Please select the eligibility criteria that correspond to the clinical trial below.
Title: A 12 Month Study to Assess Safety and Efficacy of Meridia (Sibutramine Hydrochloride Monohydrate) 10 and 15 mg in Obese Adolescents
Brief Summary: The purpose of this study is to assess the effectiveness of sibutramine on weight loss, reduction in body size and improvement in metabolic risk factors and safety in obese adolescents.


Options:
A: Inclusion Criteria:

* Age 8-19 years old
* Subject able to give assent, and parent/guardian capable of giving consent on behalf of the child
* Body mass index (BMI) ≥ 99th percentile (based on gender and age)

Exclusion Criteria:

* Type 1 or 2 diabetes mellitus
* Initiation of a new drug therapy within the past 30 days prior to the screening visit
* BMI ≥ 55
* History of weight loss surgery
* Obesity from a genetic cause (e.g., Prader-Willi)
* Central nervous system injury or severe neurological impairment
* Known systolic or diastolic dysfunction or heart failure
* Females who are currently pregnant or planning to become pregnant
* Liver enzymes \> 2.5 times upper limit of normal
* Severe renal impairment (defined as creatinine clearance \<30 mL/min)
* Gastrointestinal disease
B: Inclusion Criteria:

* Obese adolescent males and females in good general health with a lower limit of inclusion by BMI 2 units above the U.S. weighted mean for the 95th percentile for weight based on age and gender to a BMI of 44 kg/m2, ages 12 to 16 years at randomization. (Efforts should be directed to obtain a study population comprising 50% to 75% females and at least 30% African- Americans across the study. Each site should enroll similar numbers of patients at each age within the 12 to 16 year old age range.)
* Both the patient and legal guardian/parent must be able to communicate meaningfully with the investigator, be legally competent, and provide written informed consent/assent.
* All patients must exhibit sufficient comprehension of written materials to be able to follow diet and exercise recommendations, and to complete written behavioral assessments.
* For females of childbearing potential, a negative pregnancy test will be required prior to study inclusion. Female patients, if sexually active, must be using adequate contraceptive precautions (i.e., oral contraceptives, approved hormonal implant, intrauterine device, diaphragm with spermicide, condom with spermicide). Oral contraceptive use is permitted if used for at least 3 months before starting study medication.
* A serum pregnancy test, which must be negative, is required of all females.
* The patient must have at the screening and baseline visits a mean systolic blood pressure \<=130 mm Hg, a diastolic blood pressure \<=85 mm Hg, and a pulse rate \<=95 beats per minute. Treated hypertensives are allowed in the study if medication has been stable for at least 3 months.

Exclusion Criteria:

