Sleep Loss and Mechanisms of Impaired Glucose Metabolism

The Effects of Eszopiclone Treatment (3mg for Two Months) to Counteract the Adverse Metabolic Consequences of Primary Insomnia

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00555750

Enrollment

Registered

2007-11-09

Start date

2006-03-31

Completion date

2008-08-31

Last updated

2013-12-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Primary Insomnia

Keywords

sleep, metabolism, insulin, glucose, actigraphy, diary, volumetry, GABA

Brief summary

The purpose of this study is to test the effects of sleep and eszopiclone, a drug that helps people sleep, on how the body processes glucose (sugar). Eszopiclone is approved by the U.S. Food and Drug Administration (FDA) for sale for the treatment of insomnia. It is marketed in the United States as LUNESTA. Main Hypothesis: Primary insomnia is associated with impairments of glucose metabolism that can be reversed by two months of eszopiclone for the primary insomnia

Detailed description

Insomnia is the most common sleep disorder, affecting nearly one-third of all adults in any given year, and chronically affecting 10-15% of the adult population. Reduced sleep time, independent of insomnia, has been associated with a variety of deleterious long term effects, including an increased risk of incident myocardial infarction and symptomatic diabetes. Chronic partial sleep loss or insomnia may impair glucose metabolism in the short term and are associated with the development of diabetes in the long term. Although the extent of sleep loss is more acute in the laboratory-based 'sleep debt' studies of healthy volunteers, chronic primary insomnia patients exhibit 'hyperarousal' (hypercortisolemia in the afternoon and evening, accelerated metabolism) similar to that seen with acute sleep deprivation. In addition, degradations of sleep quantity and quality in primary insomnia have been attributed to cognitive and somatic hyperarousal in the sleep setting. study examines and quantifies in adult men and women the link between primary insomnia and impaired glucose tolerance. This study examines the extent which adequate treatment of primary insomnia reverses impairments of glucose metabolism. If abnormalities of glucose metabolism are reversible, this study will demonstrate the importance of treatment of chronic primary insomnia.

Interventions

DRUGeszopiclone

3mg tablet, by mouth nightly 30 min before bed, for two months

DRUGplacebo

inactive placebo tablet, by mouth nightly 30 minutes before bed, for two months

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

25 Years to 55 Years

Healthy volunteers

Inclusion criteria

* Age 25-55 * Complaint of insomnia of at least 6 months duration * DSM-IV diagnosis of Primary Insomnia * Sleep diary: mean Total Sleep Time \< 6 hours and a mean total wake time (sleep latency + wake after sleep onset) of greater than 60 minutes (in previous 14 days as recorded on sleep diary) * A willingness to comply with study procedures * If of child-bearing potential, using a medically-accepted method of birth control, including abstinence, barrier method with spermicide, steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method, and intrauterine device \[IUD\])

Exclusion criteria

* Current diagnosis of DSM-IV Axis I disorder other than Primary Insomnia * Regular treatment (more than 1 time/week) with CNS active medication within 1 month of fist inpatient visit * Treatment with medications that interfere with glucose metabolism including anti-diabetic medications or steroidal contraceptives * Uncontrolled medical illness that would interfere with participation in the study * Body Mass Index \>32 or \<19.8 * Current symptoms or diagnosis of any moderate to severe sleep disorder other than insomnia * No menopausal or peri-menopausal symptoms that disrupt sleep * Pregnant, lactating or planning to become pregnant * Consumption of \> 2 caffeinated beverages per day (including coffee, tea and/or other caffeine-containing beverages or food) during 3 weeks prior to the start of the study

Design outcomes

Primary

Measure	Time frame	Description
Change in Glucose Tolerance (Kg) in Response to Insulin-modified Intravenous Glucose Tolerance Test	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.

Secondary

Measure	Time frame	Description
Change in Insulin Sensitivity (SI)	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)
Change in Glucose Effectiveness (SG)	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)
Change in HbA1c Levels	baseline and 2 months post-treatment	Difference in HbA1c levels following two months treatment with eszopiclone versus placebo
Pre-Treatment Leptin Levels	baseline	Leptin Levels prior to two months treatment with eszopiclone or placebo, measure after an overnight fast
Post-treatment Leptin Levels	two months post-treatment	Leptin levels following two months treatment with 3mg eszopiclone or placebo, measured after an overnight fast
Acute Insulin Response to Glucose (AIRg)	baseline and 2 months post-treatment	Change over two months in 1st phase Insulin secretion
Post-treatment Ghrelin Levels	2 months post-treatment	Ghrelin levels following two months treatment with 3mg eszopiclone or placebo, measured after an overnight fast
Change in Subjective Sleepiness as Measured on the Karolinska Sleepiness Scale (KSS)	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.
Change in Mean Lapses of Attention	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.
Change in Total Sleep Time as Reported in Sleep Diaries	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).
Change in Total Sleep Time Measured by PSG	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
Pre-treatment Ghrelin Levels	baseline	Ghrelin levels prior to two months treatment with 3mg eszopiclone or placebo, measured after an overnight fast

Countries

United States

Participant flow

Participants by arm

Arm	Count
Active active medication administration nightly before bed	10
Placebo nightly administration of placebo before bed	10
Total	20

Baseline characteristics

Characteristic	Active	Placebo	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	10 Participants	10 Participants	20 Participants
Region of Enrollment United States	10 participants	10 participants	20 participants
Sex: Female, Male Female	2 Participants	7 Participants	9 Participants
Sex: Female, Male Male	8 Participants	3 Participants	11 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	10 / 10	10 / 10
serious Total, serious adverse events	0 / 10	0 / 10

Outcome results

Primary

Change in Glucose Tolerance (Kg) in Response to Insulin-modified Intravenous Glucose Tolerance Test

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.