Sleep Disordered Breathing, Type 2 Diabetes
Conditions
Keywords
slow wave sleep, exenatide and sleep
Brief summary
The investigators propose a pilot study to test the novel hypothesis that Exenatide treatment in patients with type 2 diabetes results in improved sleep duration and quality and to explore the relationship between improvements in sleep and measures of metabolic and circadian function. This project would be the first to probe the relationship between incretin hormone regulation, duration and intensity of sleep, glucose tolerance and circadian dysfunction in diabetic patients.
Interventions
DRUGExenatide
Exenatide or placebo medication administered subcutaneously 5 mcg twice daily for 2 weeks, followed by 10 mcg twice daily for 4 weeks
DRUGPlacebo
Exenatide or placebo medication administered subcutaneously 5 mcg twice daily for 2 weeks, followed by 10 mcg twice daily for 4 weeks
Sponsors
University of Chicago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with a diagnosis of T2DM based on physician documentation according to established guidelines will be eligible.
Exclusion criteria
* Patients with unstable cardiac, neurological or psychiatric disease * Women who are pregnant or report trying to get pregnant will be excluded. * Patients treated for obstructive sleep apnea (OSA) will be excluded. * Patients with established OSA will be included only if they have declined treatment of OSA. * Patients with morbid obesity (BMI ≥ 40 gk/m2) * Patients on insulin * Patients already taking an incretin-based drug will not be included * Patients with renal disease (creatinine clearance \<30 ml/min), gastroparesis and history of pancreatitis will also be excluded based on known possible adverse medication side effects. * Patients taking an insulin secretagogue will be excluded. * Patients with Hemoglobin A1c values greater than or equal to 10 will be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Non-REM Slow Wave Sleep | baseline and after 6 weeks of treatment | Total minutes of non-REM sleep was measured |
| Total Amount of Slow Wave Activity | baseline and after 6 weeks of treatment | Total amount of slow wave activity during sleep derived from laboratory polysomnogram was measured |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sleep Efficiency During Polysomnographic Recording | baseline and after 6 weeks of treatment | Sleep efficiency will be calculated as total sleep time over total recording time. |
| Minutes of Wake After Sleep Onset During Sleep Recording | baseline and after 6 weeks of treatment | total amount of time spent awake after sleep onset and before morning awakening will be calculated |
| Severity of Obstructive Sleep Apnea | baseline and after 6 weeks of treatment | The apnea-hypopnea index (AHI) will be calculated from polysomnographic recordings. The minimum score for AHI is 0 (zero), corresponding to total absence of apnea or hypopnea. There is no theoretical maximum score although scores above 100 are very rarely observed. The lower the AHI value, the better. Higher AHI values correspond to greater severity of sleep apnea, a worse outcome. There are no subscales. We use continuous AHI values to measure severity of obstructive sleep apnea. |
| Mean 24-h Blood Glucose Levels | baseline and after 6 weeks of treatment | Mean plasma levels of glucose will be calculated from samples collected across the 24-h cycle. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Usual T2 DM Med Regimen Subjects will continue on Type 2 DM therapy but will add placebo injected subcutaneously twice daily to their regimen for a total of 6 weeks.
Placebo: Exenatide or placebo medication administered subcutaneously 5 mcg twice daily for 2 weeks, followed by 10 mcg twice daily for 4 weeks | 10 |
| Usual T2 DM Med Regimen Plus Exenatide Subjects will continue on Type 2 DM therapy but will add injectable exenatide to their regimen There will be twice daily treatment with subcutaneous injections of 5 µg of Exenatide for 2 weeks followed by 4 weeks of treatment with twice daily subcutaneous injections of 10 µg of Exenatide.
Exenatide: Exenatide or placebo medication administered subcutaneously 5 mcg twice daily for 2 weeks, followed by 10 mcg twice daily for 4 weeks | 8 |
| Total | 18 |
Baseline characteristics
| Characteristic | Usual T2 DM Med Regimen | Usual T2 DM Med Regimen Plus Exenatide | Total |
|---|---|---|---|
| Age, Continuous | 59 years STANDARD_DEVIATION 7.6 | 52.8 years STANDARD_DEVIATION 8.6 | 56.2 years STANDARD_DEVIATION 8.6 |
| Race/Ethnicity, Customized African-American | 5 Participants | 7 Participants | 12 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Non-Hispanic White | 4 Participants | 0 Participants | 4 Participants |
| Sex: Female, Male Female | 8 Participants | 6 Participants | 14 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 10 | 0 / 8 |
| serious Total, serious adverse events | 0 / 10 | 0 / 8 |
Outcome results
Primary
Non-REM Slow Wave Sleep
Total minutes of non-REM sleep was measured
Time frame: baseline and after 6 weeks of treatment
Population: The Electronic Sleep Recordings for one participant in Usual T2 DM med regimen were corrupted and could not be analyzed. One participant in Usual T2 DM med regimen plus Exenatide had a very short sleep periods during the study and his data could not be interpreted, therefore this patient was excluded from the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Usual T2 DM Med Regimen | Non-REM Slow Wave Sleep | Baseline | 47.3 minutes | Standard Deviation 37.3 |
| Usual T2 DM Med Regimen | Non-REM Slow Wave Sleep | At 6 week | 57.3 minutes | Standard Deviation 38.1 |
| Usual T2 DM Med Regimen Plus Exenatide | Non-REM Slow Wave Sleep | Baseline | 34.3 minutes | Standard Deviation 34.4 |
| Usual T2 DM Med Regimen Plus Exenatide | Non-REM Slow Wave Sleep | At 6 week | 41.4 minutes | Standard Deviation 40.3 |
Primary
Total Amount of Slow Wave Activity
Total amount of slow wave activity during sleep derived from laboratory polysomnogram was measured
Time frame: baseline and after 6 weeks of treatment
Population: The second primary outcome measure, slow-wave activity (SWA) was not collected.
