Chronic Sleep Deprivation as a Risk Factor for Metabolic Syndrome and Obesity
Chronic Sleep Deprivation as a Risk Factor for Metabolic Syndrome and Obesity
OBJECTIVE: Obesity and chronic sleep deprivation have both become increasingly pervasive
 medical problems in recent years. The prevalence of adult obesity has doubled over the past
 30 years and continues to increase. In addition, industrial societies attach an economic
 value to maximizing the waking period to the longest tolerable limit by sleeping as little as
 possible. Average sleep time has decreased over the last century by 2 hours. Chronically
 sleeping less has been associated with increased weight, endocrine and metabolic health risks
 including glucose intolerance, cardiovascular disease, and mortality. The possibility that
 the current epidemic of obesity and metabolic health risks may be partially related to
 insufficient sleep is now being recognized. The objective of this proof-of-concept controlled
 trial is to investigate the impact of increasing sleep time in chronically sleep-deprived,
 obese subjects.

 STUDY POPULATION: 18-50 year old, obese (BMI 30-50) men and premenopausal women, chronically
 sleep deprived, recruited from the Baltimore-Washington metropolitan area. Chronic sleep
 deprivation will be verified by the use of sleep logs and the use of actigraphy before entry
 into the study. Secondary causes of sleep deprivation such as insomnia, psychological
 (depression), and medical conditions associated with poor sleep quality (including
 obstructive sleep apnea) will be exclusionary criteria.

 DESIGN: This is a randomized, 12-month duration, comparison-controlled clinical trial of an
 extension of sleep up to approximately 7 hours and 30 minutes (Intervention Group) or
 continuation of habitual short sleep schedule (Comparison Group). The proposed treatment is
 an educational and behavioral intervention aimed at increasing sleep in a non-pharmacological
 fashion. The main analysis of the study will be to determine if additional sleep will result
 in a significant difference in body weight at the end of 12 months between the Intervention
 Group and the Comparison Group. In addition, we would like to establish whether 12 months of
 additional sleep will result in: a) a decreased prevalence of metabolic syndrome; and b)
 changes in the endocrine profile (i.e. inducing changes in leptin [increase] and ghrelin
 [decrease] opposite to the changes associated with chronic sleep deprivation). At the end of
 the 12-month intervention study (Phase 1, Efficacy Randomized Phase Study), all participants
 will be given information about the potential benefit of more sleep and encouraged to
 increase sleep time. Health teaching about proper nutrition and adequate exercise will also
 be provided at that time to the Intervention and Comparison Groups. All participants will be
 evaluated 6 months later to assess the effects of this intervention in a real-life situation,
 and offered participation in a three-year extension with semi-annual visits (Phase 2,
 Effectiveness 3 Year Follow-Up Phase Study), for which matched external comparison subjects
 will also be recruited ad hoc.

 OUTCOME PARAMETERS: body weight, average number of hours of sleep/night, fasting glucose and
 insulin, oral glucose tolerance test, leptin, ghrelin, adiponectin, other relevant endocrine
 and anthropometric measures, body composition, various metabolic parameters, food intake,
 energy expenditure, and quality of life measures.
OBJECTIVE: Obesity and chronic sleep deprivation have both become increasingly pervasive
 medical problems in recent years. The prevalence of adult obesity has doubled over the past
 30 years and continues to increase. In addition, industrial societies attach an economic
 value to maximizing the waking period to the longest tolerable limit by sleeping as little as
 possible. Average sleep time has decreased over the last century by 2 hours. Chronically
 sleeping less has been associated with increased weight, endocrine and metabolic health risks
 including glucose intolerance, cardiovascular disease, and mortality. The possibility that
 the current epidemic of obesity and metabolic health risks may be partially related to
 insufficient sleep is now being recognized. The objective of this proof-of-concept controlled
 trial is to investigate the impact of increasing sleep time in chronically sleep-deprived,
 obese subjects.

 STUDY POPULATION: 18-50 year old, obese (BMI 29-55) men and premenopausal women, chronically
 sleep deprived, recruited from the Baltimore-Washington metropolitan area. Chronic sleep
 deprivation will be verified by the use of sleep logs and the use of actigraphy before entry
 into the study. Secondary causes of sleep deprivation such as insomnia, psychological
 (depression), and medical conditions associated with poor sleep quality (including
 obstructive sleep apnea) will be exclusionary criteria.

