Metabolic Effects of Metformin Therapy in Obstructive Sleep Apnea

NCT ID: NCT04530747

Last Updated: 2023-01-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-28
• Study Completion Date: 2021-11-30

Brief Summary

The purpose of the study is to see if metformin improves metabolism in patients with obstructive sleep apnea (OSA) using positive airway pressure (PAP) therapy. Metformin is approved by the Food and Drug Administration (FDA) for the treatment and prevention of diabetes. It is not approved for use in patients with OSA.

Detailed Description

Positive airway pressure (PAP) is standard therapy for obstructive sleep apnea (OSA) but has shown mixed results for improvement of insulin sensitivity and does not reduce cardiovascular (CV) events and mortality, even in patients with established CV disease. Hence, eliminating intermittent hypoxia alone with standard PAP therapy may not be sufficient to restore metabolism. Additional adjunct strategies (such as metformin) known to improve metabolism may be required to reduce metabolic burden and CV risk in OSA patients. The aim of this study is to examine the longitudinal changes in metabolism of OSA patients receiving both PAP and metformin treatment.

The MET-OSA study will last about 4 months. After screening the participants to determine eligibility, baseline study measures will be obtained and the participants will be provided with standard PAP for OSA treatment. Participants will also be randomized to receive either placebo or metformin treatment for 3 months. Compliance to study drug will be determined during monthly follow-up visits. Final study visit will include assessment of all baseline study measures.

Conditions

Sleep Apnea, Obstructive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Metformin + PAP

Subjects randomized to this arm will be orally given 2000 mg metformin daily. Metformin dosage will be slowly increased to improve tolerance.

Subjects will also be provided PAP (positive airway pressure) device for standard management of obstructive sleep apnea.

Group Type: EXPERIMENTAL

Metformin + PAP

Intervention Type: DRUG

Subjects randomized to this arm will receive 500 mg capsules containing metformin extended release (XR). Metformin XR dosing will be 500 mg (1 x 500 mg) every evening (qPM) during Week 1, 1000 mg (2 x 500 mg) qPM during Week 2, 1500 mg (3 x 500 mg) qPM during Week 3, and 2000 mg (4 x 500 mg) qPM from Week 4 onwards.

Subjects will also be provided PAP (positive airway pressure) device for standard management of obstructive sleep apnea.

Placebo oral capsule + PAP

Subjects randomized to this arm will receive placebo matching study drug. Subjects will also be provided PAP (positive airway pressure) device for standard management of obstructive sleep apnea.

Group Type: PLACEBO_COMPARATOR

Placebo oral capsule + PAP

Intervention Type: DRUG

Subjects randomized to this arm will receive 500 mg capsules containing placebo. Placebo dosing will be 500 mg (1 x 500 mg) qPM during Week 1, 1000 mg (2 x 500 mg) qPM during Week 2, 1500 mg (3 x 500 mg) qPM during Week 3, and 2000 mg (4 x 500 mg) qPM from Week 4 onwards.

Subjects will also be provided PAP (positive airway pressure) device for standard management of obstructive sleep apnea.

Interventions

Metformin + PAP

Subjects randomized to this arm will receive 500 mg capsules containing metformin extended release (XR). Metformin XR dosing will be 500 mg (1 x 500 mg) every evening (qPM) during Week 1, 1000 mg (2 x 500 mg) qPM during Week 2, 1500 mg (3 x 500 mg) qPM during Week 3, and 2000 mg (4 x 500 mg) qPM from Week 4 onwards.

Subjects will also be provided PAP (positive airway pressure) device for standard management of obstructive sleep apnea.

Intervention Type: DRUG

Placebo oral capsule + PAP

Subjects randomized to this arm will receive 500 mg capsules containing placebo. Placebo dosing will be 500 mg (1 x 500 mg) qPM during Week 1, 1000 mg (2 x 500 mg) qPM during Week 2, 1500 mg (3 x 500 mg) qPM during Week 3, and 2000 mg (4 x 500 mg) qPM from Week 4 onwards.

Subjects will also be provided PAP (positive airway pressure) device for standard management of obstructive sleep apnea.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Body mass index (BMI) ≥ 30-50 kg/m^2 (inclusive).
• Apnea-Hypopnea Index ≥ 15 events/h.
• Must be able to provide written informed consent.
• Willing to participate and adhere to study procedures (video recorded in-lab sleep studies, positive airway pressure (PAP) treatment, take study drug, have adipose tissue and skeletal muscle biopsies).
• Women of child-bearing potential must agree to use appropriate contraception to avoid pregnancy throughout the study.
• Willing to have blood, as well as adipose and muscle tissue stored for future use.

Exclusion Criteria

• HbA1c > 6.4%.
• Severe or uncontrolled hypertension defined as systolic blood pressure (BP) ≥180 mmHg and/or diastolic BP ≥110 mmHg on the average of three seated measurements after being at rest for at least 5 minutes.
• Significant cardiovascular, hepatic, renal, neurologic, or psychiatric disease as determined by the study physician.
• Pregnancy, breast feeding or planning pregnancy in the coming 4 months.
• Impaired renal function defined as estimated glomerular filtration rate (eGFR) <60ml/min/1.73m2 (estimated with Chronic Kidney Disease Epidemiology Collaboration equation 1 method).
• Known hypersensitivity to metformin.
• Currently taking a glucose lowering or weight loss medications.
• Current PAP use or use of PAP in the past 6 months.
• Currently taking antihypertensive and lipid-lowering medications known to affect adipose tissue and skeletal muscle metabolism. For example, statins and drugs targeting renin-angiotensin system will not be allowed. However, use of diuretics, beta-blockers, alpha-blockers and calcium channel blockers may be allowed provided the participant is on a stable dose for at least 3 months prior to the study visit.
• Oxygen desaturation index <15 events/h of sleep.
• Any medication or condition that, in the opinion of the medical investigator, could interfere with the study outcomes or put the subject at risk by participating in the study.

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Pennington Biomedical Research Center

OTHER

Sponsor Role: lead

Responsible Party

Prachi Singh

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Prachi Singh, PhD

Role: PRINCIPAL_INVESTIGATOR

Pennington Biomedical Research Center

Locations

Recruiting core Pennington

Baton Rouge, Louisiana, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

P30DK072476

Identifier Type: NIH

Identifier Source: secondary_id

View Link

PBRC 2020-033

Identifier Type: -

Identifier Source: org_study_id