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:

* 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
B: Inclusion Criteria:

* Age: 18 - 65 years
* Diagnosis of the schizophrenia spectrum (ICD-10: F20.x, F25.x)both in-patients and out-patients will be included
* Current and unchanged treatment with at least one antipsychotic drug (FGA and/or SGA and/or depot treatment)
* BMI ≥30 kg/m2
* HbA1c \< 6,5 %

Exclusion Criteria:

* Substance dependence (ICD-10: F1x.2 (apart from nicotine addiction F17.2))
* Diabetes or HbA1c ≥6.5%
* Contraindications to MRI (metal implants, pacemakers, severe claustrophobia, ≥150 kg (max. bed weight in the MRI scanner))
* Previous head trauma with a loss of consciousness for more than 5 minutes
* Pregnancy (screened by urine human chorionic gonadotropin (hCG),lactation or no acceptance to use effective contraception during the intervention period
* Severe somatic disease, including inflammatory bowel disease and chronic ketoacidosis
* Allergy to exenatide
* Coercive measures according the Danish Law of Psychiatry
* conditions that according to sponsor are not congruous with participation in the study
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:

* 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).

Answer: A