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CompletedNCT00249288Updated Apr 5, 2018Results posted

Folate Supplementation in Schizophrenia

A Phase 4 interventional study of Folate and Placebo in Schizophrenia, sponsored by Massachusetts General Hospital. Completed at 1 site in United States. Open to participants aged 18 Years to 68 Years. Per ClinicalTrials.gov, last updated 2018-04-05.

Sponsored by Massachusetts General Hospital · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
46
Allocation
Randomized
Ages
18 Years to 68 Years
Sex
All
01

Study 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.

Read the 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
02

Conditions studied

  • Schizophrenia

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Keywords

  • Schizophrenia
  • Negative Symptoms
  • Folate
03

In context

Schizophrenia

3,471 studies on the registry are indexed under Schizophrenia; 472 are open to participants now.

This study's enrollment of 46 is below the median of 70 across 2,872 interventional studies indexed under Schizophrenia.

Browse Schizophrenia studies →

Lead sponsor

Massachusetts General Hospital is the lead sponsor of 2,536 studies on the registry; 446 are open to participants now.

Of its 214 completed or terminated interventional studies of FDA-regulated products, 161 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 68 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

Exclusion Criteria:

  1. Unstable medical illness
  2. Substance abuse
  3. Megaloblastic anemia
  4. Non-english speaking
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
46 participants (actual)

Study arms

  • Experimental
    Folate

    Participants will receive a 2 mg/ day dose of folate, for 12 weeks

    Drug: Folate

  • Placebo comparator
    Placebo

    Participants will receive a 2 mg/ day dose of placebo, for 12 weeks

    Drug: Placebo

Interventions

  • DrugFolate

    Folic acid taken as 2, 1mg capsule daily for 12 weeks

    Also known as: Folate or folic acid

  • DrugPlacebo

    Placebo taken as 2, 1mg capsule daily for 12 weeks

06

What researchers measure

Primary outcomes

  1. Correlation Between Baseline Blood Folate and Smoking Status

    Baseline blood folate lab levels are reported by smoking status.

    Time frame: Baseline

  2. Correlation Between Baseline Blood Folate and MTHFR Genotype

    Baseline blood folate lab levels are reported by MTHFR genotype.

    Time frame: Baseline

  3. Correlation Between Baseline Blood Folate Levels and Dietary Intake

    Baseline blood folate lab levels and dietary intake levels are reported.

    Time frame: Baseline

  4. 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.

    Time frame: Baseline score vs. week 12 score

  5. Correlation Between Baseline Serum B12 Levels and Smoking Status

    Baseline serum B12 lab levels are reported by smoking status.

    Time frame: Baseline

  6. Correlation Between Baseline Homocysteine Levels and Smoking Status

    Baseline blood homocysteine lab levels are reported by smoking status.

    Time frame: Baseline

  7. Correlation Between Baseline Blood B12 Levels and MTHFR Genotype

    Baseline blood B12 lab levels are reported by MTHFR genotype.

    Time frame: Baseline

  8. Correlation Between Baseline Blood Homocysteine Levels and MTHFR Genotype

    Baseline blood homocysteine lab levels are reported by MTHFR genotype.

    Time frame: Baseline

  9. Correlation Between Baseline Serum B12 Levels and Dietary Intake

    Baseline serum B12 lab levels and dietary intake levels are reported.

    Time frame: Baseline

  10. Correlation Between Baseline Blood Homocysteine Levels and Dietary Intake

    Baseline blood homocysteine lab levels and dietary intake levels are reported.

    Time frame: Baseline

  11. Correlation Between Baseline Blood Folate or B12 Levels and Dietary Intake

    Baseline blood folate and B12 lab levels and dietary intake levels are reported.

    Time frame: Baseline

Secondary outcomes

  1. 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.

    Time frame: Baseline

  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

    Baseline blood B12 lab levels are reported by deficit syndrome status.

    Time frame: Baseline

  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

    Baseline blood homocysteine lab levels are reported by deficit syndrome status.

    Time frame: Baseline

07

Results

Posted Aug 6, 2014

Participant flow

Forty six participants were enrolled; 38 completed screening and 32 received study drug.

