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Sleep Loss and Mechanisms of Impaired Glucose Metabolism

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ClinicalTrials.gov Identifier: NCT00555750
Recruitment Status : Completed
First Posted : November 9, 2007
Results First Posted : September 25, 2013
Last Update Posted : December 10, 2013
Sponsor:
Collaborators:
Sunovion
Mclean Hospital
National Center for Research Resources (NCRR)
Information provided by (Responsible Party):
John W. Winkelman, MD, PhD, Brigham and Women's Hospital

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Basic Science
Condition Primary Insomnia
Interventions Drug: eszopiclone
Drug: placebo
Enrollment 20
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Eszopiclone Placebo
Hide Arm/Group Description nightly active medication (eszopiclone, 3 mg tablet) oral administration ~30 min before bed nightly placebo (identical tablet to active medication) oral administration ~30 min before bed
Period Title: Overall Study
Started 10 10
Completed 10 10
Not Completed 0 0
Arm/Group Title Active Placebo Total
Hide Arm/Group Description active medication administration nightly before bed nightly administration of placebo before bed Total of all reporting groups
Overall Number of Baseline Participants 10 10 20
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 20 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
10
 100.0%
10
 100.0%
20
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 10 participants 20 participants
Female
2
  20.0%
7
  70.0%
9
  45.0%
Male
8
  80.0%
3
  30.0%
11
  55.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 10 participants 10 participants 20 participants
10 10 20
1.Primary Outcome
Title Change in Glucose Tolerance (Kg) in Response to Insulin-modified Intravenous Glucose Tolerance Test
Hide Description Difference in glucose tolerance (Kg) in response to insulin-modified intravenous glucose tolerance test. Glucose tolerance was calculated as the slope of the natural log of declining glucose values from minute 5 to minute 19 post-infusion. By convention, this negative slope is multiplied by -1, in other words, expressed as a rate of disposal.
Time Frame baseline and 2 months post-treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Active Placebo
Hide Arm/Group Description:
active medication administration nightly before bed
nightly administration of placebo before bed
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: %/min, slope of natural log glucose
.33  (.94) -0.10  (.42)
2.Secondary Outcome
Title Acute Insulin Response to Glucose (AIRg)
Hide Description Change over two months in 1st phase Insulin secretion
Time Frame baseline and 2 months post-treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Active Placebo
Hide Arm/Group Description:
active medication administration nightly before bed
nightly administration of placebo before bed
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: mU*l^-1*min
94.0  (269.0) 25.1  (74.7)
3.Secondary Outcome
Title Change in Insulin Sensitivity (SI)
Hide Description

Insulin sensitivity index (SI) "was defined in quantitative terms as the effect of insulin to catalyse the disappearance of glucose from plasma." [R. Bergman, Horm Res 2005;64(suppl 3):8-15].

SI calculated using Bergman's Minimal model analyses (Minmod Millennium 2000; R. Bergman, University of South- ern California, Los Angeles, CA)

Time Frame baseline and 2 months post-treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Active Placebo
Hide Arm/Group Description:
active medication administration nightly before bed
nightly administration of placebo before bed
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: mU/l)^-1*min^-1
-1.19  (2.57) 0.05  (3.43)
4.Secondary Outcome
Title Change in Glucose Effectiveness (SG)
Hide Description

Glucose effectiveness was defined as "the ability of glucose itself to enhance its own disappearance independent of an increment in insulin." [R. Bergman, Horm Res 2005;64(suppl 3):8-15].

SG calculated using Bergman's Minimal model analyses (Minmod Millennium 2000; R. Bergman, University of South- ern California, Los Angeles, CA)

