Folate Supplementation in Schizophrenia

Phase 4

Completed

Conditions: Schizophrenia

Interventions: Drug: Placebo
Drug: Folate

Registration Number: NCT00249288

Lead Sponsor: Massachusetts General Hospital

Brief Summary: This study aims to examine factors potentially contributing to differences in blood folate, homocysteine or B12 levels between schizophrenia patients, to test the hypothesis that low folate is associated with negative symptoms, and to examine the efficacy of folate supplementation for reducing negative symptoms.

Detailed Description: This study is a three-month, placebo-controlled trial of folate 2mg/d in 50 schizophrenia patients who score at least a 3 (moderate or greater severity) on at least one of the SANS global assessment subscales, with the exception of the attention global assessment subscale. The specific aims of this study are:

* To examine factors potentially contributing to differences in blood folate, homocysteine or B12 levels between patients at baseline, including dietary intake and cigarette smoking.

* To test the hypothesis that low folate is associated with negative symptoms by examining correlations between red blood cell folate concentrations and clinical ratings of negative symptoms and by comparing folate concentrations in deficit syndrome versus non-deficit syndrome patients. We will also control for dietary intake cigarettes smoking, gender, and age.

* To examine the efficacy of folate supplementation for reducing negative symptoms

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 46

Inclusion Criteria

Schizophrenia, any subtype
Ages 18-68
Male or female
A score at least a 3 (moderate or greater severity) on at least one of the SANS global assessment subscales, with the exception of the attention global assessment subscale
Stable antipsychotic dose for > 6 weeks
Capable of providing informed consent

Exclusion Criteria

Unstable medical illness
Substance abuse
Megaloblastic anemia
Non-english speaking

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants will receive a 2 mg/ day dose of placebo, for 12 weeks
Folate	Folate	Participants will receive a 2 mg/ day dose of folate, for 12 weeks

Primary Outcome Measures

Name	Time	Method
Correlation Between Baseline Blood Folate and Smoking Status	Baseline	Baseline blood folate lab levels are reported by smoking status.
Correlation Between Baseline Blood Folate and MTHFR Genotype	Baseline	Baseline blood folate lab levels are reported by MTHFR genotype.
Correlation Between Baseline Blood Folate Levels and Dietary Intake	Baseline	Baseline blood folate lab levels and dietary intake levels are reported.
Efficacy of Folate Supplementation for Reducing Negative Symptoms as Measured by the SANS Modified Total	Baseline score vs. week 12 score	The change from baseline to week 12 on the scale for the assessment of negative symptoms (SANS) modified total score. Total SANS scores range from 0-100. The SANS is comprised of 5 sub-scales: Affective Flattening or Blunting (score range 0-35), Alogia (score range 0-20), Avolition-Apathy (score range 0-15), Anhedonia-Asociality (score range 0-20), and Attention (0-10). For each sub-scale, the higher the score the more prominent the negative symptoms were. The total score was computed by adding all the sub-scale total scores. To compute change in scores, baseline scores were subtracted from week 12 scores, resulting in a change score. Lower values signify greater improvement (i.e. week 12 score was lower than baseline score). The SANS modified total score is the SANS total score minus the Attention subscale.
Correlation Between Baseline Serum B12 Levels and Smoking Status	Baseline	Baseline serum B12 lab levels are reported by smoking status.
Correlation Between Baseline Homocysteine Levels and Smoking Status	Baseline	Baseline blood homocysteine lab levels are reported by smoking status.
Correlation Between Baseline Blood B12 Levels and MTHFR Genotype	Baseline	Baseline blood B12 lab levels are reported by MTHFR genotype.
Correlation Between Baseline Blood Homocysteine Levels and MTHFR Genotype	Baseline	Baseline blood homocysteine lab levels are reported by MTHFR genotype.
Correlation Between Baseline Serum B12 Levels and Dietary Intake	Baseline	Baseline serum B12 lab levels and dietary intake levels are reported.
Correlation Between Baseline Blood Homocysteine Levels and Dietary Intake	Baseline	Baseline blood homocysteine lab levels and dietary intake levels are reported.
Correlation Between Baseline Blood Folate or B12 Levels and Dietary Intake	Baseline	Baseline blood folate and B12 lab levels and dietary intake levels are reported.

Secondary Outcome Measures

Name	Time	Method
Correlations Between Baseline Blood Folate and Clinical Ratings of Negative Symptoms by Comparing Lab Levels in Deficit Syndrome Versus Non-deficit Syndrome Patients	Baseline	Baseline blood folate lab levels are reported by deficit syndrome status.
Correlations Between Baseline Blood B12 Levels and Clinical Ratings of Negative Symptoms by Comparing Lab Levels in Deficit Syndrome Versus Non-deficit Syndrome Patients	Baseline	Baseline blood B12 lab levels are reported by deficit syndrome status.
Correlations Between Baseline Blood Homocysteine Levels and Clinical Ratings of Negative Symptoms by Comparing Lab Levels in Deficit Syndrome Versus Non-deficit Syndrome Patients	Baseline	Baseline blood homocysteine lab levels are reported by deficit syndrome status.