* The patient must not have a history of anorexia nervosa.
* The patient must not have a history of clinically significant cardiac disease, congenital heart disease, any clinically significant abnormal cardiac condition, or be known to have a clinically significantly abnormal ECG. Specifically excluded conditions include coronary artery disease, clinically significant cardiac arrhythmias, and congestive heart failure.
* The patient must not have a history of stroke.
* The patient must not have a history of asthma requiring chronic oral corticosteroid therapy. A short course (\<7 days) of oral corticosteroid medication is permitted for an acute exacerbation.
* The patient must not have a history of narrow angle glaucoma.
* The patient must not have a history of gallstones unless status post cholecystectomy.
* The patient must not have a history of seizures with the exception of childhood febrile seizure.
* The patient must not have evidence of possible renal dysfunction (creatinine \>1.7 mg/dL) or hepatic dysfunction (ALT \>50 IU/L, bilirubin \>1.0 mg/dL). Patients must not have evidence of active or chronic Hepatitis B or C infection.
* The patient must not be using any of the following medications at any time during the study: monoamine oxidase inhibitors (e.g., furazolidone, phenelzine, procarbazine hydrochloride, selegiline), antidepressant agents (including the use of antidepressant agents for more than 2 weeks during the 90 day period prior to screening), lithium, serotonin reuptake inhibitors, certain opioids (dextromethorphan, meperidine, pentazocine, and fentanyl), prescribed or over-the-counter weight loss agents, centrally acting appetite suppressants, tryptophan, sympathomimetics, serotonergic anti-migraine agents (including sumatriptan succinate, dihydroergotamine, etc.) or any other medication that, in the opinion of the Investigator, may pose harm to the patient, obscure the effects of study medication or interfere with the process of drug absorption, distribution, metabolism, or excretion (i.e., enzyme inducers or enzyme inhibitors).
* Patients may not be taken off an antidepressant for the purposes of entering this study.
* The patient and parent/legal guardian must not have a history of alcohol or drug addiction or substance abuse within the previous two years.
* Patients must not be above the 95th percentile for gender and age for the following categories at Screening, as assessed by the Child Behavior CheckList: "thought problems", "delinquent behavior", "aggressive behavior", or "attention problems".
* The patient must not have a t-score of greater than 65 (significantly above average) for the total Child Depression Inventory score.
* The patient must not have participated in rigorous, structured weight loss programs for more than 2 weeks within the past 6 months prior to screening. Continuing participation in less rigorous programs such as Weight Watchers is allowed; however, the patients must have been a participant for at least 6 months prior to screening to be allowed in the study.
* The patient must not have participated in any investigational drug study within thirty (30) days prior to screening.
* The patient must not have used prescription or OTC (or herbal) weight control medication for more than two (2) weeks during the 180 day period immediately preceding screening. In addition, any such medication is not allowed in the trial.
* The patient must not have previously been a patient/subject in a sibutramine trial or have otherwise used sibutramine.
* Pregnancy
* Pathophysiologic or genetic syndromes associated with obesity (Cushing's syndrome, Turner's syndrome, Prader-Willi syndrome; etc.)
* Diabetes mellitus (FBG greater than or equal to 126 mg/dL)
* Untreated hypothyroidism (TSH greater than 4.0 mU/L for a second generation test)
* Malignancy
* Patient must not have drug screen positive for recreational drugs.
* Coagulopathies or bleeding disorders
* Gastric bypass or other surgical procedure which has the potential to interfere with absorption of study medication, or gastric restrictive surgery.
* Major psychiatric illness in either the patient or patient's legal guardian/parent(s) such as bi-polar disorder, ADD, major depression, bulimia, schizophrenia, psychosis; etc.
* Failure to maintain a minimum level of academic achievement during the previous 6 months prior to screening (patients are excluded if receiving multiple failing grades in school).
* Any other severe medical or psychiatric disorder that precludes participation.
C: 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).
D: Inclusion Criteria:

* Obese adolescents defined as BMI greater than the 95th percentile for age and gender
* Metformin naive subjects

Exclusion Criteria:

* Elevated fasting plasma glucose ≥ 6.0 mmol/L
* 2 hour plasma glucose ≥ 11.1 mmol/L after a standard glucose load
* A1C \> 6.0%
* Medication other than "over the counter" drugs, oral contraceptive pill or thyroid hormone replacement
* Smoking
* Pregnancy
* Renal insufficiency (serum creatinine \> the upper limit of normal)
* Hepatic dysfunction (\> 1.5 times the upper limit of normal for AST and ALT)
* Latex Allergy
* Hypersensitivity to metformin or its ingredients
* Breast feeding
* Subjects with a history of lactic acidosis
* Abnormal creatinine clearance
* HIV, HBV, and HCV infections
* Drug and alcohol abuse
* Severe mental disorders
* Subjects who are planning radiologic exams involving in i.v. injection of iodinated contract materials
* Participation in another clinical trial
* Significant history or presence of cardiovascular, pulmonary, gastrointestinal, immunologic, endocrine, neurologic disorders
* Malignant diseases
* Previous exposure to any pharmaceutical antidiabetic agent

Answer: B