Trial Outcomes & Findings for Sleep Loss and Mechanisms of Impaired Glucose Metabolism (NCT NCT00555750)

NCT ID: NCT00555750

Last Updated: 2013-12-10

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

20 participants

Primary outcome timeframe

baseline and 2 months post-treatment

Results posted on

2013-12-10

Participant Flow

Participant milestones

Participant milestones
Measure
Eszopiclone
nightly active medication (eszopiclone, 3 mg tablet) oral administration \~30 min before bed
Placebo
nightly placebo (identical tablet to active medication) oral administration \~30 min before bed
Overall Study
STARTED
10
10
Overall Study
COMPLETED
10
10
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Sleep Loss and Mechanisms of Impaired Glucose Metabolism

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Active
n=10 Participants
active medication administration nightly before bed
Placebo
n=10 Participants
nightly administration of placebo before bed
Total
n=20 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
10 Participants
n=5 Participants
10 Participants
n=7 Participants
20 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Sex: Female, Male
Female
2 Participants
n=5 Participants
7 Participants
n=7 Participants
9 Participants
n=5 Participants
Sex: Female, Male
Male
8 Participants
n=5 Participants
3 Participants
n=7 Participants
11 Participants
n=5 Participants
Region of Enrollment
United States
10 participants
n=5 Participants
10 participants
n=7 Participants
20 participants
n=5 Participants

PRIMARY outcome

Timeframe: baseline and 2 months post-treatment

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.

Outcome measures

Outcome measures
Measure
Active
n=10 Participants
active medication administration nightly before bed
Placebo
n=10 Participants
nightly administration of placebo before bed
Change in Glucose Tolerance (Kg) in Response to Insulin-modified Intravenous Glucose Tolerance Test
.33 %/min, slope of natural log glucose
Standard Deviation .94
-0.10 %/min, slope of natural log glucose
Standard Deviation .42

SECONDARY outcome

Timeframe: baseline and 2 months post-treatment

Change over two months in 1st phase Insulin secretion

Outcome measures

Outcome measures
Measure
Active
n=10 Participants
active medication administration nightly before bed
Placebo
n=10 Participants
nightly administration of placebo before bed
Acute Insulin Response to Glucose (AIRg)
94.0 mU*l^-1*min
Standard Deviation 269.0
25.1 mU*l^-1*min
Standard Deviation 74.7

SECONDARY outcome

Timeframe: baseline and 2 months post-treatment

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)

Outcome measures

Outcome measures
Measure
Active
n=10 Participants
active medication administration nightly before bed
Placebo
n=10 Participants
nightly administration of placebo before bed
Change in Insulin Sensitivity (SI)
-1.19 mU/l)^-1*min^-1
Standard Deviation 2.57
0.05 mU/l)^-1*min^-1
Standard Deviation 3.43

SECONDARY outcome

Timeframe: baseline and 2 months post-treatment

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)

Outcome measures

Outcome measures
Measure
Active
n=10 Participants
active medication administration nightly before bed
Placebo
n=10 Participants
nightly administration of placebo before bed
Change in Glucose Effectiveness (SG)
0.001 min^-1
Standard Deviation 0.004
0.001 min^-1
Standard Deviation 0.009

SECONDARY outcome

Timeframe: baseline and 2 months post-treatment

Difference in HbA1c levels following two months treatment with eszopiclone versus placebo

Outcome measures

Outcome measures
Measure
Active
n=10 Participants
active medication administration nightly before bed
Placebo
n=10 Participants
nightly administration of placebo before bed
Change in HbA1c Levels
.03 percentage of glycosylation
Standard Error .11
-.09 percentage of glycosylation
Standard Error .06

SECONDARY outcome

Timeframe: baseline

Leptin Levels prior to two months treatment with eszopiclone or placebo, measure after an overnight fast

Outcome measures

Outcome measures
Measure
Active
n=10 Participants
active medication administration nightly before bed
Placebo
n=10 Participants
nightly administration of placebo before bed
Pre-Treatment Leptin Levels
4.99 ng/mL
Standard Deviation 3.63
16.53 ng/mL
Standard Deviation 11.37

SECONDARY outcome

Timeframe: two months post-treatment

Leptin levels following two months treatment with 3mg eszopiclone or placebo, measured after an overnight fast

Outcome measures

Outcome measures
Measure
Active
n=9 Participants
active medication administration nightly before bed
Placebo
n=10 Participants
nightly administration of placebo before bed
Post-treatment Leptin Levels
5.49 ng/mL
Standard Deviation 4.33
15.28 ng/mL
Standard Deviation 9.94

SECONDARY outcome

Timeframe: baseline

Ghrelin levels prior to two months treatment with 3mg eszopiclone or placebo, measured after an overnight fast

Outcome measures

Outcome measures
Measure
Active
n=10 Participants
active medication administration nightly before bed
Placebo
n=10 Participants
nightly administration of placebo before bed
Pre-treatment Ghrelin Levels
573.14 ng/mL
Standard Deviation 336.50
648.41 ng/mL
Standard Deviation 230.95

SECONDARY outcome

Timeframe: 2 months post-treatment

Ghrelin levels following two months treatment with 3mg eszopiclone or placebo, measured after an overnight fast

Outcome measures

Outcome measures
Measure
Active
n=9 Participants
active medication administration nightly before bed
Placebo
n=10 Participants
nightly administration of placebo before bed
Post-treatment Ghrelin Levels
544.95 ng/mL
Standard Deviation 273.65
670.94 ng/mL
Standard Deviation 180.36

SECONDARY outcome

Timeframe: baseline and 2 months post-treatment

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.

