Clinical trial NCT04530747: Metabolic Effects of Metformin Therapy in Obstructive Sleep Apnea
Official title: Metabolic Effects of Metformin Therapy in Obstructive Sleep Apnea
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Sleep Apnea, Obstructive
Keywords: Obstructive Sleep Apnea
Metformin
Lead sponsor: Pennington Biomedical Research Center
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2020-08-28
Enrollment: 16
Sex: ALL
Minimum age (years): 35
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Changes in Matsuda Index
timeFrame: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.
Secondary outcomes:
measure: Changes in Insulin Area Under the Curve (AUC) During 2-h Oral Glucose Tolerance Test (OGTT)
timeFrame: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.
measure: Changes in Glucose Area Under the Curve (AUC) During 2-h Oral Glucose Tolerance Test (OGTT)
timeFrame: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.
measure: Changes in Insulinogenic Index
timeFrame: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.
measure: Changes in Disposition Index
timeFrame: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.
measure: Changes in Homeostasis Model Assessment for Insulin Resistance (HOMA-IR)
timeFrame: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.
Other outcomes:
Locations:
city: Baton Rouge
country: United States
facility: Recruiting core Pennington
state: Louisiana
Study officials:
affiliation: Pennington Biomedical Research Center
name: Prachi Singh, PhD
role: PRINCIPAL_INVESTIGATOR
References: