Potential Intervention Strategy With Folic Acid and Vitamin B12 in Patients With Schizophrenia

Study Overview
=================
Brief Summary
-----------------
The investigators study aims are: To investigate folate, vitamin B12, and homocysteine levels in patients with schizophrenia. To evaluate the relationships among folate, vitamin B12, and homocysteine levels, genetic variants of one-carbon cycle pathway, psychopathology, including positive symptoms, negative symptoms, and cognition, and metabolic abnormalities in patients with schizophrenia. For patients with low folate levels, the investigators would like to conduct a 24-week double-blinded, placebo-controlled of folic acid (5 mg/d) and vitamin B12 (500 ug/d) supplementation study to know whether combination of folic acid and vitamin B12 can improve patients' psychopathology or metabolic profiles, and the effects of genetic variants in one-carbon cycle pathway on treatment response.

Official Title
-----------------
Relationships of One-carbon Cycle Pathway With Psychopathology and Metabolic Abnormalities in Patients With Schizophrenia and Potential Intervention Strategy With Folic Acid and Vitamin B12

Conditions
-----------------
Schizophrenia

Intervention / Treatment
-----------------
* Dietary Supplement: folic acid 5 mg/cap
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 20-65 year-old. Fulfill DSM-IV-TR diagnosis of schizophrenia. Be treated with an antipsychotic agent for at least 6 months or at a stable dose for at least 3 months. Patients with folate deficiency or insufficiency, and PANSS score at least 60 or more in the first phase screening. Folate deficiency and insufficiency (low folate level) are defined as serum folate < 6.8 nmol/L (3 ng/mL) and <= 13.5 nmol/L (6 ng/mL), respectively. Exclusion Criteria: Medically unstable. Currently taking vitamin supplementation. Pregnancy or lactation. Test positive of urine drug screen Megaloblastic anemia due to folate deficiency; Patients with parkinsonism (score of > 12 on the Simpson-Angus Scale); History of alcohol or other substances use disorder in past 3 months; History of significant neurological illness; Creatine>1.4 ng/dl.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: folic acid 5 mg/cap<br>folic acid 5 mg/d and vitamin B12 500 ug/d | Dietary Supplement: folic acid 5 mg/cap<br>* the intervention includes folic acid 5 mg/d and vitamin B12 500 ug/d<br>* Other names: vitamine B12 500 ug/cap;|
| Placebo Comparator: placebo<br>placebo | Other: Placebo<br>* placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and Negative Syndrome Scale (PANSS) | We used PANSS to evaluate patients' psychopathology at baseline, week-2, 4, 8, 12, 16, 20, and 24. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CogStat neuropsychological test, including speed of processing, attention, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition | CogStat will be used to test patients' cognitive function, including speed of processing, attention, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition, at baseline and week-24. | 24 weeks | 
| blood pressure, mmHg | Blood pressure will be checked at week 4, 12, and 24. | 24 weeks | 
| waist circumference, cm | Waist circumference will be checked at week 4, 12, and 24. | 24 weeks | 
| triglyceride, mg/dL | Triglyceride will be checked at week 4, 12, and 24. | 24 weeks | 
| high density lipoprotein cholesterol (HDL-C), mg/dL | HDL-C will be checked at week 4, 12, and 24. | 24 weeks | 
| fasting blood sugar level, mg/dL | fasting blood sugar level will be checked at week 4, 12, and 24. | 24 weeks |