Safety and Efficacy of Xenical in Children and Adolescents With Obesity-Related Diseases
Information source: National Institutes of Health Clinical Center (CC)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Diabetes Mellitus; Hypertension; Metabolic Disease; Obesity; Sleep Apnea Syndrome
Intervention: Orlistat (Drug)
Phase: Phase 2
Status: Active, not recruiting
Sponsored by: National Institute of Child Health and Human Development (NICHD)
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).
Official title: Safety and Efficacy of Orlistat (Xenical, Hoffmann LaRoche) in African American and Caucasian Children and Adolescents With Obesity-Related Comorbid Conditions
Study design: Treatment, Randomized, Double-Blind, Parallel Assignment, Safety/Efficacy Study
Primary outcome: Changes in body weight and adipose tissue as determined by FMI-standard deviation score (BMI-SDS), air displacement plethysmography, and DXA scan.
Secondary outcome: Changes in skinfold thickness, body circumferences, BIA, and MRI, the insulin and glucose values from the clamp study, changes in blood pressure, total cholesteraol, triglycerides, HDL cholesteraol, LDL, small dense LDL, leptin, and IGFBP1.
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.
Minimum age: 12 Years.
Maximum age: 17 Years.
- 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
Volunteers will be excluded (and referred to non-experimental treatment programs) for the
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
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
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
5. Race of all four grandparents self-identified as either all Caucasian or all African
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
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
6. Physical impairments that would prevent completion of either the walk/run test or the
Locations and Contacts
National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland 20892, United States
NIH Clinical Center Detailed Web Page
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.
Starting date: May 1998
Last updated: March 15, 2008