Please select the eligibility criteria that correspond to the clinical trial below.
Title: Treatment of Metabolic Abnormalities in Patients With Schizophrenia: Adjunctive Low-dose Metformin in Patients With Schizophrenia and Metabolic Abnormalities
Brief Summary: Metformin has been used for alleviating metabolic abnormalities in patients with schizophrenia. Until now, the lowest dose of metformin to treat metabolic abnormalities in clozapine-treated patients is 1000 mg/d. The aim of this study was to determine whether a lower dosage of metformin, such as 500 mg/d, is effective for improving metabolic profiles in clozapine-treated patients with pre-existing metabolic abnormalities.

Methods:

In this 12-week, randomized, double-blind, placebo-controlled trial, metformin 500 mg/d or 1000 mg/d or a placebo was prescribed to clozapine-treated patients with schizophrenia having pre-existing metabolic abnormalities. The recruited patients underwent physical and laboratory evaluations at week-4, week-8, and week-12.


Options:
A: Inclusion Criteria:

* Inclusion Criteria are:

  1. DSM-IV diagnosis of Schizophrenia or schizoaffective disorder
  2. Age: 18-64
  3. Regular half pack a day smokers
  4. Score of at least 4 on the Nicotine Dependency Test

     Exclusion Criteria:

     Exclusion Criteria are:

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  1. Seizure disorders, other Neurologic illnesses, or a family history of seizures
  2. A medical condition that could manifest psychiatrically
  3. Currently experiencing a depressive episode
  4. Active substance abuse
  5. Currently receiving bupropion
  6. Pregnant women
  7. Children (\<18 years of age)
  8. Two consecutive sodium levels of 130 mmol/L or less
B: 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).
C: Inclusion Criteria:

1. patients diagnosed with schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
2. aged 20-65 years
3. had taken clozapine for at least 3 months
4. had at least one of the following metabolic abnormalities: BMI ≥ 24; WC \> 90 cm (men) or 80 cm (women); fasting serum TG level ≥ 150 mg/dL; fasting serum HDL-C level ≤ 40 mg/dL (men) or 50 mg/dL (women); systolic BP ≥ 130 or diastolic BP ≥ 85 mm Hg; current use of antihypertensive agents; and FPG level = 100-126 mg/dL.

Exclusion Criteria:

1. history of diabetes mellitus
2. current use of hypoglycemic or hypolipidemic agents
3. pregnancy
4. allergy to metformin
5. a creatinine level \> 1.4 ng/dL
6. an abnormal liver function test result
7. chronic cardiopulmonary insufficiency.
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: C