A Phase 1/2 interventional study of Metformin + PAP and Placebo oral capsule + PAP in Sleep Apnea, Obstructive, sponsored by Pennington Biomedical Research Center. Terminated at 1 site in United States. Open to participants aged 35 Years to 65 Years. Per ClinicalTrials.gov, last updated 2023-01-19.
Sponsored by Pennington Biomedical Research Center · Phase 1/2, Interventional, and Prevention
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.
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.
1,423 studies on the registry are indexed under Apnea; 160 are open to participants now.
This study's enrollment of 16 is below the median of 51 across 966 interventional studies indexed under Apnea.
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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
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
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.
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.
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.
Time frame: 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)
Comparison of change in insulin AUC (area under the curve) as derived from 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. 2-h insulin AUC is calculated using trapezoid method. Higher AUC indicates higher insulin secretion.
Time frame: 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)
Comparison of change in glucose AUC (area under the curve) as derived from 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. 2-h glucose AUC is calculated using trapezoid method. Higher AUC indicates higher levels of circulating glucose.
Time frame: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.
Changes in Insulinogenic Index
Comparison of insulinogenic index derived from the initial 30 min data from the 2-h oral glucose tolerance test (OGTT). Insulinogenic index measures the early insulin response during the oral glucose challenge. The index is calculated as ratio of change in insulin to glucose from 0 to 30 min values derived from OGTT. Decrease in scores reflect improvement in insulin sensitivity.
Time frame: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.
Changes in Disposition Index
Comparison of change in disposition index as derived from 2-h oral glucose tolerance test. Disposition index measures beta-cell function and is calculated as product of Matsuda index and Insulinogenic index values. Increase in scores reflect improvement in glucose metabolism.
Time frame: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.
Changes in Homeostasis Model Assessment for Insulin Resistance (HOMA-IR)
Comparison of change in HOMA-IR value derived from fasting insulin and glucose. HOMA-IR is a simple index for insulin resistance based on fasting measures of glucose and insulin which is a commonly used end-point for assessment of insulin resistance in clinical trials. HOMA-IR is calculated as \[(fasting insulin X fasting glucose)/ 22.5\]. Higher values indicate higher insulin resistance. An increase will suggest a detrimental effect on glucose metabolism. Individuals with HOMA-IR \< 5.7% are considered healthy, between 5.7 and 6.4% are considered prediabetic, and more than 6.4% are considered diabetic.
Time frame: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.
| Milestone | Metformin + PAP | Placebo Oral Capsule + PAP |
|---|---|---|
| Started | 8 | 8 |
| Completed | 7 | 8 |
| Not completed | 1 | 0 |
| Withdrew: Withdrawal by subject | 1 | 0 |
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.
| Index | Metformin + PAP | Placebo Oral Capsule + PAP |
|---|---|---|
| Changes in Matsuda Index | 0.395 ± 1.695 | -0.649 ± 1.974 |
Comparison of change in insulin AUC (area under the curve) as derived from 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. 2-h insulin AUC is calculated using trapezoid method. Higher AUC indicates higher insulin secretion.
| uU*120min/mL | Metformin + PAP | Placebo Oral Capsule + PAP |
|---|---|---|
| Changes in Insulin Area Under the Curve (AUC) During 2-h Oral Glucose Tolerance Test (OGTT) | -855 ± 3334 | 4222 ± 4482 |
Comparison of change in glucose AUC (area under the curve) as derived from 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. 2-h glucose AUC is calculated using trapezoid method. Higher AUC indicates higher levels of circulating glucose.
| mg*120min/dL | Metformin + PAP | Placebo Oral Capsule + PAP |
|---|---|---|
| Changes in Glucose Area Under the Curve (AUC) During 2-h Oral Glucose Tolerance Test (OGTT) | -1759 ± 4260 | 698 ± 2754 |
Comparison of insulinogenic index derived from the initial 30 min data from the 2-h oral glucose tolerance test (OGTT). Insulinogenic index measures the early insulin response during the oral glucose challenge. The index is calculated as ratio of change in insulin to glucose from 0 to 30 min values derived from OGTT. Decrease in scores reflect improvement in insulin sensitivity.
| Index | Metformin + PAP | Placebo Oral Capsule + PAP |
|---|---|---|
| Changes in Insulinogenic Index | 0.201 ± 0.497 | 0.206 ± 0.529 |
Comparison of change in disposition index as derived from 2-h oral glucose tolerance test. Disposition index measures beta-cell function and is calculated as product of Matsuda index and Insulinogenic index values. Increase in scores reflect improvement in glucose metabolism.
| Index | Metformin + PAP | Placebo Oral Capsule + PAP |
|---|---|---|
| Changes in Disposition Index | 0.617 ± 1.357 | -0.012 ± 1.726 |
Comparison of change in HOMA-IR value derived from fasting insulin and glucose. HOMA-IR is a simple index for insulin resistance based on fasting measures of glucose and insulin which is a commonly used end-point for assessment of insulin resistance in clinical trials. HOMA-IR is calculated as \[(fasting insulin X fasting glucose)/ 22.5\]. Higher values indicate higher insulin resistance. An increase will suggest a detrimental effect on glucose metabolism. Individuals with HOMA-IR \< 5.7% are considered healthy, between 5.7 and 6.4% are considered prediabetic, and more than 6.4% are considered diabetic.
| Index | Metformin + PAP | Placebo Oral Capsule + PAP |
|---|---|---|
| Changes in Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) | 0.651 ± 2.274 | 1.981 ± 3.406 |
Collected over 3 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Metformin | 0/8 (0%) | 0/8 (0%) | 0/8 (0%) |
| Placebo Oral Capsule | 0/8 (0%) | 0/8 (0%) | 0/8 (0%) |
| Age, Continuous(years) | Metformin + PAP | Placebo Oral Capsule + PAP | Total |
|---|---|---|---|
| Mean | 50.25 ± 8.31 | 51.5 ± 5.04 | 50.88 ± 6.67 |
| Sex: Female, Male(Participants) | Metformin + PAP | Placebo Oral Capsule + PAP | Total |
|---|---|---|---|
| Female | 1 | 2 | 3 |
| Male | 7 | 6 | 13 |
| Race (NIH/OMB)(Participants) | Metformin + PAP | Placebo Oral Capsule + PAP | Total |
|---|---|---|---|
| American Indian or Alaska Native | 1 | 0 | 1 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 7 | 8 | 15 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Metformin + PAP | Placebo Oral Capsule + PAP | Total |
|---|---|---|---|
| United States | 8 | 8 | 16 |
| Body mass index(Kg/m^2) | Metformin + PAP | Placebo Oral Capsule + PAP | Total |
|---|---|---|---|
| Mean | 36.63 ± 2.34 | 36.31 ± 3.48 | 36.47 ± 2.87 |
| Apnea Hypopnea Index(event/h of sleep) | Metformin + PAP | Placebo Oral Capsule + PAP | Total |
|---|---|---|---|
| Mean | 54.4 ± 22.5 | 52.1 ± 21 | 53.3 ± 21.1 |
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