Please select the eligibility criteria that correspond to the clinical trial below.
Title: Metformin in the Treatment of Antipsychotic-Induced Weight Gain in Schizophrenia (METS) - Pilot Study
Brief Summary: This study will test the usefulness of the medication metformin in treating people with schizophrenia or schizoaffective disorder who are overweight and also taking antipsychotic medications.


Options:
A: Inclusion Criteria:

* Outpatients with a diagnosis of schizophrenia or schizoaffective disorder, as defined by DSM-IV-TR criteria and confirmed by the Structured Clinical Interview for DSM-IV (SCID)
* Duration of illness greater than 1 year, as defined by having initiated antipsychotic treatment at least 1 year prior to study entry
* Adequate decisional capacity to make a choice about participating in this research study
* Body mass index (BMI) at or greater than 27
* Currently being treated with one or a combination of two antipsychotic medications (typical or atypical) and on that drug regimen for at least 2 months prior to study entry, with stable dosages for at least 1 month
* If taking antidepressants, mood stabilizers, or anxiolytics, the dose must be stable for at least 1 month prior to study entry
* Willing to use an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the study. Acceptable methods include oral, injectable, or implanted contraceptives; intrauterine devices or barrier methods such as condoms; and diaphragms and spermicides.

Exclusion Criteria:

* Inpatient status
* Clinical Global Impression Severity (CGI-S) score greater than 6
* Currently being treated with more than two antipsychotic medications
* Fasting glucose greater than 125
* Diagnosis of diabetes mellitus or treatment with insulin or oral hypoglycemics
* Previous or current treatment with metformin
* Diagnosis of congestive heart failure
* Renal impairment, as defined by a serum creatinine level greater than 1.5 in males or greater than 1.4 in females, or creatinine estimated glomerular filtration rate (GFR) outside of normal limits
* Hepatic disease, as defined by aspartate transaminase (AST), alanine transaminase (ALT), or c-glutamyl transferase (CGT) greater than 1.5 times upper limit of normal (ULN), or total bilirubin greater than 1.2 times ULN
* Metabolic acidosis, as defined by serum carbon dioxide less than the lower limit of normal
* Known hypersensitivity to metformin
* Pregnant or breastfeeding
* Recent (in the past 30 days) or scheduled radiological studies involving iodinated contrast material
* Alcohol abuse or dependence within the past month, as determined by the SCID
* Other serious and unstable medical condition in the judgment of the investigator
* Diagnosis of mental retardation, delirium, or dementia, as defined by DSM-IV-TR
* Failed to discontinue 4 weeks prior to study entry any medication used for weight loss
* Concurrent treatment with certain drugs that are known to increase metformin blood levels should be discussed with the Project Medical Officer.
B: Inclusion Criteria:

* Informed oral and written consent
* Diagnosed with schizophrenia, schizotypal disorder or paranoid psychosis according to the criteria of ICD10 (International Classification of Diseases, World Health Organization) or the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, the American Psychiatric Association)
* and on stable antipsychotic treatment with either clozapine or olanzapine for at least 6 months (without dose change for at least 30 days)
* Stable co-medications for at least 30 days.
* Age ≥18 years and ≤65 years
* Stable weight (defined as less than 5% change in weight over the last 3 month before inclusion)
* BMI ≥27 kg/m2
* Dysglycaemia (IFG, i.e. fasting plasma glucose level from 6.1 mmol/L to 6.9 mmol/L or IGT, i.e. two-hour glucose levels \> 7.8 mmol/L on the 75-g oral glucose tolerance test with a fasting plasma glucose of less than 7.0 mmol/L and HbA1c \< 48 mmol/mol or HbA1c: 43 mmol/mol ≤ HbA1c ≤ 47 mmol/mol)

Exclusion Criteria:

