Please select the eligibility criteria that correspond to the clinical trial below.
Title: Safety and Efficacy of Orlistat (Xenical, Hoffmann LaRoche) in African American and Caucasian Children and Adolescents With Obesity-Related Comorbid Conditions
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).


Options:
A: Inclusion Criteria (during Screening and Run-in period):

* Diabetes by ADA criteria (laboratory determinations of fasting glucose ≥ 126 mg/dL, random glucose ≥ 200 mg/dL, or two-hour OGTT glucose ≥ 200 mg/dL) documented and confirmed in medical record. For patients diagnosed with diabetes during screening who have a normal fasting glucose but an elevated two-hour glucose during an OGTT, the HbA1c must be ≥ 6%.
* Duration since diagnosis less than two years by date of randomization.
* BMI ≥ 85th percentile documented at time of diagnosis or at screening.
* Fasting C-peptide at screening (drawn at least one week after treatment for ketosis or acidosis, if applicable) \> 0.6 ng/mL.
* Absence of pancreatic autoimmunity (both GAD and ICA512 negative).
* Age 10-17, with randomization prior to 18th birthday.
* Signed informed consent/assent forms for the pre-randomization period.
* A family member or adult closely involved in the daily activities of the child agrees to participate in the child's treatment.
* Fluency in English or Spanish for both child and family member.
* Patient and family able to fully participate in trial protocol in the opinion of the investigator.

Exclusion Criteria (during Screening and Run-in period):

* Participating in another interventional research study protocol in the past 30 days.
* Genetic syndrome or disorder known to affect glucose tolerance other than diabetes.
* Patient on inhaled steroids at dose above 1000 mcg daily Flovent equivalent.
* Patient on a course of oral steroids within the last 60 days or on oral steroids more than 20 days during the past year.
* Patient on medication(s) that are known to affect insulin sensitivity or secretion within the last 30 days.
* Patient on medication(s) that are known to cause weight gain within the last 30 days.
* Patient on any weight-loss medication(s) within the last 30 days.
* Patient on medication(s) known to affect the metabolism of study drug.
* Inability to comprehend the lowest grade level at which lifestyle intervention materials are prepared, for both child and participating family member.
* Females who are pregnant, planning to become pregnant within two years of enrollment, or who admit sexual activity without appropriate contraception.
* Calculated creatinine clearance \< 70 mL/min.
* Any transaminase \> 2.5 ULN. If any transaminase 1.5-2.5 times ULN, then patient must be appropriately evaluated by PCP (minimum evaluation includes ceruloplasmin level, alpha-1 antitrypsin phenotype, ANA, anti-smooth muscle antibody, anti-LKM antibody, anti-HCV, and anti-HBc total antibody not IgM, iron, and TIBC) and is eligible if all other causes for elevation are ruled out and it is presumed due only to non-alcoholic fatty liver disease (NAFLD).
* Diabetic ketoacidosis (DKA) at any time after diagnosis unless only a single episode of DKA related to a significant medical illness.
* Physical limitations preventing patient from being randomized to the lifestyle intervention.
* Patient plans to leave the geographic area within one calendar year.
* Abnormal reticulocyte count or HbA1c chromatogram at time of screening.
* Admitted use of anabolic steroids within the past 60 days.
* Other significant organ system illness or condition (including psychiatric or developmental disorder) that would prevent participation in the opinion of the investigator.
* Patient participates in a formal weight-loss program.

Inclusion Criteria (post Run-in and Randomization):

* Duration since diagnosis less than 2 years at randomization.
* HbA1c \< 8% on metformin alone.
* Age 10-17, with randomization before patient is 18 years old.
* Signed consent/assent forms for randomization and the post-randomization phase.
* A family member or adult closely involved in the daily activities of the child agrees to participate in the child's treatment.
* Fluency in English or Spanish for both child and family member.
* Patient and family able to fully participate in trial protocol in the opinion of the investigator.

Exclusion Criteria (post Run-in and Randomization):

* Refractory hypertension: average systolic blood pressure ≥ 150 mmHg or average diastolic blood pressure ≥ 95 mmHg despite appropriate medical therapy.
* Refractory hyperlipidemia: total cholesterol \> 300 mg/dL or LDL \> 190 mg/dL or triglycerides \> 800 mg/dL, despite appropriate medical therapy.
* Refractory anemia: hematocrit \< 30% or hemoglobin \< 10 gm/dL despite appropriate medical therapy.
* Patient on a thiazolidinedione (TZD) within the last 12 weeks.
* Patient on non-study diabetes medications within the past 6 weeks.
* Patient on inhaled steroids at dose above 1000 mcg daily Flovent equivalent.
* Patient on a course of oral steroids within the last 60 days or on oral steroids more than 20 days during the past year.
* Patient on medication(s) that are known to affect insulin sensitivity or secretion within the last 30 days.
* Patient on medication(s) that are known to cause weight gain within the last 30 days.
* Patient on any weight-loss medication(s) within the last 30 days.
* Patient on medication(s) known to affect the metabolism of study drug.
* Inability to comprehend the lowest grade level at which lifestyle intervention materials are prepared, for both child and participating family member, assessed by mastery of standard diabetes education program administered during run-in.
* Inability to comply with requirements of study during run-in period.
* Females who are pregnant, planning to become pregnant within two years of enrollment, or who admit sexual activity without appropriate contraception.
* Calculated creatinine clearance \< 70 mL/min.
* Physical limitations preventing patient from being randomized to the lifestyle intervention.
* Patient plans to leave the geographic area within one calendar year.
* Admitted use of anabolic steroids within 60 days.
* Other significant organ system illness or condition (including psychiatric or developmental disorder) that would prevent participation in the opinion of the investigator.
* Patient participates in a formal weight loss program.
* Episode of DKA during the run-in.30.
* Edema at the time of randomization (a participant who experiences edema during run-in must have recovered within 2 weeks and be edema free for 1 week prior to randomization).
B: * INCLUSION CRITERIA:
* Age 12-17 years
* Female
* BMI greater than or equal to 85th percentile for age.
* CES-D greater than or equal to 16
* Good general health
* T2D or prediabetes (impaired fasting glucose greater than or equal to 100 mg/dL or impaired glucose tolerance: 2h glucose tolerance test glucose greater than or equal to 140 mg/dL) family history in a first- or second- degree relative.
* English-speaking

EXCLUSION CRITERIA:

* Current major depressive episode
* Current psychiatric symptoms requiring treatment
* Fasting glucose \>126 mg/dL
* 2-hour OGTT glucose \>200 mg/dL
* Pregnancy
* Use of medication affecting IR, weight, or mood
* Current psychotherapy or weight loss treatment
C: * INCLUSION CRITERIA:

Good general health.

Age 2 to 18 years.

EXCLUSION CRITERIA:

Volunteers will be excluded for the following reasons:

Presence of renal, hepatic, gastrointestinal, most endocrinologic (e.g., Cushing's syndrome) or pulmonary disorders (other than asthma not requiring continuous medication);

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 the ability to give informed consent or possibly hinder completion of the study;

Subjects who regularly use prescription medications are not eligible. The use of over-the-counter medications will be reviewed on a case-by-case basis;

For those sub-studies involving MRI, 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).
D: * 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.

Answer: D