Please select the eligibility criteria that correspond to the clinical trial below.
Title: GLP-1 Therapy for Weight Loss and Improved Glucose Tolerance in Obese Children: A Randomized, Controlled, Pilot Study
Brief Summary: The prevalence of severely obese children is on the rise. Behavioral therapies for weight loss are successful in some, but others need more aggressive approaches such as drug therapy. In addition, up to 25% of severely obese children have impaired glucose tolerance (IGT), which places them at significantly elevated risk of developing type 2 diabetes mellitus and cardiovascular disease. Although various drug therapies for weight loss and IGT have been explored in adults, few have been evaluated in children.

Recently, a new drug class has emerged that targets deficiencies of GLP-1. One of the main glycemic mechanisms of action of the GLP-1 agonists such as exenatide is to enhance glucose disposal in the postprandial setting and improve glucose tolerance. In addition, exenatide can induce weight loss by decreasing appetite and slowing gastric motility.


Options:
A: Inclusion Criteria:

* 25 ≤ BMI ≤ 35
* Expressed desire for weight loss
* Accustomed to 3 main meals/day
* Consistent and stable body weight 3 months prior to study enrolment
* Commitment to avoid the use of other weight loss products during study
* Commitment to adhere to diet recommendation
* Females' agreement to use appropriate birth control methods during the active study period
* Subject declares in writing his/her consent to participate, understands requirements of the study and is willing to comply

Exclusion Criteria:

* Known sensitivity to the ingredients of the device
* Presence of any active gastrointestinal disease
* Malabsorption disorders (e.g. Coeliac disease)
* Pancreatitis
* Stenosis in the GI tract
* Bariatric surgery
* Abdominal surgery within the last 6 months prior to the study
* History of eating disorders like bulimia, anorexia nervosa
* History of renal disease
* History of nephrolithiasis
* History of cardiac diseases
* Osteoporosis
* Other serious organ or systemic diseases such as cancer, HIV, or diabetes mellitus
* Any medication that could influence GI functions such as antibiotics, laxatives, opioids, anticholinergics, or anti-diarrheals (must have stopped 3 months before study start)
* Pregnancy or nursing
* Any medication or use of products for the treatment of obesity (e.g., Orlistat, other fatbinder, fatburner, satiety products etc.)
* More than 3 hours serious sport activity per week
* History of abuse of drugs, alcohol or medication
* Smoking cessation within the 6 months prior to this study
* Inability to comply due to language difficulties
* Participation in similar studies or weight loss programs within the 6 months prior to this study
* Participation in other studies within the last 4 weeks
B: 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
C: 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.
D: Inclusion Criteria:

* Subjects must be between the ages of 13.00 and 17.99 at week 0 (Baseline).
* Subjects must have a BMI ≥ 95th percentile for age and gender using the CDC data (see Appendix), but must weigh less than 300 pounds (\<136 kilograms) when measured during the initial physical exam at week 0 (Baseline). BMI will be calculated as follows; weight in kilograms  \[height in meters\]2. This cutoff has been established due to the weight-bearing limits of the table used in performing the DXA scan. Once enrolled, if a subject's weight progresses above 300 pounds, s/he may continue in the study whether it is possible to perform DXA or not.
* Completion of informed consent/assent process

Exclusion Criteria:

* Known diabetes as defined by the American Diabetes Association criteria
* Prior drug therapy to treat diabetes or insulin insensitivity, including any form of insulin or insulin analogs; or any oral antidiabetic medication; acarbose, acetohexamide, chlorpropamide, glimepiride, glipizide, glyburide, metformin, pioglitazone, repaglinide, rosiglitazone, tolazamide, tolbutamide or troglitazone.
* Prior use of drugs to aid in weight loss, including but not limited to: Benzphetamine Hcl, Diethylpropion Hcl, Fenfluramine Hcl, Phendimetrazine Tartrate, Phentermine Hcl, Orlistat, Sibutramine Hcl Monohydrate, Didrex, Tenuate, Pondimin, Bontril-SR, Adipex-P, Fastin, Ionamin, Phentrol, Xenical, Meridia.
* Subject is currently taking the following medications at the time of the Screening visit: Cimetidine, amiloride, digoxin, furosemide, morphine, nifedipine, procainamide, ranitidine, triamterene, trimethoprim, vancomycin and quinidine, as these medications may increase metformin levels.
* Subjects will be excluded from the study if they have taken prescription-strength glucocorticoids (by any route) within three months of the screening visit. Topical glucocorticoids are acceptable if their strength is no greater than the equivalent of 1% hydrocortisone cream.
* History of any syndrome or medical disorder associated with significant obesity, including but not limited to: Prader Willi Syndrome, Bardet-Biedl Syndrome, Cohen Syndrome, Cushing syndrome or disease.
* Prior surgical therapy for obesity
* Subject to be excluded if s/he has attended a formal weight loss program within 6 months prior to the Screening visit.
* In the 6 months prior to Screening, subject has consumed alcohol more frequently than twice per week and/or subject has had more than three alcohol-containing beverages in a 24 hour period.
* Elevated creatinine (\> 1.2 mg/dl)
* Untreated disorders of thyroid function
* Elevated liver enzymes (Alanine Aminotransferase \[ALT\] or Aspartate Aminotransferase \[AST\]) \> 80 (approximately 2 times upper limit of normal)
* Mobility impairment that prevents full participation in recommended physical activity
* Other serious medical condition that the Principal Investigator or Lead Site Investigator determines may put the patient at undue risk if enrolled in the study
* Unable to comply with the protocol in the opinion of the Principal Investigator or the Lead Site Investigator
* Subjects with child-bearing potential who are unwilling to remain abstinent or use an effective method of birth control
* Previous pregnancy

Answer: B