* Compulsory treatment
* Females of child bearing potential who are pregnant, breast-feeding or have intention of becoming pregnant or are not using adequate contraceptive measures
* Subjects treated with corticosteroids or other hormone therapy (except estrogens)
* Any active substance abuse or dependence for the past 6 months (except for nicotine)
* Impaired hepatic function (liver transaminases \>2 times upper normal limit)
* Impaired renal function (se-creatinine \>150 μM and/or macroalbuminuria)
* Impaired pancreatic function (acute or chronic pancreatitis and/or amylase \>2 times upper normal limit)
* Cardiac problems defined as decompensated heart failure (NYHA class III or IV), unstable angina pectoris and/or myocardial infarction within the last 12 months
* Uncontrolled hypertension (systolic blood pressure \>180 mmHg, diastolic blood pressure \>100 mmHg)
* Any condition that the investigator feels would interfere with trial participation
* Receiving any investigational drug within the last 3 months
* Use of weight-lowering pharmacotherapy within the preceding 3 month
* Type 1 or 2 diabetes with HbA1c \> 6.5%

Also a group of healthy controls (n=10) will have the baseline examinations done. The healthy controls will be matched to our participants in regards to gender, BMI and age. The same inclusion and exclusion criteria will apply for these controls, except these participants are not allowed to have known psychiatric illness, receive anti-psychotic medications, or have a family history of type 2 diabetes (2 generations).
C: Inclusion Criteria:

* Adolescents and Adults ages 12-59 with a diagnosis of Schizophrenia, Schizoaffective Disorder, Schizophreniform, Bipolar I, Bipolar II, Bipolar NOS or Psychotic Disorder NOS, Autism Spectrum Disorder
* Patients will be currently treated with antipsychotics

Patients will qualify for entry if they meet the following weight criteria:

1. The patient has gained 7% of their weight since beginning of treatment with one or more of the current antipsychotics.
2. The patient has had an increase of 7% of their weight during the last year while being treated with antipsychotics.
3. The patient has a BMI of 30 or more and has gained 10 lbs or more in the past 8 months while being treated with antipsychotic medications.
4. The patient has a BMI of 35 or greater at the current time, and his chart shows a history of consistent weight gain over the past 1 to 3 years during treatment with antipsychotics.

   .

   Exclusion Criteria:
   * Subjects will be excluded if they have asthma, peptic ulcer disease (diseases which may be exacerbated by a histamine analog), or history of pheochromocytoma or peptic ulcer disease. Patients will be excluded if they are prescribed medications known to affect body weight or glucose-lipid metabolism, such as prescription or over the counter medications taken for the purpose of weight reduction. Subjects who are currently treated with metformin, for less than 6 months and have shown recent weight change on metformin. Patients on thyroid replacement therapy or lipid-lowering agents whose dosage has changed by more than 50 % in the past month will be excluded. If they are relatively stable doses of these medications they will not be excluded. Patients who are on lipid lowering medication, thyroid replacement medication, or diabetes medication, (excluding metformin), must remain on these medications throughout the period of the study. Females who are pregnant or breast feeding will be excluded.
D: Inclusion Criteria:

* diagnosis of schizophrenia by the International Classification of Diseases 10th Revision (ICD-10);
* age between 18 and 65 years old;
* on stable antipsychotic medication treatment for at least one month;
* BMI \> 28 kg/m2 according to BMI criterion for obesity in the Chinese population ， or BMI\>27 kg/m2 in the presence of dyslipidemia, or male with waist circumference over 90cm;
* smoking at least 10 cigarettes daily for one year or longer;
* desire to lose weight and quit smoking.

Exclusion Criteria:

* Binge eating or other eating disorders;
* Current use of weight loss or antidiabetic medications;
* Current substance use (except nicotine or caffeine);
* Elevated hepatic transaminase levels (\>2.5x normal range);
* Clinically significant Thyroid Stimulating Hormone（TSH） and/or thyroxine4（T4） abnormalities;
* History of seizure disorder;
* History of unstable cardiac problems or other unstable medication conditions;
* Being pregnant or nursing (for women).

Answer: A