Impact of Exenatide on Sleep in Type 2 Diabetes

• Sponsor: University of Chicago (Other)
• Overall Status: Completed
• CT.gov ID: NCT01136798
• Collaborator: (none)
• Enrollment: 18
• Locations: 2
• Arms: 2
• Actual Duration (Months): 75
• Patients Per Site: 9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes; Sleep Disordered Breathing	Drug: Exenatide; Drug: Placebo	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Impact of Exenatide on Sleep and Circadian Function in Type 2 Diabetes: A Pilot Study
• Actual Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Sep 1, 2016
• Actual Study Completion Date: Sep 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 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.	Drug: Placebo; Exenatide or placebo medication administered subcutaneously 5 mcg twice daily for 2 weeks, followed by 10 mcg twice daily for 4 weeks
Experimental: 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.	Drug: Exenatide; Exenatide or placebo medication administered subcutaneously 5 mcg twice daily for 2 weeks, followed by 10 mcg twice daily for 4 weeks

Outcome Measures

Primary Outcome Measures

1. Non-REM Slow Wave Sleep [baseline and after 6 weeks of treatment]

   Total minutes of non-REM sleep was measured

2. 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 Outcome Measures

1. 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.

2. 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

3. 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.

4. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Chicago	Chicago	Illinois	United States	60637
2	University of Chicago	Chicago	Illinois	United States	60637

Sponsors and Collaborators

• University of Chicago

Investigators

• Principal Investigator: Eve Van Cauter, PhD, University of Chicago

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Chicago
• ClinicalTrials.gov Identifier: NCT01136798
• Other Study ID Numbers: 09-291-B
• First Posted: Jun 3, 2010
• Last Update Posted: Sep 12, 2018
• Last Verified: Aug 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by University of Chicago: slow wave sleep; exenatide and sleep
• Additional relevant MeSH terms: Sleep Apnea Syndromes; Diabetes Mellitus; Diabetes Mellitus, Type 2; Exenatide

Study Results

Participant Flow

Arm/Group Title	Usual T2 DM Med Regimen	Usual T2 DM Med Regimen Plus Exenatide
Arm/Group Description	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	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
Period Title: Overall Study
STARTED	10	8
COMPLETED	10	8
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Usual T2 DM Med Regimen	Usual T2 DM Med Regimen Plus Exenatide	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	10	8	18
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59 (7.6)	52.8 (8.6)	56.2 (8.6)
Sex: Female, Male (Count of Participants)
Female	8 80%	6 75%	14 77.8%
Male	2 20%	2 25%	4 22.2%
Race/Ethnicity, Customized (Count of Participants)
African-American	5 50%	7 87.5%	12 66.7%
Non-Hispanic White	4 40%	0 0%	4 22.2%
Hispanic	1 10%	1 12.5%	2 11.1%

Outcome Measures

1. Primary Outcome

Title	Non-REM Slow Wave Sleep
Description	Total minutes of non-REM sleep was measured
Time Frame	baseline and after 6 weeks of treatment

Outcome Measure Data

Analysis Population Description

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/Group Title	Usual T2 DM Med Regimen	Usual T2 DM Med Regimen Plus Exenatide
Arm/Group Description	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	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
Measure Participants	9	7
Baseline	47.3 (37.3)	34.3 (34.4)
At 6 week	57.3 (38.1)	41.4 (40.3)

2. Primary Outcome

Title	Total Amount of Slow Wave Activity
Description	Total amount of slow wave activity during sleep derived from laboratory polysomnogram was measured
Time Frame	baseline and after 6 weeks of treatment

Outcome Measure Data

Analysis Population Description

The second primary outcome measure, slow-wave activity (SWA) was not collected.

Arm/Group Title	Usual T2 DM Med Regimen	Usual T2 DM Med Regimen Plus Exenatide
Arm/Group Description	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	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
Measure Participants	0	0

3. Secondary Outcome

Title	Sleep Efficiency During Polysomnographic Recording
Description	Sleep efficiency will be calculated as total sleep time over total recording time.
Time Frame	baseline and after 6 weeks of treatment

Outcome Measure Data

Analysis Population Description

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/Group Title	Usual T2 DM Med Regimen	Usual T2 DM Med Regimen Plus Exenatide
Arm/Group Description	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	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
Measure Participants	9	7
Baseline	84.3 (6.8)	85.3 (6.1)
At 6 week	83.8 (9.2)	89.4 (5.4)

4. Secondary Outcome

Title	Minutes of Wake After Sleep Onset During Sleep Recording
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Usual T2 DM Med Regimen	Usual T2 DM Med Regimen Plus Exenatide
Arm/Group Description	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	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
Measure Participants	9	7
Baseline	70.4 (33.1)	56.6 (23)
At 6 week	52.3 (26.7)	36.6 (18.7)

5. Secondary Outcome

Title	Severity of Obstructive Sleep Apnea
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Usual T2 DM Med Regimen	Usual T2 DM Med Regimen Plus Exenatide
Arm/Group Description	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	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
Measure Participants	9	7
Baseline	15.9 (9.6)	16.4 (10.9)
At 6 week	16.5 (11.4)	10.9 (10.2)

6. Secondary Outcome

Title	Mean 24-h Blood Glucose Levels
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Usual T2 DM Med Regimen	Usual T2 DM Med Regimen Plus Exenatide
Arm/Group Description	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	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
Measure Participants	10	8
Baseline	134.4 (18.1)	142.2 (37.5)
At 6 week	141.3 (22.1)	136.1 (39.2)

Adverse Events

Time Frame	6 weeks
Arm/Group Title	Usual T2 DM Med Regimen		Usual T2 DM Med Regimen Plus Exenatide
Arm/Group Description	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		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
All Cause Mortality
	Usual T2 DM Med Regimen		Usual T2 DM Med Regimen Plus Exenatide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Usual T2 DM Med Regimen		Usual T2 DM Med Regimen Plus Exenatide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Usual T2 DM Med Regimen		Usual T2 DM Med Regimen Plus Exenatide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/8 (0%)

Limitations/Caveats

When the investigators were unblinded in August 2016, a randomization error originating from the industry sponsor was identified, where only 8 participants were randomized to exenatide while 10 were randomized to placebo.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.