Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effects of Metformin on Energy Intake, Energy Expenditure, and Body Weight in Overweight Children With Insulin Resistance
Brief Summary: This study will examine the safety and effectiveness of the medicine metformin to help overweight children control their food intake, weight, insulin, cholesterol, and triglyceride (blood fat) levels. Obesity and high insulin levels can lead to high blood pressure, diabetes, high cholesterol and triglyceride levels and heart disease. Metformin-approved by the Food and Drug Administration to treat adults with type 2 diabetes mellitus-helps lower insulin levels and may control weight gain in adults.

Overweight children 6 to 11 years old who are in general good health may be eligible for this study. Children will be studied at the National Institutes of Health in Bethesda, Maryland. Candidates will have a medical history and physical examination and fasting blood test, and will provide a 7-day record of their food intake as part of the screening process. Those enrolled will be randomly assigned to receive either metformin or placebo (a look-alike tablet with no active medicine) twice a day for a six month period. After the 6 month study period, all children will be offered the opportunity to take metformin for another 6 months.

Participants will be hospitalized for 2-3 days for the following procedures: history and physical examination; fasting blood test; several urine collections; X-ray studies to determine bone age and amount of body fat and muscle; magnetic resonance imaging (MRI) scan to measure body fat; "hyperglycemic clamp study" to evaluate insulin resistance; food intake testing; nutrition consultation; resting metabolic rate; and a "doubly labeled water" test.

For the hyperglycemic clamp study, a catheter (thin flexible tube) is inserted into a vein in each arm. A sugar solution is given through one tube and blood samples are drawn every 5 minutes through the other to measure insulin. For the food intake testing, the child is asked about his or her hunger level, then given various foods he or she may choose to eat, then questioned again at various intervals both during and after finishing eating about his or her hunger level. The doubly labeled water study involves drinking "heavy water" (water which is enriched to have special kinds of hydrogen and oxygen). Urine specimens are collected 2, 3 and 4 hours after drinking the water. The child also drinks a special milk shake called a Scandishake and repeats the calorie intake and hunger study. (Two food intake studies are done on separate days.) One week after the heavy water test, additional urine samples are collected one week later.

After completing the tests, the child will begin treatment with metformin or placebo, plus a daily vitamin tablet. Participants will be followed once a month with a brief history and physical examination, including a blood test. After 6 months, all of the tests described above will be repeated. All children who complete the second round of tests-both those who took metformin and those who took placebo-will be offered metformin for an additional 6 months and will be seen once a month for follow-up evaluations. Parents will not be told which children received metformin and which received placebo until all children in the study complete the first 6 months of the trial.


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 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 greater than or equal to 6 and less than 13 years.

Pre-pubertal or having at most early puberty (breast Tanner I, II or III for girls, testes size less than or equal to 8 mL for boys).

Hyperinsulinemia, defined as fasting insulin concentration greater than or equal to 15 mIU/mL. The insulin level must be greater than or equal to 15 at either the NIH Clinical Center lab or the NIDDK lab at PIMC in Phoenix.

Obesity, defined as body mass index greater than or equal to 95th percentile determined by NHANES I age and sex specific data.

Subjects must have fasting plasma glucose less than 126 mg/dl

Subjects must have glycosylated hemoglobin (HgbA1C) of less than or equal to 6.5%.

Females who begin menstruating (or who are at risk for pregnancy) during the study must have a negative pregnancy test and must use an effective method of contraception if they are engaging in sexual intercourse.

EXCLUSION CRITERIA:

Baseline creatinine greater or equal to 1.0 mg/dl.

Significant cardiac or pulmonary disease likely to or resulting in hypoxia or decreased perfusion.

Hepatic disease with elevated liver function tests (ALT or AST) greater than or equal to 1.5 the upper limits of normal.

An alcohol history concerning for development of hepatic toxicity.

Pregnancy.

Evidence for Type 2 diabetes, including fasting plasma glucose greater than or equal to 126 mg/dl or HgbA1C greater than 6.5%.

Weight loss of greater than 2% of bodyweight within the past 6 months.

Presence of other endocrinologic disorders leading to obesity (e.g. Cushing's Syndrome).

Individuals who have, or whose parent or guardians have current substance abuse or a psychiatric disorder or other condition that, in the opinion of the investigators, would impede competence or compliance or possibly hinder completion of the study.

Recent use (within six months) of anorexiant medications.

Individuals receiving medical treatment other than diet for hypertension or dyslipidemia.

Individuals with evidence of precocious puberty.
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: C