Metabolic Effects of Metformin Therapy in Obstructive Sleep Apnea

NCT04530747 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: PBRC 2020-033P30DK072476
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Sleep Apnea, Obstructive

Keywords

Obstructive Sleep Apnea; Metformin

Outcome Measures

Primary Outcomes (1)

• Changes in Matsuda Index

  Comparison of change in Matsuda Index as determined by 2-h oral glucose tolerance test (OGTT). During OGTT, response to oral 75g glucose intake is determined by measuring insulin and glucose in timed samples obtained at -5, 10, 20, 30, 60, 90 and 120 min. Matsuda index is a commonly used composite index to estimate whole-body insulin sensitivity. Matsuda index is calculated as (10,000/ square root of \[fasting glucose X fasting insulin\] X \[mean OGTT glucose X mean OGTT insulin\]). Increase in scores reflect improvement in whole body insulin sensitivity.

  approximately 4 months, includes measures obtained at baseline and 3 month follow-up.

Secondary Outcomes (5)

• Changes in Insulin Area Under the Curve (AUC) During 2-h Oral Glucose Tolerance Test (OGTT)

  approximately 4 months, includes measures obtained at baseline and 3 month follow-up.

• Changes in Glucose Area Under the Curve (AUC) During 2-h Oral Glucose Tolerance Test (OGTT)

  approximately 4 months, includes measures obtained at baseline and 3 month follow-up.

• Changes in Insulinogenic Index

  approximately 4 months, includes measures obtained at baseline and 3 month follow-up.

• Changes in Disposition Index

  approximately 4 months, includes measures obtained at baseline and 3 month follow-up.

• Changes in Homeostasis Model Assessment for Insulin Resistance (HOMA-IR)

  approximately 4 months, includes measures obtained at baseline and 3 month follow-up.

Study Arms (2)

Metformin + PAP

EXPERIMENTAL

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.

Drug: Metformin + PAP

Placebo oral capsule + PAP

PLACEBO COMPARATOR

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.

Drug: Placebo oral capsule + PAP

Interventions

Metformin + PAP 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.

Metformin + PAP

Placebo oral capsule + PAP 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.

Placebo oral capsule + PAP

Eligibility Criteria

• Age: 35 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pennington Biomedical Research Center: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Recruiting core Pennington

Baton Rouge, Louisiana, 70808, United States

Location

MeSH Terms

Conditions

Sleep Apnea, Obstructive

Interventions

Metformin

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Limitations and Caveats

Early termination due to PAP recall.

Results Point of Contact

• Title: Prachi Singh
• Organization: Pennington Biomedical Research Center

prachi.singh@pbrc.edu

12257633151

Study Officials

• Prachi Singh, PhD

  Pennington Biomedical Research Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 25, 2020
• First Posted: August 28, 2020
• Study Start: January 28, 2021
• Primary Completion: November 30, 2021
• Study Completion: November 30, 2021
• Last Updated: January 19, 2023
• Results First Posted: January 19, 2023

Record last verified: 2022-12

Locations

US (1)