Clinical trial NCT00555750: 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
Overall status: COMPLETED
Phase: NA
Conditions: Primary Insomnia
Keywords: sleep
metabolism
insulin
glucose
actigraphy
diary
volumetry
GABA
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Sumitomo Pharma America, Inc.
name: Mclean Hospital
name: National Center for Research Resources (NCRR)
First posted: 2007-11-09
Enrollment: 20
Sex: ALL
Minimum age (years): 25
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Change in Glucose Tolerance (Kg) in Response to Insulin-modified Intravenous Glucose Tolerance Test
timeFrame: baseline and 2 months post-treatment
Secondary outcomes:
measure: Acute Insulin Response to Glucose (AIRg)
timeFrame: baseline and 2 months post-treatment
measure: Change in Insulin Sensitivity (SI)
timeFrame: baseline and 2 months post-treatment
measure: Change in Glucose Effectiveness (SG)
timeFrame: baseline and 2 months post-treatment
measure: Change in HbA1c Levels
timeFrame: baseline and 2 months post-treatment
measure: Pre-Treatment Leptin Levels
timeFrame: baseline
measure: Post-treatment Leptin Levels
timeFrame: two months post-treatment
measure: Pre-treatment Ghrelin Levels
timeFrame: baseline
measure: Post-treatment Ghrelin Levels
timeFrame: 2 months post-treatment
measure: Change in Subjective Sleepiness as Measured on the Karolinska Sleepiness Scale (KSS)
timeFrame: baseline and 2 months post-treatment
measure: Change in Mean Lapses of Attention
timeFrame: baseline and 2 months post-treatment
measure: Change in Total Sleep Time as Reported in Sleep Diaries
timeFrame: baseline and 2 months post-treatment
measure: Change in Total Sleep Time Measured by PSG
timeFrame: baseline and 2 months post-treatment
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital, Division of Sleep Medicine
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: John W Winkelman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ayas NT, White DP, Al-Delaimy WK, Manson JE, Stampfer MJ, Speizer FE, Patel S, Hu FB. A prospective study of self-reported sleep duration and incident diabetes in women. Diabetes Care. 2003 Feb;26(2):380-4. doi: 10.2337/diacare.26.2.380.
citation: Ayas NT, White DP, Manson JE, Stampfer MJ, Speizer FE, Malhotra A, Hu FB. A prospective study of sleep duration and coronary heart disease in women. Arch Intern Med. 2003 Jan 27;163(2):205-9. doi: 10.1001/archinte.163.2.205.
citation: Beck-Nielsen H, Henriksen JE, Alford F, Hother-Nielson O. In vivo glucose metabolism, insulin secretion and, insulin action in Europids with non-insulin-dependent diabetes mellitus (NIDDM) and their first-degree relatives. Diabet Med. 1996 Sep;13(9 Suppl 6):S78-84.
citation: Belenky G, Wesensten NJ, Thorne DR, Thomas ML, Sing HC, Redmond DP, Russo MB, Balkin TJ. Patterns of performance degradation and restoration during sleep restriction and subsequent recovery: a sleep dose-response study. J Sleep Res. 2003 Mar;12(1):1-12. doi: 10.1046/j.1365-2869.2003.00337.x.
citation: Boyne MS, Saudek CD. Effect of insulin therapy on macrovascular risk factors in type 2 diabetes. Diabetes Care. 1999 Apr;22 Suppl 3:C45-53.
citation: 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.
citation: Buysse DJ, Jarrett DB, Miewald JM, Kupfer DJ, Greenhouse JB. Minute-by-minute analysis of REM sleep timing in major depression. Biol Psychiatry. 1990 Nov 15;28(10):911-25. doi: 10.1016/0006-3223(90)90571-i.
citation: 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.
citation: Dijk DJ, Duffy JF, Czeisler CA. Circadian and sleep/wake dependent aspects of subjective alertness and cognitive performance. J Sleep Res. 1992 Jun;1(2):112-7. doi: 10.1111/j.1365-2869.1992.tb00021.x.
citation: 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.
citation: 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.
citation: Gillberg M, Kecklund G, Akerstedt T. Relations between performance and subjective ratings of sleepiness during a night awake. Sleep. 1994 Apr;17(3):236-41. doi: 10.1093/sleep/17.3.236.
citation: Gottlieb DJ, Punjabi NM, Newman AB, Resnick HE, Redline S, Baldwin CM, Nieto FJ. Association of sleep time with diabetes mellitus and impaired glucose tolerance. Arch Intern Med. 2005 Apr 25;165(8):863-7. doi: 10.1001/archinte.165.8.863.
citation: Hoddes E, Dement WC and Zarcone V. The development and use of the Stanford Sleepiness Scale (SSS). Psychophysiol 9: 150, 1971.
citation: King H, Aubert RE, Herman WH. Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998 Sep;21(9):1414-31. doi: 10.2337/diacare.21.9.1414.
citation: King H, Zimmet P. Trends in the prevalence and incidence of diabetes: non-insulin-dependent diabetes mellitus. World Health Stat Q. 1988;41(3-4):190-6.
citation: Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, Salonen JT. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA. 2002 Dec 4;288(21):2709-16. doi: 10.1001/jama.288.21.2709.
citation: Nilsson PM, Roost M, Engstrom G, Hedblad B, Berglund G. Incidence of diabetes in middle-aged men is related to sleep disturbances. Diabetes Care. 2004 Oct;27(10):2464-9. doi: 10.2337/diacare.27.10.2464.
citation: Simon GE, VonKorff M. Prevalence, burden, and treatment of insomnia in primary care. Am J Psychiatry. 1997 Oct;154(10):1417-23. doi: 10.1176/ajp.154.10.1417.
citation: Spiegel K, Leproult R, Van Cauter E. Impact of sleep debt on metabolic and endocrine function. Lancet. 1999 Oct 23;354(9188):1435-9. doi: 10.1016/S0140-6736(99)01376-8.
citation: Spiegel K, Tasali E, Penev P, Van Cauter E. Brief communication: Sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite. Ann Intern Med. 2004 Dec 7;141(11):846-50. doi: 10.7326/0003-4819-141-11-200412070-00008.
citation: Van Dongen HP, Maislin G, Mullington JM, Dinges DF. The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation. Sleep. 2003 Mar 15;26(2):117-26. doi: 10.1093/sleep/26.2.117.