Secondary
Mean 24-h Blood Glucose Levels
Mean plasma levels of glucose will be calculated from samples collected across the 24-h cycle.
Time frame: baseline and after 6 weeks of treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Usual T2 DM Med Regimen | Mean 24-h Blood Glucose Levels | Baseline | 134.4 mg/dl | Standard Deviation 18.1 |
| Usual T2 DM Med Regimen | Mean 24-h Blood Glucose Levels | At 6 week | 141.3 mg/dl | Standard Deviation 22.1 |
| Usual T2 DM Med Regimen Plus Exenatide | Mean 24-h Blood Glucose Levels | Baseline | 142.2 mg/dl | Standard Deviation 37.5 |
| Usual T2 DM Med Regimen Plus Exenatide | Mean 24-h Blood Glucose Levels | At 6 week | 136.1 mg/dl | Standard Deviation 39.2 |
Secondary
Minutes of Wake After Sleep Onset During Sleep Recording
total amount of time spent awake after sleep onset and before morning awakening will be calculated
Time frame: baseline and after 6 weeks of treatment
Population: The Electronic Sleep Recordings for one participant in Usual T2 DM med regimen were corrupted and could not be analyzed. One participant in Usual T2 DM med regimen plus Exenatide had a very short sleep periods during the study and his data could not be interpreted, therefore this patient was excluded from the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Usual T2 DM Med Regimen | Minutes of Wake After Sleep Onset During Sleep Recording | Baseline | 70.4 minutes | Standard Deviation 33.1 |
| Usual T2 DM Med Regimen | Minutes of Wake After Sleep Onset During Sleep Recording | At 6 week | 52.3 minutes | Standard Deviation 26.7 |
| Usual T2 DM Med Regimen Plus Exenatide | Minutes of Wake After Sleep Onset During Sleep Recording | Baseline | 56.6 minutes | Standard Deviation 23 |
| Usual T2 DM Med Regimen Plus Exenatide | Minutes of Wake After Sleep Onset During Sleep Recording | At 6 week | 36.6 minutes | Standard Deviation 18.7 |
Secondary
Severity of Obstructive Sleep Apnea
The apnea-hypopnea index (AHI) will be calculated from polysomnographic recordings. The minimum score for AHI is 0 (zero), corresponding to total absence of apnea or hypopnea. There is no theoretical maximum score although scores above 100 are very rarely observed. The lower the AHI value, the better. Higher AHI values correspond to greater severity of sleep apnea, a worse outcome. There are no subscales. We use continuous AHI values to measure severity of obstructive sleep apnea.
Time frame: baseline and after 6 weeks of treatment
Population: The Electronic Sleep Recordings for one participant in Usual T2 DM med regimen were corrupted and could not be analyzed. One participant in Usual T2 DM med regimen plus Exenatide had a very short sleep periods during the study and his data could not be interpreted, therefore this patient was excluded from the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Usual T2 DM Med Regimen | Severity of Obstructive Sleep Apnea | Baseline | 15.9 units on a scale | Standard Deviation 9.6 |
| Usual T2 DM Med Regimen | Severity of Obstructive Sleep Apnea | At 6 week | 16.5 units on a scale | Standard Deviation 11.4 |
| Usual T2 DM Med Regimen Plus Exenatide | Severity of Obstructive Sleep Apnea | Baseline | 16.4 units on a scale | Standard Deviation 10.9 |
| Usual T2 DM Med Regimen Plus Exenatide | Severity of Obstructive Sleep Apnea | At 6 week | 10.9 units on a scale | Standard Deviation 10.2 |
Secondary
Sleep Efficiency During Polysomnographic Recording
Sleep efficiency will be calculated as total sleep time over total recording time.
Time frame: baseline and after 6 weeks of treatment
Population: The Electronic Sleep Recordings for one participant in Usual T2 DM med regimen were corrupted and could not be analyzed. One participant in Usual T2 DM med regimen plus Exenatide had a very short sleep periods during the study and his data could not be interpreted, therefore this patient was excluded from the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Usual T2 DM Med Regimen | Sleep Efficiency During Polysomnographic Recording | At 6 week | 83.8 percentage of total recording time | Standard Deviation 9.2 |
| Usual T2 DM Med Regimen | Sleep Efficiency During Polysomnographic Recording | Baseline | 84.3 percentage of total recording time | Standard Deviation 6.8 |
| Usual T2 DM Med Regimen Plus Exenatide | Sleep Efficiency During Polysomnographic Recording | Baseline | 85.3 percentage of total recording time | Standard Deviation 6.1 |
| Usual T2 DM Med Regimen Plus Exenatide | Sleep Efficiency During Polysomnographic Recording | At 6 week | 89.4 percentage of total recording time | Standard Deviation 5.4 |