Trial Outcomes & Findings for Metabolic Effects of Metformin Therapy in Obstructive Sleep Apnea (NCT NCT04530747)
NCT ID: NCT04530747
Last Updated: 2023-01-19
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
16 participants
Primary outcome timeframe
approximately 4 months, includes measures obtained at baseline and 3 month follow-up.
Results posted on
2023-01-19
Participant Flow
Participant milestones
| Measure |
Metformin + PAP
Subjects randomized to this arm will be orally given 2000 mg metformin daily. Metformin dosage will be slowly increased to improve tolerance.
Metformin: 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 positive airway pressure (PAP) device for standard management of obstructive sleep apnea.
|
Placebo Oral Capsule + PAP
Subjects randomized to this arm will receive placebo matching study drug.
Placebo oral capsule: Subjects randomized to this arm will receive 500 mg capsules containing placebo. Placebo 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 positive airway pressure (PAP) device for standard management of obstructive sleep apnea.
|
|---|---|---|
|
Overall Study
STARTED
|
8
|
8
|
|
Overall Study
COMPLETED
|
7
|
8
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Metformin + PAP
Subjects randomized to this arm will be orally given 2000 mg metformin daily. Metformin dosage will be slowly increased to improve tolerance.
Metformin: 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 positive airway pressure (PAP) device for standard management of obstructive sleep apnea.
|
Placebo Oral Capsule + PAP
Subjects randomized to this arm will receive placebo matching study drug.
Placebo oral capsule: Subjects randomized to this arm will receive 500 mg capsules containing placebo. Placebo 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 positive airway pressure (PAP) device for standard management of obstructive sleep apnea.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Metabolic Effects of Metformin Therapy in Obstructive Sleep Apnea
Baseline characteristics by cohort
| Measure |
Metformin + PAP
n=8 Participants
Subjects randomized to this arm will be orally given 2000 mg metformin daily. Metformin dosage will be slowly increased to improve tolerance.
Metformin: Subjects randomized to this arm will receive 500 mg capsules containing metformin XR. Metformin XR 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
n=8 Participants
Subjects randomized to this arm will receive placebo matching study drug.
Placebo oral capsule: 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.
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
50.25 years
STANDARD_DEVIATION 8.31 • n=5 Participants
|
51.5 years
STANDARD_DEVIATION 5.04 • n=7 Participants
|
50.88 years
STANDARD_DEVIATION 6.67 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
8 participants
n=5 Participants
|
8 participants
n=7 Participants
|
16 participants
n=5 Participants
|
|
Body mass index
|
36.63 Kg/m^2
STANDARD_DEVIATION 2.34 • n=5 Participants
|
36.31 Kg/m^2
STANDARD_DEVIATION 3.48 • n=7 Participants
|
36.47 Kg/m^2
STANDARD_DEVIATION 2.87 • n=5 Participants
|
|
Apnea Hypopnea Index
|
54.4 event/h of sleep
STANDARD_DEVIATION 22.5 • n=5 Participants
|
52.1 event/h of sleep
STANDARD_DEVIATION 21 • n=7 Participants
|
53.3 event/h of sleep
STANDARD_DEVIATION 21.1 • n=5 Participants
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Metformin + PAP
n=7 Participants
Subjects randomized to this arm will be orally given 2000 mg metformin daily. Metformin dosage will be slowly increased to improve tolerance.
Metformin: Subjects randomized to this arm will receive 500 mg capsules containing metformin XR. Metformin XR 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
n=8 Participants
Subjects randomized to this arm will receive placebo matching study drug.
Placebo oral capsule: 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
|
0.395 Index
Standard Deviation 1.695
|
-0.649 Index
Standard Deviation 1.974
|
SECONDARY outcome
Timeframe: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.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.
Outcome measures
| Measure |
Metformin + PAP
n=7 Participants
Subjects randomized to this arm will be orally given 2000 mg metformin daily. Metformin dosage will be slowly increased to improve tolerance.
Metformin: Subjects randomized to this arm will receive 500 mg capsules containing metformin XR. Metformin XR 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
n=8 Participants
Subjects randomized to this arm will receive placebo matching study drug.
Placebo oral capsule: 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 Insulin Area Under the Curve (AUC) During 2-h Oral Glucose Tolerance Test (OGTT)
|
-855 uU*120min/mL
Standard Deviation 3334
|
4222 uU*120min/mL
Standard Deviation 4482
|
SECONDARY outcome
Timeframe: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.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.
Outcome measures
| Measure |
Metformin + PAP
n=7 Participants
Subjects randomized to this arm will be orally given 2000 mg metformin daily. Metformin dosage will be slowly increased to improve tolerance.
Metformin: Subjects randomized to this arm will receive 500 mg capsules containing metformin XR. Metformin XR 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
n=8 Participants
Subjects randomized to this arm will receive placebo matching study drug.
Placebo oral capsule: 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 Glucose Area Under the Curve (AUC) During 2-h Oral Glucose Tolerance Test (OGTT)
|
-1759 mg*120min/dL
Standard Deviation 4260
|
698 mg*120min/dL
Standard Deviation 2754
|
SECONDARY outcome
Timeframe: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.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.
Outcome measures
| Measure |
Metformin + PAP
n=7 Participants
Subjects randomized to this arm will be orally given 2000 mg metformin daily. Metformin dosage will be slowly increased to improve tolerance.
Metformin: Subjects randomized to this arm will receive 500 mg capsules containing metformin XR. Metformin XR 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
n=8 Participants
Subjects randomized to this arm will receive placebo matching study drug.
Placebo oral capsule: 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 Insulinogenic Index
|
0.201 Index
Standard Deviation 0.497
|
0.206 Index
Standard Deviation 0.529
|
SECONDARY outcome
Timeframe: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.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.
Outcome measures
| Measure |
Metformin + PAP
n=7 Participants
Subjects randomized to this arm will be orally given 2000 mg metformin daily. Metformin dosage will be slowly increased to improve tolerance.
Metformin: Subjects randomized to this arm will receive 500 mg capsules containing metformin XR. Metformin XR 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
n=8 Participants
Subjects randomized to this arm will receive placebo matching study drug.
Placebo oral capsule: 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 Disposition Index
|
0.617 Index
Standard Deviation 1.357
|
-0.012 Index
Standard Deviation 1.726
|
SECONDARY outcome
Timeframe: approximately 4 months, includes measures obtained at baseline and 3 month follow-up.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.
Outcome measures
| Measure |
Metformin + PAP
n=7 Participants
Subjects randomized to this arm will be orally given 2000 mg metformin daily. Metformin dosage will be slowly increased to improve tolerance.
Metformin: Subjects randomized to this arm will receive 500 mg capsules containing metformin XR. Metformin XR 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
n=8 Participants
Subjects randomized to this arm will receive placebo matching study drug.
Placebo oral capsule: 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 Homeostasis Model Assessment for Insulin Resistance (HOMA-IR)
|
0.651 Index
Standard Deviation 2.274
|
1.981 Index
Standard Deviation 3.406
|
Adverse Events
Metformin
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo Oral Capsule
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place