 DESIGN: This is a randomized, 12-month duration, comparison-controlled clinical trial of an
 extension of sleep up to approximately 7 hours and 30 minutes (Intervention Group) or
 continuation of habitual short sleep schedule (Comparison Group). The proposed treatment is
 an educational and behavioral intervention aimed at increasing sleep in a non-pharmacological
 fashion. The main analysis of the study will be to determine if additional sleep will result
 in a significant difference in body weight at the end of 12 months between the Intervention
 Group and the Comparison Group. In addition, we would like to establish whether 12 months of
 additional sleep will result in: a) a decreased prevalence of metabolic syndrome; and b)
 changes in the endocrine profile (i.e. inducing changes in leptin [increase] and ghrelin
 [decrease] opposite to the changes associated with chronic sleep deprivation). At the end of
 the 12-month intervention study (Phase 1, Efficacy [Randomized Phase] Study), all
 participants will be given information about the potential benefit of more sleep and
 encouraged to increase sleep time. Health teaching about proper nutrition and adequate
 exercise will also be provided at that time to the Intervention and Comparison Groups. All
 participants will be evaluated 6 months later to assess the effects of this intervention in a
 real-life situation, and offered participation in a three-year extension with semi-annual
 visits (Phase 2, Effectiveness [3 Year Follow-Up Phase] Study), for which matched external
 comparison subjects will also be recruited ad hoc.

 OUTCOME PARAMETERS: body weight, average number of hours of sleep/night, fasting glucose and
 insulin, oral glucose tolerance test, leptin, ghrelin, adiponectin, other relevant endocrine
 and anthropometric measures, body composition, various metabolic parameters, food intake,
 energy expenditure, and quality of life measures.

 The study was terminated early for reasons of apparent futility of continuing accrual of
 participants according to the original study plan. The decision was based on independent
 analysis of data acquired during the initial feasibility phase and from interim analysis of
 early results that failed to document objectively the achievement of substantive and
 meaningful differences between experimental and control groups with respect to amounts of
 sleep extension, changes in metabolic parameters, or changes in weight. Feasibilities of
 achieving objective and substantive differences in these parameters were integral to the
 methodology of the original study plan and required to meet the statistical power
 calculations for the controlled trial.
-  INCLUSION CRITERIA:

 18 to 50 year old obese men and premenopausal women

 BMI between 29-55

 Chronically (for more than 6 months) sleep-deprived, defined as sleeping on a regular basis
 less than or equal to approximately 6-1/2 hours/night by history and objective devices
 (wrist activity monitors and sleep logs).

 INCLUSION CRITERIA: External comparison subjects for extension of Effectiveness Study must
 meet the criteria above.

 EXCLUSION CRITERIA:

 Diagnosed sleep disorders including:

 -  Chronic insomnia

 -  Untreated sleep disordered breathing (sleep apnea at a level of severity [using
 standardized criteria for measurement], or diagnosed UARS [upper airway resistance
 syndrome] that would impair the ability to increase sleep duration [Intervention
 Group] or maintain sleep duration [Comparison Group]. CPAP treatment that has been in
 place for 3 months or more and improves sleep is acceptable).

 -  Restless leg syndrome or periodic limb movement disorder

 -  Parasomnias (including REM sleep behavior disorders, confusional arousals, sleep
 terrors, sleepwalking, sleep violence)

 -  Primary bruxism is allowed as long as it does not interfere with the ability to sleep
 an additional 90 minutes a night

 -  Narcolepsy

 -  Central apnea.

 Unstable weight (voluntary losses in BMI greater than 5% over the past 6 months); currently
 being enrolled in a weight loss program

 Untreated or uncontrolled diabetes

 Severe uncontrolled hypertension

 Other chronic organ disease diagnosis including:

 -  COPD

 -  Chronic cardiac arrhythmia requiring treatments

 -  Gastro-esophageal disorders associated with sleep-related symptoms.

 Medications

 -  chronic use of prescription or over-the-counter medications known to affect sleep
 (e.g., systemic steroids, NSAIDs)

 -  current anticonvulsant therapy

 Chronic fatigue syndrome and fibromyalgia

 Acromegaly, hypothyroidism (unless on a stable replacement dose of thyroid hormone),
 Cushing disease or other endocrine disorders known to affect sleep

 Poorly controlled major depression (subjects who have been on a stable pharmacological
 antidepressant treatment for 3 months and are in remission without substantial weight gain
 are eligible).

 Other current DSM-IV diagnoses, including:

 -  Eating disorders such as bulimia nervosa and binge eating disorder

 -  Anxiety disorders such as PTSD and panic attacks

 -  Mania

 -  Schizophrenia.

 Medication and substance abuse such as excessive alcohol consumption or drug abuse or
 dependence that may pose a threat to compliance

 Being a rotating worker, shift worker (working evenings or nights), or long distance
 commuter (more than approximately 90 minutes each way), traveling frequently outside of
 time zone; being in an occupation that may require special vigilance such as driving a
 truck, bus, or cab; operating heavy machinery; being a pilot or air traffic controller

 Being likely to move to a different geographical area during the study

 Having a sleep partner that would make compliance with study requirements difficult

 Pregnancy and lactation

 Menopause

 Chronic excessive caffeine use (habitual intake of more than 500 mg/day)

 Any condition that in the opinion of the principal investigator makes study participation
 and compliance problematic.