Time Frame baseline and 2 months post-treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Active Placebo
Hide Arm/Group Description:
active medication administration nightly before bed
nightly administration of placebo before bed
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: min^-1
0.001  (0.004) 0.001  (0.009)
5.Secondary Outcome
Title Change in HbA1c Levels
Hide Description Difference in HbA1c levels following two months treatment with eszopiclone versus placebo
Time Frame baseline and 2 months post-treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Active Placebo
Hide Arm/Group Description:
active medication administration nightly before bed
nightly administration of placebo before bed
Overall Number of Participants Analyzed 10 10
Mean (Standard Error)
Unit of Measure: percentage of glycosylation
.03  (.11) -.09  (.06)
6.Secondary Outcome
Title Pre-Treatment Leptin Levels
Hide Description Leptin Levels prior to two months treatment with eszopiclone or placebo, measure after an overnight fast
Time Frame baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Active Placebo
Hide Arm/Group Description:
active medication administration nightly before bed
nightly administration of placebo before bed
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: ng/mL
4.99  (3.63) 16.53  (11.37)
7.Secondary Outcome
Title Post-treatment Leptin Levels
Hide Description Leptin levels following two months treatment with 3mg eszopiclone or placebo, measured after an overnight fast
Time Frame two months post-treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Active Placebo
Hide Arm/Group Description:
active medication administration nightly before bed
nightly administration of placebo before bed
Overall Number of Participants Analyzed 9 10
Mean (Standard Deviation)
Unit of Measure: ng/mL
5.49  (4.33) 15.28  (9.94)
8.Secondary Outcome
Title Pre-treatment Ghrelin Levels
Hide Description Ghrelin levels prior to two months treatment with 3mg eszopiclone or placebo, measured after an overnight fast
Time Frame baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Active Placebo
Hide Arm/Group Description:
active medication administration nightly before bed
nightly administration of placebo before bed
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: ng/mL
573.14  (336.50) 648.41  (230.95)
9.Secondary Outcome
Title Post-treatment Ghrelin Levels
Hide Description Ghrelin levels following two months treatment with 3mg eszopiclone or placebo, measured after an overnight fast
Time Frame 2 months post-treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Active Placebo
Hide Arm/Group Description:
active medication administration nightly before bed
nightly administration of placebo before bed
Overall Number of Participants Analyzed 9 10
Mean (Standard Deviation)
Unit of Measure: ng/mL
544.95  (273.65) 670.94  (180.36)
10.Secondary Outcome
Title Change in Subjective Sleepiness as Measured on the Karolinska Sleepiness Scale (KSS)
Hide Description At visits before and after two months treatment with 3mg eszopiclone or placebo, subjects completed a short test battery including the Karolinska Sleepiness Scale (KSS) every three hours during wake periods. KSS is a single-item scale of sleepiness on a scale from 1 ("very alert") to 9 ("very sleepy, fighting sleep, an effort to keep awake"). Subjective sleepiness was defined as mean deviation from baseline KSS.
Time Frame baseline and 2 months post-treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Active Placebo
Hide Arm/Group Description:
active medication administration nightly before bed
nightly administration of placebo before bed
Overall Number of Participants Analyzed 10 10
Mean (Standard Error)
Unit of Measure: units on a scale
0.53  (0.42) 0.38  (0.38)
11.Secondary Outcome
Title Change in Mean Lapses of Attention
Hide Description At visits before and after two months treatment with 3mg eszopiclone or placebo, subjects completed a short test battery every three hours during wake periods. The battery included the Psychomotor Vigilance Task (PVT). The PVT involved a 10-minute visual reaction time (RT) performance test in which the subject was instructed to maintain the fastest possible RT to a simple visual stimulus. Lapses of attention refer to the number of times the subject failed to respond to the signal within 500ms. Mean lapses per test across 6 tests given a 4 hour intervals during normal waking hours (and not during the IVGTT) during the 30-hr were compared for the post-treatment visit as the absolute deviation from the baseline mean lapses/test.
Time Frame baseline and 2 months post-treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Active Placebo
Hide Arm/Group Description:
active medication administration nightly before bed
nightly administration of placebo before bed
Overall Number of Participants Analyzed 10 10
Mean (Standard Error)
Unit of Measure: lapses of attention
-0.04  (0.49) 0.07  (0.29)
12.Secondary Outcome
Title Change in Total Sleep Time as Reported in Sleep Diaries
Hide Description Total sleep time reported on sleep diaries prior to treatment with 3mg eszopiclone or placebo. Change defined as baseline minus post-treatment).
