Cardiovascular Effects of Metformin on Obesity

Cardiovascular Effects of Metformin on Obesity With Subclinical Myocardial Dysfunction

It has been shown that asymptomatic obese adolescents can demonstrate abnormal regional myocardial contraction, with preserved global cardiac function. Metformin has been shown to decrease cardiovascular mortality in patients with type 2 diabetes and insulin resistance, but the mechanism of cardiovascular protection is unknown.

The purpose of this study is to evaluate the reversibility of subclinical cardiovascular abnormalities in obese adolescents with insulin resistance after a six-month course of Metformin. The investigators hypothesized that the beneficial effects of Metformin will be progressive and sustained after six months of therapy.

Study Overview

• Status: Withdrawn
• Conditions: Insulin Resistance
• Intervention / Treatment: Drug: Metformin

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • UCSF, Radiology and Biomedical Imaging

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adolescents 12 to 17 years old under clinical care at the UCSF WATCH clinic
• Body mass index> 95th percentile for age and gender according to the Centers for Disease Control and Prevention 2000 growth charts for the United States
• Insulin resistant after 6 months of healthy diet and exercise
• Able to understand the assent form

Exclusion Criteria:

• Patients with known cardiac disease

• Patients with contraindications to metformin as listed below:

  • Renal disease or renal (serum creatinine levels ≥1.5 mg/dL for males, and ≥1.4 mg/dL for females;
  • Known hypersensitivity to Metformin;
  • Acute or chronic metabolic acidosis;

• Patients with contraindications to MRI including:

  • Cardiac pacemaker;
  • Claustrophobia;
  • Metallic foreign body in the eye,
  • Aneurysm clip in the brain
• Pregnancy;
• Patients who could not stay still for 30 minutes within the MRI scanner due to other reasons besides claustrophobia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metformin, Insulin Resistance, Cardiac Function,; Metformin Hydrochloride Tablets will be administered with a start dose of 500mg twice daily with meals.	Drug: Metformin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left Ventricular Circumferential Strain change after a six-month course of Metformin.	Circumferential strain will be measured by cardiac MRI before and after the treatment. Change in circumferential strain (measured as percentage from end-diastolic wall thickness) from baseline is the main outcome of this study. We hypothesize that abnormal baseline circumferential stain will increase and reach normal values after Metformin treatment. We hypothesized that the beneficial effects of Metformin will be progressive and sustained.	6 months

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: US Department of Veterans Affairs
• Investigators: Principal Investigator: Karen G Ordovas, MD, MAS, University of California, San Francisco; Study Director: David Saloner, PhD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Anticipated): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: April 22, 2013
• First Submitted That Met QC Criteria: July 24, 2013
• First Posted (Estimate): July 29, 2013

Study Record Updates

• Last Update Posted (Actual): December 11, 2018
• Last Update Submitted That Met QC Criteria: December 7, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Insulin Resistance; Metformin; Cardiac Function
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: MetforminMRI; Cardiac MRI Metformin; Metformin Cardiac MRI (Other Identifier: UCSF)