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
  Purpose

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


Condition Intervention
Primary Insomnia
Drug: eszopiclone
Drug: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: The Effects of Eszopiclone Treatment (3mg for Two Months) to Counteract the Adverse Metabolic Consequences of Primary Insomnia

Resource links provided by NLM:


Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Enrollment: 20
Study Start Date: March 2006
Study Completion Date: August 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: eszopiclone (3mg)
active medication (eszopiclone 3mg tablet) by mouth nightly 30 min before bed
Drug: eszopiclone
3mg tablet, by mouth nightly 30 min before bed, for two months
Other Name: Lunesta
Placebo Comparator: placebo
identical placebo tablet by mouth nightly 30 min before bed
Drug: placebo
inactive placebo tablet, by mouth nightly 30 minutes before bed, for two months

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.

  Eligibility

Ages Eligible for Study:   25 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00555750

Locations
United States, Massachusetts
Brigham and Women's Hospital, Division of Sleep Medicine
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Brigham and Women's Hospital
Sunovion
Mclean Hospital
Investigators
Principal Investigator: John W Winkelman, MD, PhD Brigham and Women's Hospital
  More Information

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, Associate Professor of Psychiatry, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT00555750     History of Changes
Other Study ID Numbers: BWH-HRC-2005-P-001997, ESRC0004, M01RR002635
Study First Received: November 7, 2007
Results First Received: May 21, 2013
Last Updated: November 15, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Brigham and Women's Hospital:
sleep
metabolism
insulin
glucose
actigraphy
diary
volumetry
GABA

Additional relevant MeSH terms:
Sleep Initiation and Maintenance Disorders
Dyssomnias
Mental Disorders
Nervous System Diseases
Sleep Disorders
Sleep Disorders, Intrinsic
Eszopiclone
Central Nervous System Agents
Central Nervous System Depressants
Hypnotics and Sedatives
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014