Outcome measures

Outcome measures
Measure
Active
n=10 Participants
active medication administration nightly before bed
Placebo
n=10 Participants
nightly administration of placebo before bed
Change in Subjective Sleepiness as Measured on the Karolinska Sleepiness Scale (KSS)
0.53 units on a scale
Standard Error 0.42
0.38 units on a scale
Standard Error 0.38

SECONDARY outcome

Timeframe: baseline and 2 months post-treatment

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.

Outcome measures

Outcome measures
Measure
Active
n=10 Participants
active medication administration nightly before bed
Placebo
n=10 Participants
nightly administration of placebo before bed
Change in Mean Lapses of Attention
-0.04 lapses of attention
Standard Error 0.49
0.07 lapses of attention
Standard Error 0.29

SECONDARY outcome

Timeframe: baseline and 2 months post-treatment

Total sleep time reported on sleep diaries prior to treatment with 3mg eszopiclone or placebo. Change defined as baseline minus post-treatment).

Outcome measures

Outcome measures
Measure
Active
n=9 Participants
active medication administration nightly before bed
Placebo
n=10 Participants
nightly administration of placebo before bed
Change in Total Sleep Time as Reported in Sleep Diaries
.58 hours
Standard Deviation .36
.09 hours
Standard Deviation .01

SECONDARY outcome

Timeframe: baseline and 2 months post-treatment

Change (baseline minus post-treatment) in total sleep time measured by polysomnography after two months treatment with 3mg eszopiclone or placebo

Outcome measures

Outcome measures
Measure
Active
n=10 Participants
active medication administration nightly before bed
Placebo
n=10 Participants
nightly administration of placebo before bed
Change in Total Sleep Time Measured by PSG
2.9 minutes
Standard Deviation 25.5
-6.4 minutes
Standard Deviation 30.2

Adverse Events

Active

Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Active
n=10 participants at risk
active medication administration nightly before bed
Placebo
n=10 participants at risk
nightly administration of placebo before bed
Gastrointestinal disorders
Abdominal Discomfort
10.0%
1/10 • Number of events 3
20.0%
2/10 • Number of events 2
Musculoskeletal and connective tissue disorders
Back Pain
10.0%
1/10 • Number of events 1
10.0%
1/10 • Number of events 1
General disorders
Unpleasant Taste
40.0%
4/10 • Number of events 5
20.0%
2/10 • Number of events 2
General disorders
Burning at infusion site
0.00%
0/10
10.0%
1/10 • Number of events 1
Nervous system disorders
Burning sensation
10.0%
1/10 • Number of events 3
0.00%
0/10
Gastrointestinal disorders
Constipation
10.0%
1/10 • Number of events 1
0.00%
0/10
Metabolism and nutrition disorders
Decreased appetite
0.00%
0/10
20.0%
2/10 • Number of events 3
Cardiac disorders
Dizziness
30.0%
3/10 • Number of events 3
20.0%
2/10 • Number of events 3
Gastrointestinal disorders
Dry Mouth
20.0%
2/10 • Number of events 2
0.00%
0/10
Skin and subcutaneous tissue disorders
Rash
10.0%
1/10 • Number of events 1
30.0%
3/10 • Number of events 4
Eye disorders
Eye irritation
10.0%
1/10 • Number of events 1
0.00%
0/10
General disorders
Feeling Hot
40.0%
4/10 • Number of events 5
60.0%
6/10 • Number of events 7
Respiratory, thoracic and mediastinal disorders
Respiratory tract infection
20.0%
2/10 • Number of events 2
20.0%
2/10 • Number of events 2
General disorders
Headache
20.0%
2/10 • Number of events 3
50.0%
5/10 • Number of events 6
Injury, poisoning and procedural complications
Injection pressure sensation
0.00%
0/10
10.0%
1/10 • Number of events 1
Injury, poisoning and procedural complications
Laceration
10.0%
1/10 • Number of events 1
0.00%
0/10
Reproductive system and breast disorders
Menstruation with increased bleeding
0.00%
0/10
10.0%
1/10 • Number of events 1
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
0.00%
0/10
20.0%
2/10 • Number of events 2
Gastrointestinal disorders
Nausea
0.00%
0/10
10.0%
1/10 • Number of events 1
Psychiatric disorders
Nervousness
0.00%
0/10
10.0%
1/10 • Number of events 1
Musculoskeletal and connective tissue disorders
Pain in extremity
20.0%
2/10 • Number of events 2
20.0%
2/10 • Number of events 2
Nervous system disorders
Paraesthesia
10.0%
1/10 • Number of events 1
30.0%
3/10 • Number of events 4
Musculoskeletal and connective tissue disorders
Plantar fasciitis
10.0%
1/10 • Number of events 1
0.00%
0/10
General disorders
Puncture Site Pain
20.0%
2/10 • Number of events 2
30.0%
3/10 • Number of events 3
Psychiatric disorders
Somnolence
20.0%
2/10 • Number of events 2
20.0%
2/10 • Number of events 3
Injury, poisoning and procedural complications
Vasovagal reaction
0.00%
0/10
10.0%
1/10 • Number of events 1
Injury, poisoning and procedural complications
Vasovagal syncope
10.0%
1/10 • Number of events 1
0.00%
0/10
Injury, poisoning and procedural complications
Venipuncture site bruising
10.0%
1/10 • Number of events 1
30.0%
3/10 • Number of events 4

Additional Information

Dr. John Winkelman, MD, PhD

Brigham and Women's Hospital

Phone: 617-278-0061

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place