Time Frame baseline and 2 months post-treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Active Placebo
Hide Arm/Group Description:
active medication administration nightly before bed
nightly administration of placebo before bed
Overall Number of Participants Analyzed 9 10
Mean (Standard Deviation)
Unit of Measure: hours
.58  (.36) .09  (.01)
13.Secondary Outcome
Title Change in Total Sleep Time Measured by PSG
Hide Description Change (baseline minus post-treatment) in total sleep time measured by polysomnography after two months treatment with 3mg eszopiclone or placebo
Time Frame baseline and 2 months post-treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Active Placebo
Hide Arm/Group Description:
active medication administration nightly before bed
nightly administration of placebo before bed
Overall Number of Participants Analyzed 10 10
Mean (Standard Deviation)
Unit of Measure: minutes
2.9  (25.5) -6.4  (30.2)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Active Placebo
Hide Arm/Group Description active medication administration nightly before bed nightly administration of placebo before bed
All-Cause Mortality
Active Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Active Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/10 (0.00%)      0/10 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Active Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/10 (100.00%)      10/10 (100.00%)    
Cardiac disorders     
Dizziness  1  3/10 (30.00%)  3 2/10 (20.00%)  3
Eye disorders     
Eye irritation  1  1/10 (10.00%)  1 0/10 (0.00%)  0
Gastrointestinal disorders     
Abdominal Discomfort   1/10 (10.00%)  3 2/10 (20.00%)  2
Constipation  1  1/10 (10.00%)  1 0/10 (0.00%)  0
Dry Mouth  1  2/10 (20.00%)  2 0/10 (0.00%)  0
Nausea  1  0/10 (0.00%)  0 1/10 (10.00%)  1
General disorders     
Unpleasant Taste   4/10 (40.00%)  5 2/10 (20.00%)  2
Burning at infusion site * 1  0/10 (0.00%)  0 1/10 (10.00%)  1
Feeling Hot  1  4/10 (40.00%)  5 6/10 (60.00%)  7
Headache  1  2/10 (20.00%)  3 5/10 (50.00%)  6
Puncture Site Pain  1  2/10 (20.00%)  2 3/10 (30.00%)  3
Injury, poisoning and procedural complications     
Injection pressure sensation  1  0/10 (0.00%)  0 1/10 (10.00%)  1
Laceration  1  1/10 (10.00%)  1 0/10 (0.00%)  0
Vasovagal reaction  1  0/10 (0.00%)  0 1/10 (10.00%)  1
Vasovagal syncope  1  1/10 (10.00%)  1 0/10 (0.00%)  0
Venipuncture site bruising  1  1/10 (10.00%)  1 3/10 (30.00%)  4
Metabolism and nutrition disorders     
Decreased appetite  1  0/10 (0.00%)  0 2/10 (20.00%)  3
Musculoskeletal and connective tissue disorders     
Back Pain   1/10 (10.00%)  1 1/10 (10.00%)  1
Musculoskeletal pain  1  0/10 (0.00%)  0 2/10 (20.00%)  2
Pain in extremity  1  2/10 (20.00%)  2 2/10 (20.00%)  2
Plantar fasciitis  1  1/10 (10.00%)  1 0/10 (0.00%)  0
Nervous system disorders     
Burning sensation * 1  1/10 (10.00%)  3 0/10 (0.00%)  0
Paraesthesia  1  1/10 (10.00%)  1 3/10 (30.00%)  4
Psychiatric disorders     
Nervousness  1  0/10 (0.00%)  0 1/10 (10.00%)  1
Somnolence  1  2/10 (20.00%)  2 2/10 (20.00%)  3
Reproductive system and breast disorders     
Menstruation with increased bleeding  1  0/10 (0.00%)  0 1/10 (10.00%)  1
Respiratory, thoracic and mediastinal disorders     
Respiratory tract infection  1  2/10 (20.00%)  2 2/10 (20.00%)  2
Skin and subcutaneous tissue disorders     
Rash  1  1/10 (10.00%)  1 3/10 (30.00%)  4
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (12.0)
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. John Winkelman, MD, PhD
Organization: Brigham and Women's Hospital
Phone: 617-278-0061
Publications:
Buxton OM, Spiegel K and Van Cauter E. Modulation of endocrine function and metabolism by sleep and sleep loss. In: Sleep Medicine, edited by Lee-Chiong M, Carskadon M and Sateia M. Philadelphia: Hanley & Belfus, Inc., 2002, p. 59-69.
Czeisler CA, Winkelman JW and Richardson GS. Disorders of sleep and circadian rhythms. In: Harrison's Principles of Internal Medicine, edited by Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL and Jameson JL. New York: McGraw-Hill,Inc., 2000, p. 1-78.
Dinges DF, Kribbs NB, Bates BL and Carlin MM. A very brief probed-recall memory task: Sensitivity to sleep loss. Sleep Res 22: 330, 1993.
Dinges DF and Powell JW. Microcomputer analyses of performance on a portable, simple visual RT task during sustained operations. Behavior Research Methods, Instruments & Computers 17: 652-655, 1985.
Hoddes E, Dement WC and Zarcone V. The development and use of the Stanford Sleepiness Scale (SSS). Psychophysiol 9: 150, 1971.
Responsible Party: John W. Winkelman, MD, PhD, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT00555750     History of Changes
Other Study ID Numbers: BWH-HRC-2005-P-001997
ESRC0004 ( Other Grant/Funding Number: Sunovion previously Sepracor Inc )
M01RR002635 ( U.S. NIH Grant/Contract )
First Submitted: November 7, 2007
First Posted: November 9, 2007
Results First Submitted: May 21, 2013
Results First Posted: September 25, 2013
Last Update Posted: December 10, 2013