Safety and Efficacy of Xenical in Children and Adolescents With Obesity-Related Diseases
Condition: Diabetes Mellitus; Hypertension; Metabolic Disease; Obesity; Sleep Apnea Syndrome
MeSH terms: Sleep Apnea Syndromes; Obesity; Metabolic Diseases
Intervention: Orlistat; Placebo
Intervention description: Subjects receive drug for 6 months plus a 12 week intensive behavioral weight los program. Subjects return for monthly visits for 3 more months.; Subjects receive drug for 6 months plus a 12 week intensive behavioral weight los program. Subjects return for monthly visits for 3 more months.
Intervention MeSH terms: Orlistat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 200.0
Sex: All
Minimum age: 12 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Dyslipidemia; Race; Body Fat; Visceral Fat; Sleep Apnea; Fat-Soluble Vitamins; Type 2 Diabetes; Obesity; Childhood Obesity

Summary:

      Obesity is a condition affecting one-third off the U.S. population and is a major risk actor
      for the development of Type 2 diabetes, hyperlipidemia (increased levels of fat in the
      blood), hypertension (high blood pressure), and other disorders of the heart and lungs.
      Individuals with the onset of obesity during childhood or adolescence are at an increased
      risk of obesity-related, diseases, both during adolescence and later in adult life.

      African American girls and women are at an increased risk for obesity, and have substantial
      rates of obesity-related diseases and causes of death. Further, many African American adult
      women fail to respond to many of the therapeutic approaches used to treat obesity. At present
      there are no medical therapies proven effective for the correction of severe obesity in
      children or adolescents.

      One medication that may have a favorable risk-benefit ratio in pediatric populations is
      Orlistat (Xenical, Hoffmann LaRoche). Orlistat works by preventing the action of enzymes in
      the digestive process, interfering with the absorption of approximately 1/3 of the fat eaten
      in the diet. Xenical appears to be effective for reducing weight and obesity-associated
      diseases in obese adults.

      Researchers propose to determine the safety, tolerability, and efficacy of Xenical in 12-17
      year old severely obese African American and Caucasian children and adolescents who have one
      or more obesity-related disease (hypertension, hyperlipidemia, sleep apnea, hepatic
      steatosis, insulin resistance, impaired glucose tolerance, or Type 2 diabetes).
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Good general health. Individuals taking medications for obesity-related comorbid conditions
        will not be excluded.

        Obesity: body mass index for age and triceps skinfold above the 95th percentile (determined
        by NHANES I age-, sex-, and race- specific data). All subjects will be required to be over
        60 kg in body weight.

        Evidence for a quantifiable obesity-related comorbidity. Examples include: systolic or
        diastolic hypertension (determined by age-specific charts); frank Type 2 diabetes, impaired
        glucose tolerance assessed by oral glucose tolerance testing; hyperinsulinemia (defined as
        a fasting insulin greater than 15 mIU/mL); significant hyperlipidemia (total cholesterol
        greater than 200 mg/dL, LDL cholesterol greater than 129 mg/dL or fasting triglycerides
        greater than 200 mg/dL); hepatic steatosis (SGPT or SGOT above normal range with negative
        hepatitis studies) or sleep apnea documented by a sleep study.

        Age 12 to 17 years at the start of the study.

        For girls with childbearing potential, a negative pregnancy test before taking and while
        taking study medication. Sexually active females must be using an effective form of birth
        control. These methods include total abstinence (no sex), oral contraceptives ("the pill"),
        an intrauterine device (IUD), levonogestrol implants (Norplant), or medroxyprogesterone
        acetate injections (Depo-provera shots). If one of these cannot be used, contraceptive foam
        with a condom is recommended.

        Race of all four grandparents self-identified as either all Caucasian or all African
        American.

        EXCLUSION CRITERIA:

        Volunteers will be excluded (and referred to non-experimental treatment programs) for the
        following reasons:

        Presence of renal, hepatic (other than obesity-related steatosis), gastrointestinal, most
        endocrinologic (e.g., Cushing syndrome), or pulmonary disorders (other than either asthma
        not requiring continuous medication or sleep apnea-related disorders);

        Adolescent girls who are pregnant, who are currently nursing an infant, or who are having
        unprotected intercourse;

        Individuals who have, or whose parent or guardians have, current substance abuse or a
        psychiatric disorder or other condition which, in the opinion of the investigators, would
        impede competence or compliance or possibly hinder completion of the study;

        Subjects who regularly use prescription medications unrelated to the complications of
        obesity. Oral contraceptive use will be permitted, provided the contraceptive has been used
        for at least two months before starting study medication. The use of over-the-counter and
        prescription medications will be reviewed on a case-by-case basis; depending on the
        medication, subjects who have continued to take prescription medication for at least 3
        months prior to study entry may be eligible;

        Recent use (within six months) of anorexiant medications for the purpose of weight
        reduction;

        Inability to undergo MRI (e.g., volunteers with metal within their bodies including cardiac
        pacemakers, neural pacemakers, aneurysmal clips, shrapnel, ocular foreign bodies, cochlear
        implants, non-detachable electronic or electromechanical devices such as infusion pumps,
        nerve stimulators, bone growth stimulators, etc. that are contraindications).

        For pilot study participants, hypersensitivity or allergy to methylene blue. Individuals
        with documented G6PD deficiency will be excluded.

        INCLUSION CRITERIA: HEALTHY CONTROL CHILDREN AND ADOLESCENTS:

        Volunteers will qualify for inclusion if they meet the following criteria:

          1. Good general health.

          2. Age 12-17 years at study entry.

          3. Body mass index (BMI) for age above the 5th percentile and below 85th percentile,
             which is considered normal weight by CDC growth chart standards.

          4. For females with childbearing potential, a negative pregnancy test at initial
             evaluation.

          5. Race of all four grandparents self-identified as either all Caucasian or all African
             American.

        EXCLUSION CRITERIA: HEALTHY CONTROL CHILDREN AND ADOLESCENTS:

        Volunteers will be excluded for the following reasons:

          1. Presence of past or present medical problems which would impair performance during the
             exercise tests;

          2. Females who are pregnant, or who are currently nursing an infant;

          3. Individuals who have, or whose parent or guardian has, current substance abuse or a
             psychiatric disorder or other condition that in the opinion of the investigators would
             impede competence or possibly hinder completion of the study;

          4. Recent weight change of more than 3% of body weight in the past two months;

          5. Recent use (within six months) of anorexiant medications for the purpose of weight
             reduction;

          6. Physical impairments that would prevent completion of either the walk/run test or the
             cycle test.