Body Weight Regulation in Patients With Narcolepsy
Condition: Narcolepsy
MeSH terms: Narcolepsy; Body Weight
Study type: Observational

Summary: 
      This study will measure energy expenditure (the rate at which the body burns calories),
      physical activity and caloric intake in people with narcolepsy to learn more about how the
      risk of becoming overweight or diabetic may be affected.

      Healthy control subjects and people with narcolepsy between 18 and 55 years of age may be
      eligible for this study. Participants are withdrawn from their narcolepsy medication and
      undergo the following tests and procedures over 5 weeks before resuming medications.

        -  Blood draw for genetic studies.

        -  Collection of a cerebrospinal fluid sample.

        -  Diet to keep subjects' weight constant.

        -  Activity watch, using a device worn on the wrist to measure amount of movement, and an
           activity monitor worn at the waist to measure physical activity and caloric expenditure.

        -  Questionnaires about sleepiness, symptoms, food intake, exercise and mood.

        -  24-hour urine collection and 24-hour blood draw to measure hormones.

        -  Glucose tolerance test. The subject drinks a sugar solution and blood samples are
           collected through a catheter before drinking the solution and 30 minutes, 1, 2 and 3
           hours after drinking it.

        -  Startle reflex test. Subjects hear a loud noise through headphones and are asked to look
           at pictures.

        -  Sleep study to evaluate sleep-related breathing disturbances and record information
           about sleep stages.

        -  Indirect calorimetry test to measure how fast the body uses calories. A plastic canopy
           is placed over the face for several minutes to capture the air exhaled to analyze oxygen
           use. To measure the energy associated with meals, the same measurements are taken after
           the subject eats lunch.

        -  CT scan of the abdomen to see how much fat is deposited in the abdomen, and DEXA scan of
           the whole body to see the percentage of fat and muscle.

        -  Plethysmography. Participants sit in an enclosed chamber while the mass and volume of
           the body are measured by changes in air pressure.

        -  Neuropsychological testing to assess thought processes.

        -  Continuous 24-hour heart rate measurement.

        -  Metabolic chamber. Subjects spend 24 hours in a small room to measure the amount of
           oxygen inhaled and carbon dioxide exhaled.

        -  Walking/running test to assess level of physical conditioning.

        -  Dexamethasone CRH (corticotropin-releasing hormone) suppression test and CRH stimulation
           test. Subjects receive eight doses of 0.5 mg dexamethasone every 6 hours for a day and a
           half. After the last dose, two blood samples are drawn, then a dose of CRH is injected,
           and then six more blood samples are drawn over the next 3 hours.

        -  TRH (thyrotropin-releasing hormone) stimulation test. Subjects are given TRH through a
           vein, and several blood samples are then drawn over the next 3 hours.

        -  Doubly labeled water test. Subjects drink a dose of "heavy" water. Urine samples are
           collected at 2, 3 and 5 hours after drinking and again for two 4-hour collections a week
           later.
    

Detailed description: 
      BACKGROUND: Several cross-sectional studies have suggested that subjects with narcolepsy have
      increased body mass index (BMI) and insulin resistance. These subjects exhibit a decrease in
      cerebrospinal fluid (CSF) orexin levels, which has been causally linked to the clinical
      manifestations of this disease. Orexins are peptides expressed in a brain region, the lateral
      hypothalamic area, which stimulate appetite and modulate sleep. Low CSF orexin levels provoke
      narcolepsy-like behavior, such as excessive daytime sleepiness and a sudden loss of muscle
      tone known as cataplexy.

      OBJECTIVES: The primary objective of this study is to determine whether subjects with
      narcolepsy have lower energy expenditure compared to healthy matched controls. In addition,
      we will assess food intake, physical activity, and other relevant parameters.

      STUDY POPULATION: 18 to 55 year old men and premenopausal women with narcolepsy and healthy
      matched controls

      DESIGN: This is a cross-sectional, case-controlled study of subjects with narcolepsy matched
      on a one-to-one basis with healthy, non-narcoleptic control subjects.

      OUTCOME PARAMETERS: We will assess metabolic, hormonal, and energy expenditure parameters in
      subjects with narcolepsy. Outcomes: energy expenditure by various methods (indirect
      calorimetry, metabolic chamber, doubly-labeled water method); leptin circadian levels
      (frequent 24h sampling); physical activity, characterization of the main endocrine axes, and
      other relevant parameters.
    

Keywords: Obesity; Leptin; Sleep Attacks; Energy Metabolism; Healthy Control; Narcolepsy; Healthy Volunteer; HV