Safety and Efficacy of Xenical in Children and Adolescents with Obesity-Related Diseases
This study is currently recruiting patients.
Purpose
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).
Condition
|
Treatment or Intervention |
Phase |
Diabetes Mellitus Hypertension Metabolic Disease Obesity Sleep Apnea Syndrome
|
Drug: Orlistat
|
Phase II
|
MedlinePlus related topics: Diabetes; High Blood Pressure; Metabolic Disorders; Obesity; Sleep Apnea
Study Type: Interventional
Study Design: Treatment, Safety/Efficacy
Official Title: Safety and Efficacy of Orlistat (Xenical, Hoffmann LaRoche) in African American and Caucasian Children and Adolescents with
Obesity-Related Comorbid Conditions
Further Study Details:
Expected Total Enrollment:
370
Study start: May 14, 1998
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.
Eligibility
Genders Eligible for Study:
Both
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.
Location
and Contact
Information
Maryland National Institute of Child Health and Human Development (NICHD), 9000 Rockville Pike,
Bethesda,
Maryland,
20892,
United States; Recruiting
Patient Recruitment and Public Liaison Office
1-800-411-1222
prpl@mail.cc.nih.gov
TTY
1-866-411-1010
More Information
Detailed Web Page
Publications
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.
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.
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.
Study ID Numbers:
980111; 98-CH-0111
Record last reviewed:
April 30, 2004
Last Updated:
April 30, 2004
Record first received:
November 3, 1999
ClinicalTrials.gov Identifier:
NCT00001723Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-29