (CHF)
  • Able (in the investigators opinion) and willing to comply with all study requirements

Exclusion Criteria:

  • Cognitive impairments
  • Type 1 or 2 Diabetes mellitus, antihyperglycemic therapy in anamnesis
  • Unstable course of CAD
  • Acute heart failure or CHF decompensation
  • Malignancy (receiving active treatment) or other life threatening disease
  • Renal dysfunction (stage 3B or worse)
  • Thyroid dysfunction
  • Pregnancy/lactating females
  • Any other reason considered inappropriate by a study physician
  • Participants who have participated in any other clinical trial within the previous 30 days

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: metformin
Metformin, 1000 mg b.i.d, 12 months
patients were divided into 2 groups: 1st group was on lifestyle modification (LSM), 2nd group on regimen "LSM+ metformin (1000 g b.i.d)" during 12 months
Active Comparator: lifestyle modification
Lifestyle modification Standard Principles
Lifestyle modification Standard Principles

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with adverse events
Time Frame: 12 months
Safety and efficacy of Metformin will be determined by monitoring changes from randomization till the end of the study or so long the patient remains in the study , whichever is earlier
12 months
Number of participants with newly diagnosed diabetes mellitus
Time Frame: 12 months
Carbohydrate metabolism indicators will be determined by monitoring changes in fasting, postprandial glycemia and glycated hemoglobin
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Chronic heart failure patients Quality of Life
Time Frame: 12 months
Minnesota Living with Heart Failure Questionnaire will be evaluated at baseline and at 12 months
12 months
6-minute walking test results
Time Frame: 12 months
The test is based on measuring the walking distance with turns along a long corridor (≥30 m) at the patient's own pace. Results will be evaluated at baseline and at 12 months
12 months
Insulin resistance by HOMA-IR
Time Frame: 12 months
Improvement in insulin (insulin resistance by HOMA-IR) when treated with metformin compared to lifestyle modification in patients with ischemic etiology CHF and prediabetes using ELISA
12 months
Aldosterone levels
Time Frame: 12 months
Improvement in aldosterone levels when treated with metformin compared to lifestyle modification in patients with ischemic etiology CHF and prediabetes using ELISA
12 months
Nt-proBNP levels
Time Frame: 12 months
Improvement in Nt-proBNP levels when treated with metformin compared to lifestyle modification in patients with ischemic etiology CHF and prediabetes using ELISA
12 months
Renal function markers
Time Frame: 12 months
Creatinine levels with estimated glomerular filtration rate and daily proteinuria at a baseline and at 12 months to assess safety and influence of metformin
12 months
Lipid profile markers
Time Frame: 12 months
Improvement in lipid profile indicators (total cholesterol, high- and low-density lipoprotein cholesterol, triglycerides) when treated with metformin compared to lifestyle modification
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Akbay Sarybaev, National Centre of Cardiology and Internal Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2018

Primary Completion (Actual)

November 1, 2018

Study Completion (Actual)

November 15, 2019

Study Registration Dates

First Submitted

September 3, 2020

First Submitted That Met QC Criteria

September 11, 2020

First Posted (Actual)

September 16, 2020

Study Record Updates

Last Update Posted (Actual)

September 16, 2020

Last Update Submitted That Met QC Criteria

September 11, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Coronary Artery Disease

Clinical Trials on Metformin Hydrochloride

3
Subscribe