Metabolic Effects of Metformin Therapy in Obstructive Sleep Apnea
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Changes in Matsuda Index
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 35 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Metformin + PAP (Drug)
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.
干预措施: Placebo oral capsule + PAP (Drug)
结局指标
主要结局
Changes in Matsuda Index
时间窗: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.
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.
次要结局
- 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 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 Disposition Index(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 Homeostasis Model Assessment for Insulin Resistance (HOMA-IR)(approximately 4 months, includes measures obtained at baseline and 3 month follow-up.)
研究者
Prachi Singh
Associate Professor
Pennington Biomedical Research Center