Folate Supplementation in Schizophrenia

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Folate; Drug: Placebo

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

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Schizophrenia, any subtype
2. Ages 18-68
3. Male or female
4. 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
5. Stable antipsychotic dose for > 6 weeks
6. Capable of providing informed consent

Exclusion Criteria:

1. Unstable medical illness
2. Substance abuse
3. Megaloblastic anemia
4. Non-english speaking

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Alliance for Research on Schizophrenia and Depression
• Investigators: Principal Investigator: Donald C. Goff, M.D., Massachusetts General Hospital

Publications and helpful links

General Publications

• Hill M, Shannahan K, Jasinski S, Macklin EA, Raeke L, Roffman JL, Goff DC. Folate supplementation in schizophrenia: a possible role for MTHFR genotype. Schizophr Res. 2011 Apr;127(1-3):41-5. doi: 10.1016/j.schres.2010.12.006. Epub 2011 Feb 21.

Study record dates

Study Major Dates

• Study Start: December 1, 2003
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: November 3, 2005
• First Submitted That Met QC Criteria: November 3, 2005
• First Posted (Estimate): November 7, 2005

Study Record Updates

• Last Update Posted (Actual): April 5, 2018
• Last Update Submitted That Met QC Criteria: March 9, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Schizophrenia; Folate; Negative Symptoms
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Micronutrients; Vitamins; Hematinics; Folic Acid; Vitamin B Complex
• Other Study ID Numbers: 2004P-000495