Folate Supplementation in Schizophrenia

Study Overview
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Brief Summary
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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
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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

Official Title
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Folate Supplementation in Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Folate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 68 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Folate<br>Participants will receive a 2 mg/ day dose of folate, for 12 weeks | Drug: Folate<br>* Folic acid taken as 2, 1mg capsule daily for 12 weeks<br>* Other names: Folate or folic acid;|
| Placebo Comparator: Placebo<br>Participants will receive a 2 mg/ day dose of placebo, for 12 weeks | Drug: Placebo<br>* Placebo taken as 2, 1mg capsule daily for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation Between Baseline Blood Folate and Smoking Status | Baseline blood folate lab levels are reported by smoking status. | Baseline | 
| Correlation Between Baseline Blood Folate and MTHFR Genotype | Baseline blood folate lab levels are reported by MTHFR genotype. | Baseline | 
| Correlation Between Baseline Blood Folate Levels and Dietary Intake | Baseline blood folate lab levels and dietary intake levels are reported. | Baseline | 
| Efficacy of Folate Supplementation for Reducing Negative Symptoms as Measured by the SANS Modified Total | 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. | Baseline score vs. week 12 score | 
| Correlation Between Baseline Serum B12 Levels and Smoking Status | Baseline serum B12 lab levels are reported by smoking status. | Baseline | 
| Correlation Between Baseline Homocysteine Levels and Smoking Status | Baseline blood homocysteine lab levels are reported by smoking status. | Baseline | 
| Correlation Between Baseline Blood B12 Levels and MTHFR Genotype | Baseline blood B12 lab levels are reported by MTHFR genotype. | Baseline | 
| Correlation Between Baseline Blood Homocysteine Levels and MTHFR Genotype | Baseline blood homocysteine lab levels are reported by MTHFR genotype. | Baseline | 
| Correlation Between Baseline Serum B12 Levels and Dietary Intake | Baseline serum B12 lab levels and dietary intake levels are reported. | Baseline | 
| Correlation Between Baseline Blood Homocysteine Levels and Dietary Intake | Baseline blood homocysteine lab levels and dietary intake levels are reported. | Baseline | 
| Correlation Between Baseline Blood Folate or B12 Levels and Dietary Intake | Baseline blood folate and B12 lab levels and dietary intake levels are reported. | Baseline | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Folate, Schizophrenia, Negative Symptoms