Body Weight Regulation in Patients With Narcolepsy

INCLUSION CRITERIA: Patients -18 to 55 year old men and pre-menopausal women with current narcolepsy, otherwise healthy. Controls -18 to 55 year old healthy men and pre-menopausal women. SUBJECTS WITH NARCOLEPSY INCLUSION: Having a current diagnosis of narcolepsy with moderate or severe daytime sleepiness for at least 6 months, according to the International Classification of Sleep Disorder (ICSD). Both new and previously diagnosed patients are eligible. Females of childbearing potential must have a negative serum pregnancy test. A valid barrier contraception method is required over the duration of the study. Patients must agree to refrain from operating a motor vehicle and from being involved in any other potentially hazardous activity during the tapering off and the drug-free periods. SUBJECTS WITH NARCOLEPSY EXCLUSION: Pregnancy and lactation (women only) Use of birth control pills Menopause, defined as 6 consecutive months without mensis Clinical diagnosis of polycystic ovary disease, chronic history of anovulatory cycles or other alterations of the menstrual cycle (for women only) Use of any experimental drug or current participation in another research protocol Chronic amphetamines in the last 2 months and any drug known to influence the autonomic nervous system including appetite suppressants Excessive daytime sleepiness (EDS) related to: Sleep apnea Periodic limb movements Substance disorder or alcohol consumption Any concurrent psychiatric, neurological, neoplastic, endocrinologic, or infectious disease that may contribute to EDS Insufficient sleep (less than 6 hours/night) or any other known cause inducing sleepiness Working in an occupational environment that requires variable or routine night shifts History of head trauma or history of seizure Agitated state or severe anxiety, moderate or severe psychosis or dementia Current major depression (Hamilton score greater than 18), subjects currently receiving pharmacological treatment for depression (even if their Hamilton score is lower than 18), anyone who has or had suicidal ideation Dyskinesia or other neurological conditions Use of any medications that may influence sleep or contribute to EDS, except for anticataplectic medications, including: Hypnotic, anxiolytic, chronic amphetamine use, antidepressants, antihistamine, clonidine, anticonvulsants Hyperthyroidism or hypothyroidism Symptomatic cardiac disease For those subjects consenting to the exercise test (Cooper test) Any medical contraindication to exercise of moderate intensity and short duration including cardiovascular or respiratory conditions, morbid obesity, and severe osteoarthritis of the lower extremities Chronic illicit drug use Use of antipsychotic drugs Narcoleptic subjects with coexistent significant sleep apnea or respiratory disturbances are excluded Major cardiac rhythm disturbances, respiratory rate alterations, or any other major organ disease that would make the interpretation of HRV data arduous Fever EXCLUSION RELATED TO THE METABOLIC STATUS: Weight fluctuations defined as increase or decrease in body weight greater than 5% over the last 3 months Unstable physical activity in the 3 months prior to study entry Any secondary cause of obesity, including: Cushing syndrome, hypothyroidism, GH and testosterone deficiency, polycystic ovarian syndrome, insulinoma, hypothalamic lesions, and genetic obesity syndromes such as Prader-Willy and other genetic syndromes Obesity-related medical conditions requiring pharmacological treatment Insulin-dependent diabetes mellitus Uncontrolled hypertension Uncontrolled hyperlipidemia Current smoking, defined as more than 2 cigarettes/day Strict vegetarian diet, defined as lack of milk, eggs, and diary products HEALTHY CONTROL SUBJECT INCLUSION/EXCLUSION: -In addition to the criteria specified above, healthy controls must be in good physical health and not on chronic medications.