Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase 2 Study of Melatonin Adjunct to Olanzapine for Prevention of Olanzapine-associated Metabolic Side Effects.
Brief Summary: The purpose of this study is to determine whether melatonin can prevent metabolic side effects of olanzapine such as weight gain, elevated glucose concentrations and lipid abnormalities.


Options:
A: Inclusion Criteria:

phase 1

* fulfilled DSM-IV criteria of schizophrenia or schizoaffective disorder
* 18-65 year of age
* receiving clozapine for at least 6 months.

phase 2 are those in phase 1 and met the following

* overweight and obese (BMI ≧ 24)
* one or more metabolic dysregulation, such as abdominal obesity (waist circumference \> 90 cm, in men and \> 80 cm, in women
* fasting hypertriglyceridemia, (≥ 150 mg/dL)
* low fasting HDL levels (\< 40 mg/dL in men and \< 50 mg/dL in women)
* high blood pressure (≥ 130/ ≥ 85 mm Hg or current treatment with antihypertensive medication).

The exclusion criteria are the following:

* current use of hypoglycemic or hypolipidemic agents
* FPG levels ≥ 126 mg/dL
* women who are pregnant
* known allergy or contraindicated to metformin (including Creatine\>1.4 ng/dl abnormal liver function test; chronic cardiopulmonary insufficiency).

Exclusion Criteria:

phase 2

* current use of hypoglycemic or hypolipidemic agents
* FPG levels ≥ 126 mg/dL
* women who are pregnant
* known allergy or contraindicated to metformin (including Creatine\>1.4 ng/dl abnormal liver function test
* chronic cardiopulmonary insufficiency).
B: 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.
C: Inclusion Criteria:

* Age 18-65 year
* First episode schizophrenia (DSM-IV-TR)
* Ability to take medicine orally
* Eligible for starting olanzapine

Exclusion Criteria:

* Married women who are at reproductive age
* History of taking olanzapine in the recent 3 months
* History of allergy or intolerance to olanzapine
* History of significant head trauma ( causing loss of consciousness more than 5 minutes or neurological or cognitive sequels)
* Liver, kidney, cerebrovascular or cardiovascular disease
* Diabetes, metabolic syndrome
* Cancer
* Using antiepileptic (other than benzodiazepines for sleep) , antihypertensive, anticoagulant, anti-platelet drugs
* Using inhibitors or stimulants of hepatic isoenzymes that metabolize melatonin or olanzapine (e.g. omeprazole. rifampin, fluvoxamine, ciprofloxacin, carbamazepine, modafinil)
* Delirium
* Need for administration of other antipsychotics
* Substance abuse
D: Inclusion Criteria:

* Participants must have a diagnosis of bipolar I disorder and display an acute manic or mixed episode (with or without psychotic features) or a diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition - Text Revision (DSM-IV-TR)and confirmed by the Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime (K-SADS-PL).
* Participants with a diagnosis of schizophrenia must obtain a Brief Psychiatric Rating Scale for Children (BPRS-C) total score \>30, with a minimum score of 3 on at least one of the following items at both screening and randomization - hallucinations, delusions, peculiar fantasies.
* Participants with a diagnosis of bipolar I disorder must have a Young Mania Rating Scale (YMRS) total score greater than or equal to 15 at both screening and randomization.
* Has given assent (when applicable); and has a parent or authorized legal representative who has given informed consent, is reliable, has a level of understanding sufficient to permit participant to perform all tests and examinations required by the protocol, and understands the nature of the study.

Exclusion Criteria:

* History of mental retardation, current comorbid autism, or current comorbid Pervasive Developmental Disorder.
* Have DSM-IV-TR substance (except nicotine and caffeine) dependence within the past 30 days prior to randomization.
* Been judged clinically to be at any suicidal risk.
* History of allergic reaction or hypersensitivity to olanzapine.
* Receiving current pharmaceutical treatment for weight management or are participating in a structured behavioral diet and/or exercise weight loss program.
* Other antipsychotics, mood stabilizers, or anticonvulsants (for mood stabilization) used for the primary study conditions (bipolar I disorder or schizophrenia)
* Have acute, serious, or unstable medical conditions
* Have any illness such that death is anticipated within 1 year or intensive care unit hospitalization for the illness is anticipated within 12 months (365 days).
* Have had one or more seizures without a clear and resolved etiology.
* Baseline alanine aminotransferase (ALT) values greater than or equal to 2 times the upper limit of normal (ULN) of the performing laboratory or aspartate aminotransferase (AST) values greater than or equal to 2 times the ULN or total bilirubin values greater than or equal to 1.5 times the ULN at screening.
* Have leukopenia or history of leukopenia without a clear and resolved etiology or known history of agranulocytosis (absolute neutrophil count \<500 cubic millimeter \[mm\^3\], \<0.5 GI/L, or \<0.5 10E\^3/microliters \[μL\]) during the participant's lifetime.
* Prolactin level of \>200 nanograms per milliliter (ng/mL) \[\>200 micrograms per liter (ug/L), or \>4228 milli-International unit per liter (mIU/L)\] at screening.
* Have QTc (Bazett's) \>450 milliseconds (males) or \>460 milliseconds (females) at screening.
* Previously been randomized in this study and/or participated in a clinical trial of another investigational drug, including olanzapine, within 1 month (30 days) prior to screening.
* Currently prescribed olanzapine for greater than or equal to 5 days within 1 month (30 days) prior to screening.
* Are investigator site personnel directly affiliated with this study and/or their immediate families OR are employed by or representatives of Lilly.
* Pregnant or nursing.
* Have received treatment within the last 30 days with an investigational new drug that has not received regulatory approval for any indication at the time of study entry.
* Treatment with clozapine within 14 days prior to randomization.
* Participants who have used olanzapine (that is, oral olanzapine, intramuscular \[IM\] olanzapine, or olanzapine orally disintegrating tablets) and have had treatment withdrawn due to clinically significant and/or intolerable adverse effects, or who have exhibited a lack of efficacy/response to treatment to olanzapine including treatment resistance.

Answer: C