Obesity and chronic sleep deprivation have both become increasingly pervasive medical problems in recent years. Average sleep time has decreased over the last century by two hours. Chronically sleeping less has been associated with increased weight, various endocrine changes such as an increase in cortisol levels, a decrease in growth hormone levels and changes in the adypocite-derived hormone leptin and the gastric produced hormone ghrelin that, together may increase appetite and food intake. Immune alterations associated with obesity and sleep deprivation include subclinical inflammation, and a decreased resistance to infections, respectively. We have recently demonstrated that increased weight in subjects suffering from sleep disturbances and depression is associated with an increase in proinflammatory cytokines and with a decreased in anti-inflammatory cytokines. Such changes are detectable in the serum as well as in the sweat, as non invasively collected over 24h by the means of a sweat patch, specifically developed by us to study endocrine immune relationships in freely living subjects. The general goal of this proof-of-concept, controlled trial is to investigate the impact of increasing sleep time on endocrine and immune parameters in chronically sleep-deprived, obese subjects. STUDY POPULATION: 18 to 50 year old, obese (BMI 30-55) men and premenopausal women, who usually sleep less than 6 hours, mainly recruited from the Baltimore-Washington metropolitan area. Sleep duration will be assessed by the use of sleep logs and actigraphy. 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 sleep extension (Intervention Group) or continuation of habitual short sleep schedule (Comparison Group). The 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 changes in the endocrine and immune profiles opposite to those associated with chronic sleep deprivation. Specifically, we hypothesize that 12 months of sleep extension will result in weight loss and subsequent corrections in the following hormonal levels: leptin, adiponectin, ghrelin, cortisol, and growth hormones, among others. The immune and inflammatory profile will be characterized by a decrease in C-reactive protein, TNF-alpha, IL-6 and other inflammatory cytokines, and a return of anti-inflammatory cytokines to a healthy range. At the end of the 12-month intervention study (Phase 1, Efficacy 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 Comparison Group. All participants will be evaluated 6 months later to assess the effects of this intervention in a real-life situation (Phase 2, Effectiveness Study). As of September 6 2012, 126 subjects have been randomized. Two third of the participants are women and ore than 50% are minoritites. Subjects'retention in this prospective study has been excellent with less than 15% of subjects interrupting the study before completion. Most common reasons for interruption include move to a different geographical area and the clinical need for bariatric surgery or the need for drastic change sin life style (diet, physical exercise) above and beyond the standard of care. OUTCOME PARAMETERS: body weight, food intake, hormones, and cytokines.

Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2013
Total Cost
$200,997
Indirect Cost
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State
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Lucassen, Eliane A; Zhao, Xiongce; Rother, Kristina I et al. (2013) Evening chronotype is associated with changes in eating behavior, more sleep apnea, and increased stress hormones in short sleeping obese individuals. PLoS One 8:e56519
de Jonge, Lilian; Zhao, Xiongce; Mattingly, Megan S et al. (2012) Poor sleep quality and sleep apnea are associated with higher resting energy expenditure in obese individuals with short sleep duration. J Clin Endocrinol Metab 97:2881-9
Knutson, Kristen L; Zhao, Xiongce; Mattingly, Megan et al. (2012) Predictors of sleep-disordered breathing in obese adults who are chronic short sleepers. Sleep Med 13:484-9
Lucassen, Eliane A; Cizza, Giovanni (2012) The Hypothalamic-Pituitary-Adrenal Axis, Obesity, and Chronic Stress Exposure: Sleep and the HPA Axis in Obesity. Curr Obes Rep 1:208-215
Cizza, Giovanni; Rother, Kristina I (2011) Was Feuerbach right: are we what we eat? J Clin Invest 121:2969-71
Knutson, Kristen L; Galli, Giulia; Zhao, Xiongce et al. (2011) No association between leptin levels and sleep duration or quality in obese adults. Obesity (Silver Spring) 19:2433-5
Cizza, G; Requena, M; Galli, G et al. (2011) Chronic sleep deprivation and seasonality: implications for the obesity epidemic. J Endocrinol Invest 34:793-800
Cizza, Giovanni; Marincola, Paula; Mattingly, Megan et al. (2010) Treatment of obesity with extension of sleep duration: a randomized, prospective, controlled trial. Clin Trials 7:274-85
Cizza, Giovanni; Nguyen, Vi T; Eskandari, Farideh et al. (2010) Low 24-hour adiponectin and high nocturnal leptin concentrations in a case-control study of community-dwelling premenopausal women with major depressive disorder: the Premenopausal, Osteopenia/Osteoporosis, Women, Alendronate, Depression (POWER) study. J Clin Psychiatry 71:1079-87
Cizza, G; Primma, S; Coyle, M et al. (2010) Depression and osteoporosis: a research synthesis with meta-analysis. Horm Metab Res 42:467-82

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