Obstructive Sleep Apnea, Type 2 Diabetes
Conditions
Brief summary
The overall goal of the proposed protocol is to rigorously test the hypothesis that CPAP treatment has beneficial effects on glycemic control in patients with both type 2 diabetes (T2DM) and obstructive sleep apnea (OSA). If our hypothesis were to be proven, this would imply that CPAP treatment of OSA in patients with T2DM is an essential component of their glycemic control. The proposed work is thus expected to provide additional preventive and therapeutic approaches in the management of millions of patients with T2DM.
Interventions
DEVICEactive CPAP Therapy
7 days of active CPAP therapy
DEVICEsham CPAP therapy
7 days of sham CPAP therapy
Sponsors
University of Chicago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female subjects with type 2 diabetes on a stable medication regimen (no change in diabetic medications in the previous 3 months) will be eligible.
Exclusion criteria
* Subjects on insulin will be excluded. * Subjects with unstable cardiopulmonary disease, painful neuropathy, significant psychiatric illness, cognitive impairment and pregnancy will be excluded. * Shift workers * Subjects having traveled across \>2 time zones less than one month prior to the study * Diagnosis of a sleep disorder other than OSA by screening polysomnography * Previous treatment with positive airway pressure or supplemental oxygen * Requirement of supplemental oxygen or bi-level positive airway pressure for OSA treatment during titration * Claustrophobia or other conditions of CPAP intolerance, * Presence of active infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to End of 7-day Intervention in Mean Plasma Glucose Derived From 24 Hour Blood Sampling | after 1 week of CPAP therapy in the laboratory | 24 hour blood sampling will be performed at baseline and at the end of the 7-day intervention. Glucose levels will be measured on each sample. Mean glucose level for all baseline samples will be calculated for each participant. Mean glucose levels for all samples collected at the end of the intervention will be calculated. Change in mean glucose level from baseline to end of intervention will be calculated for each participant. |
| Change From Baseline in Mean Glucose From Continuous Interstitial Glucose Monitoring Over 36-40 Hours | change in mean interstitial glucose after 1 week of active or sham CPAP therapy in the laboratory | Continuous Glucose monitoring will provide interstitial glucose levels for 36-40 hours at baseline and after one week of active or sham CPAP therapy. The mean glucose level of all samples collected at baseline will be calculated for each participant. The mean glucose level of all samples collected at the end of the 7-day intervention will be calculated for each participant. For each participant, we will calculate the change in mean glucose level from baseline till end of the intervention. |
| Change in Mean Serum Insulin Derived From 24 Hour Blood Sampling | after 1 week of therapy in the laboratory | Serum insulin levels will be measured on each sample collected during 24-h sampling at baseline and at the end of the 7-day intervention. Mean insulin level over 24 hours will be calculated for each participant at baseline and at the end of the intervention. For each participant, we will calculate the change in mean insulin level from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Plasma Cortisol Level From 24-h Sampling | after 1 week of active CPAP therapy in the laboratory | The mean plasma cortisol level will be calculated for all samples collected at baseline and for all samples collected at the end of the intervention in participants randomized to the active CPAP arm. The goal of the analysis of cortisol, growth hormone and norepinephrine levels was to explore putative mechanisms underlying the effects of active CPAP therapy. Examining putative hormonal mechanisms underlying changes in glucose levels in the sham CPAP arm was not part of our aims. For each participant, the change in mean cortisol level from baseline to end of intervention will be calculated. |
| 24-hr Profile of Plasma Growth Hormone | after 1 week of active CPAP therapy in the laboratory | The mean plasma growth hormone level will be calculated for all samples collected at baseline and for all samples collected at the end of the intervention in participants randomized to the active CPAP arm. The goal of the analysis of cortisol, growth hormone and norepinephrine levels was to explore putative mechanisms underlying the effects of active CPAP therapy. Examining putative hormonal mechanisms underlying changes in glucose levels in the sham CPAP arm was not part of our aims. For each participant, the change in mean cortisol level from baseline to end of intervention will be calculated. |
| Change in 24-h Mean Level of Plasma Norepinephrine | after 1 week of active CPAP therapy in the laboratory | The mean plasma norepinephrine level will be calculated for all samples collected at baseline and for all samples collected at the end of the intervention in participants randomized to the active CPAP arm. The goal of the analysis of cortisol, growth hormone and norepinephrine levels was to explore putative mechanisms underlying the effects of active CPAP therapy. Examining putative hormonal mechanisms underlying changes in glucose levels in the sham CPAP arm was not part of our aims. For each participant, the change in mean norepinephine level from baseline to end of intervention will be calculated. |
Countries
United States
Participant flow
Recruitment details
In a 2:1 ratio (2 active CPAP: 1 sham CPAP), 22 eligible subjects who had completed baseline assessments underwent 1 week of in-laboratory active CPAP or sham CPAP therapy and completed the post-treatment assessments. Two subjects assigned to the CPAP group and one subject assigned to the sham group were excluded for protocol violations.
