Folate Supplementation in Schizophrenia

• ClinicalTrials.gov Identifier: NCT00249288
• Recruitment Status: Completed
• First Posted: November 7, 2005
• Results First Posted: August 6, 2014
• Last Update Posted: April 5, 2018
• Sponsor: Massachusetts General Hospital
• Collaborator: National Alliance for Research on Schizophrenia and Depression
• Information provided by (Responsible Party): Donald C. Goff, MD, Massachusetts General Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Schizophrenia	Drug: Folate; Drug: Placebo	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Folate Supplementation in Schizophrenia
• Study Start Date: December 2003
• Actual Primary Completion Date: June 2008
• Actual Study Completion Date: June 2008

Arms and Interventions

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 Name: 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

Outcome Measures

Primary Outcome Measures :

1. Correlation Between Baseline Blood Folate and Smoking Status [ Time Frame: Baseline ]
   Baseline blood folate lab levels are reported by smoking status.
2. Correlation Between Baseline Blood Folate and MTHFR Genotype [ Time Frame: Baseline ]
   Baseline blood folate lab levels are reported by MTHFR genotype.
3. Correlation Between Baseline Blood Folate Levels and Dietary Intake [ Time Frame: Baseline ]
   Baseline blood folate lab levels and dietary intake levels are reported.
4. Efficacy of Folate Supplementation for Reducing Negative Symptoms as Measured by the SANS Modified Total [ Time Frame: 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.
5. Correlation Between Baseline Serum B12 Levels and Smoking Status [ Time Frame: Baseline ]
   Baseline serum B12 lab levels are reported by smoking status.
6. Correlation Between Baseline Homocysteine Levels and Smoking Status [ Time Frame: Baseline ]
   Baseline blood homocysteine lab levels are reported by smoking status.
7. Correlation Between Baseline Blood B12 Levels and MTHFR Genotype [ Time Frame: Baseline ]
   Baseline blood B12 lab levels are reported by MTHFR genotype.
8. Correlation Between Baseline Blood Homocysteine Levels and MTHFR Genotype [ Time Frame: Baseline ]
   Baseline blood homocysteine lab levels are reported by MTHFR genotype.
9. Correlation Between Baseline Serum B12 Levels and Dietary Intake [ Time Frame: Baseline ]
   Baseline serum B12 lab levels and dietary intake levels are reported.
10. Correlation Between Baseline Blood Homocysteine Levels and Dietary Intake [ Time Frame: Baseline ]
    Baseline blood homocysteine lab levels and dietary intake levels are reported.
11. Correlation Between Baseline Blood Folate or B12 Levels and Dietary Intake [ Time Frame: Baseline ]
    Baseline blood folate and B12 lab levels and dietary intake levels are reported.

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Massachusetts General Hospital

National Alliance for Research on Schizophrenia and Depression

Investigators

• Principal Investigator: Donald C. Goff, M.D.; Massachusetts General Hospital

More Information

Additional Information:

Related Info 

Publications of Results:

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.

• Responsible Party: Donald C. Goff, MD, Director of the Schizophrenia Clinical and Research Program, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00249288
• Other Study ID Numbers: 2004P-000495
• First Posted: November 7, 2005
• Results First Posted: August 6, 2014
• Last Update Posted: April 5, 2018
• Last Verified: March 2018

Keywords provided by Donald C. Goff, MD, Massachusetts General Hospital:

Schizophrenia; Negative Symptoms; Folate

Additional relevant MeSH terms:

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Folic Acid; Vitamin B Complex; Hematinics; Vitamins; Micronutrients; Physiological Effects of Drugs