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Sleep Loss and Mechanisms of Impaired Glucose Metabolism

Primary Purpose

Primary Insomnia

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
eszopiclone
placebo
Sponsored by
Brigham and Women's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Primary Insomnia focused on measuring sleep, metabolism, insulin, glucose, actigraphy, diary, volumetry, GABA

Eligibility Criteria

25 Years - 55 Years (Adult)All SexesDoes not accept 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

Sites / Locations

  • Brigham and Women's Hospital, Division of Sleep Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

eszopiclone (3mg)

placebo

Arm Description

active medication (eszopiclone 3mg tablet) by mouth nightly 30 min before bed

identical placebo tablet by mouth nightly 30 min before bed

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Acute Insulin Response to Glucose (AIRg)
Change over two months in 1st phase Insulin secretion
Change in Insulin Sensitivity (SI)
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)
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
Difference in HbA1c levels following two months treatment with eszopiclone versus placebo
Pre-Treatment Leptin Levels
Leptin Levels prior to two months treatment with eszopiclone or placebo, measure after an overnight fast
Post-treatment Leptin Levels
Leptin levels following two months treatment with 3mg eszopiclone or placebo, measured after an overnight fast
Pre-treatment Ghrelin Levels
Ghrelin levels prior to two months treatment with 3mg eszopiclone or placebo, measured after an overnight fast
Post-treatment Ghrelin Levels
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)
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
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
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
Change (baseline minus post-treatment) in total sleep time measured by polysomnography after two months treatment with 3mg eszopiclone or placebo

Full Information

First Posted
November 7, 2007
Last Updated
November 15, 2013
Sponsor
Brigham and Women's Hospital
Collaborators
Sumitomo Pharma America, Inc., Mclean Hospital, National Center for Research Resources (NCRR)
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1. Study Identification

Unique Protocol Identification Number
NCT00555750
Brief Title
Sleep Loss and Mechanisms of Impaired Glucose Metabolism
Official Title
The Effects of Eszopiclone Treatment (3mg for Two Months) to Counteract the Adverse Metabolic Consequences of Primary Insomnia
Study Type
Interventional

2. Study Status

Record Verification Date
November 2013
Overall Recruitment Status
Completed
Study Start Date
March 2006 (undefined)
Primary Completion Date
July 2008 (Actual)
Study Completion Date
August 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital
Collaborators
Sumitomo Pharma America, Inc., Mclean Hospital, National Center for Research Resources (NCRR)

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Insomnia
Keywords
sleep, metabolism, insulin, glucose, actigraphy, diary, volumetry, GABA

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
eszopiclone (3mg)
Arm Type
Experimental
Arm Description
active medication (eszopiclone 3mg tablet) by mouth nightly 30 min before bed
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
identical placebo tablet by mouth nightly 30 min before bed
Intervention Type
Drug
Intervention Name(s)
eszopiclone
Other Intervention Name(s)
Lunesta
Intervention Description
3mg tablet, by mouth nightly 30 min before bed, for two months
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
inactive placebo tablet, by mouth nightly 30 minutes before bed, for two months
Primary Outcome Measure Information:
Title
Change in Glucose Tolerance (Kg) in Response to Insulin-modified Intravenous Glucose Tolerance Test
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
Secondary Outcome Measure Information:
Title
Acute Insulin Response to Glucose (AIRg)
Description
Change over two months in 1st phase Insulin secretion
Time Frame
baseline and 2 months post-treatment
Title
Change in Insulin Sensitivity (SI)
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
Title
Change in Glucose Effectiveness (SG)
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
Title
Change in HbA1c Levels
Description
Difference in HbA1c levels following two months treatment with eszopiclone versus placebo
Time Frame
baseline and 2 months post-treatment
Title
Pre-Treatment Leptin Levels
Description
Leptin Levels prior to two months treatment with eszopiclone or placebo, measure after an overnight fast
Time Frame
baseline
Title
Post-treatment Leptin Levels
Description
Leptin levels following two months treatment with 3mg eszopiclone or placebo, measured after an overnight fast
Time Frame
two months post-treatment
Title
Pre-treatment Ghrelin Levels
Description
Ghrelin levels prior to two months treatment with 3mg eszopiclone or placebo, measured after an overnight fast
Time Frame
baseline
Title
Post-treatment Ghrelin Levels
Description
Ghrelin levels following two months treatment with 3mg eszopiclone or placebo, measured after an overnight fast
Time Frame
2 months post-treatment
Title
Change in Subjective Sleepiness as Measured on the Karolinska Sleepiness Scale (KSS)
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
Title
Change in Mean Lapses of Attention
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
Title
Change in Total Sleep Time as Reported in Sleep Diaries
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
Title
Change in Total Sleep Time Measured by PSG
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John W Winkelman, MD, PhD
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hospital, Division of Sleep Medicine
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

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Sleep Loss and Mechanisms of Impaired Glucose Metabolism

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