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

NCT00001723 | Completed Phase 2 Results DMC

• 2 other identifiers: 98011198-CH-0111
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

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).

Conditions

Diabetes Mellitus; Hypertension; Metabolic Disease; Obesity; Sleep Apnea Syndrome

Keywords

Dyslipidemia; Race; Body Fat; Visceral Fat; Sleep Apnea; Fat-Soluble Vitamins; Type 2 Diabetes; Obesity; Childhood Obesity

Outcome Measures

Primary Outcomes (1)

• Change in BMI Standard Deviation Score

  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.

  baseline to 6 months

Secondary Outcomes (4)

• Change in Body Weight

  baseline to 6 months

• Change in Body Mass Index

  baseline to 6 months

• Change in Body Fat (kg)

  baseline to 6 months

• Effect of Race on Change in Weight (kg)

  baseline to 6 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Matching placebo 120 mg TID x 6 months plus a behavioral weight loss program

Drug: Placebo

Orlistat

EXPERIMENTAL

Orlistat 120 mg TID for 6 months plus a behavioral weight loss program

Drug: Orlistat

Interventions

Orlistat DRUG

Subjects receive drug for 6 months plus a 12 week intensive behavioral weight los program. Subjects return for monthly visits for 3 more months.

Also known as: Xenical (orlistat)capsules

Orlistat

Placebo DRUG

Subjects receive drug for 6 months plus a 12 week intensive behavioral weight los program. Subjects return for monthly visits for 3 more months.

Also known as: Placebo capsule

Placebo

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Good general health.
• Age 12-17 years at study entry.
• Body mass index (BMI) for age above the 5th percentile and below 85th percentile, which is considered normal weight by CDC growth chart standards.
• For females with childbearing potential, a negative pregnancy test at initial evaluation.
• Race of all four grandparents self-identified as either all Caucasian or all African American.
• Volunteers will be excluded for the following reasons:
• Presence of past or present medical problems which would impair performance during the exercise tests;

Sponsors & Collaborators

• Jack Yanovski: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• Roche Pharma AG: collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (11)

• Kuczmarski RJ, Flegal KM, Campbell SM, Johnson CL. Increasing prevalence of overweight among US adults. The National Health and Nutrition Examination Surveys, 1960 to 1991. JAMA. 1994 Jul 20;272(3):205-11. doi: 10.1001/jama.272.3.205.

  PMID: 8022039 BACKGROUND

• Drent ML, Larsson I, William-Olsson T, Quaade F, Czubayko F, von Bergmann K, Strobel W, Sjostrom L, van der Veen EA. Orlistat (Ro 18-0647), a lipase inhibitor, in the treatment of human obesity: a multiple dose study. Int J Obes Relat Metab Disord. 1995 Apr;19(4):221-6.

  PMID: 7627244 BACKGROUND

• Must A, Jacques PF, Dallal GE, Bajema CJ, Dietz WH. Long-term morbidity and mortality of overweight adolescents. A follow-up of the Harvard Growth Study of 1922 to 1935. N Engl J Med. 1992 Nov 5;327(19):1350-5. doi: 10.1056/NEJM199211053271904.

  PMID: 1406836 BACKGROUND

• Chanoine JP, Hampl S, Jensen C, Boldrin M, Hauptman J. Effect of orlistat on weight and body composition in obese adolescents: a randomized controlled trial. JAMA. 2005 Jun 15;293(23):2873-83. doi: 10.1001/jama.293.23.2873.

  PMID: 15956632 BACKGROUND

• McDuffie JR, Calis KA, Uwaifo GI, Sebring NG, Fallon EM, Frazer TE, Van Hubbard S, Yanovski JA. Efficacy of orlistat as an adjunct to behavioral treatment in overweight African American and Caucasian adolescents with obesity-related co-morbid conditions. J Pediatr Endocrinol Metab. 2004 Mar;17(3):307-19. doi: 10.1515/jpem.2004.17.3.307.

  PMID: 15112907 RESULT

• McDuffie JR, Calis KA, Booth SL, Uwaifo GI, Yanovski JA. Effects of orlistat on fat-soluble vitamins in obese adolescents. Pharmacotherapy. 2002 Jul;22(7):814-22. doi: 10.1592/phco.22.11.814.33627.

  PMID: 12126214 RESULT

• McDuffie JR, Calis KA, Uwaifo GI, Sebring NG, Fallon EM, Hubbard VS, Yanovski JA. Three-month tolerability of orlistat in adolescents with obesity-related comorbid conditions. Obes Res. 2002 Jul;10(7):642-50. doi: 10.1038/oby.2002.87.

  PMID: 12105286 RESULT

• Omotosho YB, Reynolds JC, Yanovski JA, Tatsi C. Body Composition and Fat Deposition in Children with Cushing Disease and Associations with Cardiometabolic Risk Factors. J Pediatr. 2025 Dec 3;290:114933. doi: 10.1016/j.jpeds.2025.114933. Online ahead of print.

  PMID: 41349930 DERIVED

• Schvey NA, Shank LM, Tanofsky-Kraff M, Ramirez S, Altman DR, Swanson T, Rubin AG, Kelly NR, LeMay-Russell S, Byrne ME, Parker MN, Broadney MM, Brady SM, Yanovski SZ, Yanovski JA. Weight-based teasing in youth: Associations with metabolic and inflammatory markers. Pediatr Obes. 2021 Mar;16(3):e12729. doi: 10.1111/ijpo.12729. Epub 2020 Oct 15.

  PMID: 33059389 DERIVED

• Han JC, Reyes-Capo DP, Liu CY, Reynolds JC, Turkbey E, Turkbey IB, Bryant J, Marshall JD, Naggert JK, Gahl WA, Yanovski JA, Gunay-Aygun M. Comprehensive Endocrine-Metabolic Evaluation of Patients With Alstrom Syndrome Compared With BMI-Matched Controls. J Clin Endocrinol Metab. 2018 Jul 1;103(7):2707-2719. doi: 10.1210/jc.2018-00496.

  PMID: 29718281 DERIVED

• Radin RM, Tanofsky-Kraff M, Shomaker LB, Kelly NR, Pickworth CK, Shank LM, Altschul AM, Brady SM, Demidowich AP, Yanovski SZ, Hubbard VS, Yanovski JA. Metabolic characteristics of youth with loss of control eating. Eat Behav. 2015 Dec;19:86-9. doi: 10.1016/j.eatbeh.2015.07.002. Epub 2015 Jul 18.

  PMID: 26210388 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Diabetes Mellitus; Hypertension; Metabolic Diseases; Obesity; Sleep Apnea Syndromes; Dyslipidemias; Diabetes Mellitus, Type 2; Pediatric Obesity

Interventions

Orlistat

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Nutritional and Metabolic Diseases; Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Lipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals

Results Point of Contact

• Title: Jack A. Yanovski, MD, PhD, Chief SGO, PDEGEN
• Organization: National Institute of Child Health and Human Development, NIH

yanovskj@mail.nih.gov

301-496-4686

Study Officials

• Jack A Yanovski, M.D.

  Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Section Chief, Section on Growth and Obesity, PDEGEN, NICHD

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: May 1, 1998
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: December 18, 2012
• Results First Posted: December 18, 2012

Record last verified: 2012-11

Locations

US (1)