Participants by arm
| Arm | Count |
|---|---|
| Active CPAP 7 days of treatment in the laboratory with active CPAP.
Continuous Positive Airway Pressure (CPAP) Therapy (active): CPAP is approved for the treatment of Obstructive Sleep Apnea | 13 |
| Sham CPAP 7 days of sham CPAP in the laboratory. | 6 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 2 | 1 |
Baseline characteristics
| Characteristic | Active CPAP | Total | Sham CPAP |
|---|---|---|---|
| Age, Continuous | 56.2 years STANDARD_DEVIATION 11.4 | 55.0 years STANDARD_DEVIATION 9.6 | 52.3 years STANDARD_DEVIATION 3.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 10 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 6 Participants | 2 Participants |
| Region of Enrollment United States | 13 Participants | 19 Participants | 6 Participants |
| Sex: Female, Male Female | 6 Participants | 10 Participants | 4 Participants |
| Sex: Female, Male Male | 7 Participants | 9 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 7 |
| other Total, other adverse events | 0 / 15 | 0 / 7 |
| serious Total, serious adverse events | 0 / 15 | 0 / 7 |
Outcome results
Primary
Change From Baseline in Mean Glucose From Continuous Interstitial Glucose Monitoring Over 36-40 Hours
Continuous Glucose monitoring will provide interstitial glucose levels for 36-40 hours at baseline and after one week of active or sham CPAP therapy. The mean glucose level of all samples collected at baseline will be calculated for each participant. The mean glucose level of all samples collected at the end of the 7-day intervention will be calculated for each participant. For each participant, we will calculate the change in mean glucose level from baseline till end of the intervention.
Time frame: change in mean interstitial glucose after 1 week of active or sham CPAP therapy in the laboratory
Population: Due to sensor failures, valid profiles of interstitial glucose were available in 10 participants with the active CPAP group and 4 participants in the sham CPAP group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active CPAP | Change From Baseline in Mean Glucose From Continuous Interstitial Glucose Monitoring Over 36-40 Hours | -12.4 mg/dL | Standard Error 3.9 |
| Sham CPAP | Change From Baseline in Mean Glucose From Continuous Interstitial Glucose Monitoring Over 36-40 Hours | 1.5 mg/dL | Standard Error 2.2 |
Comparison: comparing pre and post Interstitial Glucose levels in the active CPAP groupp-value: 0.0112-sided Paired t-test
Primary
Change From Baseline to End of 7-day Intervention in Mean Plasma Glucose Derived From 24 Hour Blood Sampling
24 hour blood sampling will be performed at baseline and at the end of the 7-day intervention. Glucose levels will be measured on each sample. Mean glucose level for all baseline samples will be calculated for each participant. Mean glucose levels for all samples collected at the end of the intervention will be calculated. Change in mean glucose level from baseline to end of intervention will be calculated for each participant.
