Sleep Loss and Mechanisms of Impaired Glucose Metabolism

This study has been completed.
Sponsor:
Collaborators:
Sunovion
Mclean Hospital
Information provided by (Responsible Party):
John W. Winkelman, MD, PhD, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT00555750
First received: November 7, 2007
Last updated: November 15, 2013
Last verified: November 2013

November 7, 2007
November 15, 2013
March 2006
July 2008   (final data collection date for primary outcome measure)
Change in Glucose Tolerance (Kg) in Response to Insulin-modified Intravenous Glucose Tolerance Test [ Time Frame: baseline and 2 months post-treatment ] [ Designated as safety issue: No ]
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.
Glucose Tolerance in response to insulin-modified intravenous glucose tolerance test [ Time Frame: 2 months ]
Complete list of historical versions of study NCT00555750 on ClinicalTrials.gov Archive Site
  • Acute Insulin Response to Glucose (AIRg) [ Time Frame: baseline and 2 months post-treatment ] [ Designated as safety issue: No ]
    Change over two months in 1st phase Insulin secretion
  • Change in Insulin Sensitivity (SI) [ Time Frame: baseline and 2 months post-treatment ] [ Designated as safety issue: No ]

    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) [ Time Frame: baseline and 2 months post-treatment ] [ Designated as safety issue: No ]

    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 [ Time Frame: baseline and 2 months post-treatment ] [ Designated as safety issue: No ]
    Difference in HbA1c levels following two months treatment with eszopiclone versus placebo
  • Pre-Treatment Leptin Levels [ Time Frame: baseline ] [ Designated as safety issue: No ]
    Leptin Levels prior to two months treatment with eszopiclone or placebo, measure after an overnight fast
  • Post-treatment Leptin Levels [ Time Frame: two months post-treatment ] [ Designated as safety issue: No ]
    Leptin levels following two months treatment with 3mg eszopiclone or placebo, measured after an overnight fast
  • Pre-treatment Ghrelin Levels [ Time Frame: baseline ] [ Designated as safety issue: No ]
    Ghrelin levels prior to two months treatment with 3mg eszopiclone or placebo, measured after an overnight fast
  • Post-treatment Ghrelin Levels [ Time Frame: 2 months post-treatment ] [ Designated as safety issue: No ]
    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) [ Time Frame: baseline and 2 months post-treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: baseline and 2 months post-treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: baseline and 2 months post-treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: baseline and 2 months post-treatment ] [ Designated as safety issue: No ]
    Change (baseline minus post-treatment) in total sleep time measured by polysomnography after two months treatment with 3mg eszopiclone or placebo
1st phase Insulin secretion, Insulin sensitivity, glucose effectiveness; HbA1c levels; Leptin, Ghrelin levels; Alertness, Performance markers; Actigraphy, diary, and PSG of sleep/wake; hippocampal volumetry; Brain GABA levels by MR Spectroscopy [ Time Frame: 2 months ]
Not Provided
Not Provided
 
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

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

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.

Interventional
Not Provided
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Primary Insomnia
  • Drug: eszopiclone
    3mg tablet, by mouth nightly 30 min before bed, for two months
    Other Name: Lunesta
  • Drug: placebo
    inactive placebo tablet, by mouth nightly 30 minutes before bed, for two months
  • Experimental: eszopiclone (3mg)
    active medication (eszopiclone 3mg tablet) by mouth nightly 30 min before bed
    Intervention: Drug: eszopiclone
  • Placebo Comparator: placebo
    identical placebo tablet by mouth nightly 30 min before bed
    Intervention: Drug: placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
20
August 2008
July 2008   (final data collection date for primary outcome measure)

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
Both
25 Years to 55 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00555750
BWH-HRC-2005-P-001997, ESRC0004, M01RR002635
No
John W. Winkelman, MD, PhD, Brigham and Women's Hospital
Brigham and Women's Hospital
  • Sunovion
  • Mclean Hospital
  • National Center for Research Resources (NCRR)
Principal Investigator: John W Winkelman, MD, PhD Brigham and Women's Hospital
Brigham and Women's Hospital
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP