Safety and Efficacy of Xenical in Children and Adolescents With Obesity-Related Diseases

Phase 2

Completed

Conditions: Diabetes Mellitus
Hypertension
Metabolic Disease
Obesity
Sleep Apnea Syndrome

Interventions: Drug: Placebo
Drug: Orlistat

Registration Number: NCT00001723

Lead Sponsor: Jack Yanovski

Brief 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).

Detailed Description: Obesity is a condition affecting one-third of the adult U.S. population and is a major risk factor for the development of Type 2 diabetes, hyperlipidemia, hypertension, and other cardiovascular and respiratory disorders. Individuals with the onset of obesity during childhood or adolescence are at increased risk for obesity-related, comorbid conditions, both during adolescence and later in life. African American girls and women are at particular risk for obesity, and have substantial rates of obesity-related morbidity and mortality. Further, African American adult women have a less satisfactory response to many therapeutic approaches used to treat obesity. At present, there are no medical therapies proven effective for the amelioration of severe obesity in children or adolescents. One medication that may have a favorable risk-benefit ratio in pediatric populations is orlistat (Xenical(Trademark), Hoffmann LaRoche). Orlistat acts by inhibiting gastrointestinal lipases, interfering with the absorption of approximately 1/3 of ingested dietary fat. Orlistat appears to be effective for reducing weight and obesity-associated comorbidities in obese adults. We propose to determine the safety, tolerability, and efficacy of orlistat in 12-17 year-old severely obese African American and Caucasian children and adolescents who have one or more obesity-related comorbidity (hypertension, hyperlipidemia, sleep apnea, hepatic steatosis, insulin-resistance, impaired glucose tolerance, or Type 2 diabetes). Under this protocol, we have conducted an open-label pilot study of orlistat in twenty subjects, suggesting orlistat has a similar side effect profile in adolescents as in adults. We wish to determine the safety and efficacy of orlistat in reducing obesity-related comorbidities using a randomized, double-blind, placebo-controlled clinical trial. All study participants will be enrolled in a psycho-educational weight loss program that includes nutrition education, cognitive-behavioral self-monitoring strategies, and promotion of physical activity. We will also study the effects of orlistat on fat preferences, and study the influence of genetic variables on energy expenditure and weight loss during treatment. A group of healthy, non-overweight children and adolescents will complete questionnaires and exercise studies as a control group for interpretation of results in overweight children and adolescents, but will not undergo phlebotomy or receive any medication.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 200

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Matching placebo 120 mg TID x 6 months plus a behavioral weight loss program
Orlistat	Orlistat	Orlistat 120 mg TID for 6 months plus a behavioral weight loss program

Primary Outcome Measures

Name	Time	Method
Change in BMI Standard Deviation Score	baseline to 6 months	Body Mass index standard deviation score calculated for age and sex according to Centers for Disease Control standards. See: Kuczmarski RJ, Ogden CL, Guo SS, Grummer-Strawn LM, Flegal KM, Mei Z et al. 2000 CDC Growth Charts for the United States: methods and development. Vital Health Stat 11 2002; (246): 1-190.

Secondary Outcome Measures

Name	Time	Method
Change in Body Weight	baseline to 6 months	Weight in kg
Change in Body Mass Index	baseline to 6 months	BMI is calculated in kg/m2. Change from baseline to 6 months of treatment
Change in Body Fat (kg)	baseline to 6 months	body fat distribution measures obtained from Dual-energy X-ray Absorptiometry (DEXA)
Effect of Race on Change in Weight (kg)	baseline to 6 months	Difference in change of weight in kg according to race (Non-Hispanic White versus Non-Hispanic Black)