Time frame: after 1 week of CPAP therapy in the laboratory
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active CPAP | Change From Baseline to End of 7-day Intervention in Mean Plasma Glucose Derived From 24 Hour Blood Sampling | -13.7 mg/dl | Standard Error 3.6 |
| Sham CPAP | Change From Baseline to End of 7-day Intervention in Mean Plasma Glucose Derived From 24 Hour Blood Sampling | -2.9 mg/dl | Standard Error 1.4 |
Comparison: two-sided t test for the change from baseline between the treated and untreated groups.p-value: 0.01t-test, 2 sided
Primary
Change in Mean Serum Insulin Derived From 24 Hour Blood Sampling
Serum insulin levels will be measured on each sample collected during 24-h sampling at baseline and at the end of the 7-day intervention. Mean insulin level over 24 hours will be calculated for each participant at baseline and at the end of the intervention. For each participant, we will calculate the change in mean insulin level from baseline.
Time frame: after 1 week of therapy in the laboratory
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active CPAP | Change in Mean Serum Insulin Derived From 24 Hour Blood Sampling | -25.8 pmol/L | Standard Error 16.5 |
| Sham CPAP | Change in Mean Serum Insulin Derived From 24 Hour Blood Sampling | 28.4 pmol/L | Standard Error 21.6 |
p-value: 0.071t-test, 2 sided
Secondary
24-hr Profile of Plasma Growth Hormone
The mean plasma growth hormone level will be calculated for all samples collected at baseline and for all samples collected at the end of the intervention in participants randomized to the active CPAP arm. The goal of the analysis of cortisol, growth hormone and norepinephrine levels was to explore putative mechanisms underlying the effects of active CPAP therapy. Examining putative hormonal mechanisms underlying changes in glucose levels in the sham CPAP arm was not part of our aims. For each participant, the change in mean cortisol level from baseline to end of intervention will be calculated.
Time frame: after 1 week of active CPAP therapy in the laboratory
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Active CPAP | 24-hr Profile of Plasma Growth Hormone | -0.02 ng/ml |
Comparison: comparing pre and post levels in the active CPAP groupp-value: 0.308two-sided paired t-test
Secondary
Change in 24-h Mean Level of Plasma Norepinephrine
The mean plasma norepinephrine level will be calculated for all samples collected at baseline and for all samples collected at the end of the intervention in participants randomized to the active CPAP arm. The goal of the analysis of cortisol, growth hormone and norepinephrine levels was to explore putative mechanisms underlying the effects of active CPAP therapy. Examining putative hormonal mechanisms underlying changes in glucose levels in the sham CPAP arm was not part of our aims. For each participant, the change in mean norepinephine level from baseline to end of intervention will be calculated.
Time frame: after 1 week of active CPAP therapy in the laboratory
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Active CPAP | Change in 24-h Mean Level of Plasma Norepinephrine | -60.9 pg/ml |
Comparison: comparing pre and post levels in the active CPAP groupp-value: 0.036two-sided paired t-test
Secondary
Change in Mean Plasma Cortisol Level From 24-h Sampling
The mean plasma cortisol level will be calculated for all samples collected at baseline and for all samples collected at the end of the intervention in participants randomized to the active CPAP arm. The goal of the analysis of cortisol, growth hormone and norepinephrine levels was to explore putative mechanisms underlying the effects of active CPAP therapy. Examining putative hormonal mechanisms underlying changes in glucose levels in the sham CPAP arm was not part of our aims. For each participant, the change in mean cortisol level from baseline to end of intervention will be calculated.
Time frame: after 1 week of active CPAP therapy in the laboratory
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Active CPAP | Change in Mean Plasma Cortisol Level From 24-h Sampling | -0.1 microgram/dL |
Comparison: Plasma cortisol pre and post 1-week of active CPAPp-value: 0.754two-sided paired t-test