Participant flow — Overall Study
MilestoneFolatePlacebo
Started1919
Initiated treatment1715
Completed1414
Not completed55
Withdrew: Lost to follow-up33
Withdrew: Withdrawal by subject22

Outcome measures

PrimaryCorrelation Between Baseline Blood Folate and Smoking Status

Baseline blood folate lab levels are reported by smoking status.

Time frame:
Baseline
Reported as:
Mean · nanograms per milliliter
Correlation Between Baseline Blood Folate and Smoking Status
nanograms per milliliterCurrent SmokerPast SmokerNever Smoker
Serum folate, ng/ml14.6 ± 3.314.6 ± 5.214.2 ± 4.1
RBC folate, ng/ml614 ± 142542 ± 122475 ± 161
PrimaryCorrelation Between Baseline Blood Folate and MTHFR Genotype

Baseline blood folate lab levels are reported by MTHFR genotype.

Time frame:
Baseline
Reported as:
Mean · nanograms/mL
Correlation Between Baseline Blood Folate and MTHFR Genotype
nanograms/mLCC GenotypeT- Genotype
Serum folate, ng/ml13.3 ± 3.315.2 ± 4.1
RBC folate, ng/ml624.8 ± 143.0542.8 ± 150.6
PrimaryCorrelation Between Baseline Blood Folate Levels and Dietary Intake

Baseline blood folate lab levels and dietary intake levels are reported.

Time frame:
Baseline
Reported as:
Mean · nanograms/mL
Correlation Between Baseline Blood Folate Levels and Dietary Intake
nanograms/mLOverall
Serum folate, ng/ml14.5 ± 3.9
RBC folate, ng/ml569.3 ± 148.1
PrimaryEfficacy 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.

Time frame:
Baseline score vs. week 12 score
Reported as:
Mean · Units on a scale
Efficacy of Folate Supplementation for Reducing Negative Symptoms as Measured by the SANS Modified Total
Units on a scaleFolatePlacebo
Efficacy of Folate Supplementation for Reducing Negative Symptoms as Measured by the SANS Modified Total-8.5 ± 7.6-9.7 ± 8.5
PrimaryCorrelation Between Baseline Serum B12 Levels and Smoking Status

Baseline serum B12 lab levels are reported by smoking status.

Time frame:
Baseline
Reported as:
Mean · picograms per milliliter
Correlation Between Baseline Serum B12 Levels and Smoking Status
picograms per milliliterCurrent SmokerPast SmokerNever Smoker
Correlation Between Baseline Serum B12 Levels and Smoking Status625 ± 273436 ± 130574 ± 160
PrimaryCorrelation Between Baseline Homocysteine Levels and Smoking Status

Baseline blood homocysteine lab levels are reported by smoking status.

Time frame:
Baseline
Reported as:
Mean · micromoles per liter
Correlation Between Baseline Homocysteine Levels and Smoking Status
micromoles per literCurrent SmokerPast SmokerNever Smoker
Correlation Between Baseline Homocysteine Levels and Smoking Status9.1 ± 2.610.8 ± 1.69 ± 2.5
PrimaryCorrelation Between Baseline Blood B12 Levels and MTHFR Genotype

Baseline blood B12 lab levels are reported by MTHFR genotype.

Time frame:
Baseline
Reported as:
Mean · picograms per milliliter
Correlation Between Baseline Blood B12 Levels and MTHFR Genotype
picograms per milliliterCC GenotypeT- Genotype
Correlation Between Baseline Blood B12 Levels and MTHFR Genotype605.5 ± 312.9557.1 ± 170.1
PrimaryCorrelation Between Baseline Blood Homocysteine Levels and MTHFR Genotype

Baseline blood homocysteine lab levels are reported by MTHFR genotype.

Time frame:
Baseline
Reported as:
Mean · micromoles/liter
Correlation Between Baseline Blood Homocysteine Levels and MTHFR Genotype
micromoles/literCC GenotypeT- Genotype
Correlation Between Baseline Blood Homocysteine Levels and MTHFR Genotype9.4 ± 2.99.6 ± 2.3
PrimaryCorrelation Between Baseline Serum B12 Levels and Dietary Intake

Baseline serum B12 lab levels and dietary intake levels are reported.

Time frame:
Baseline
Reported as:
Mean · picograms/mL
Correlation Between Baseline Serum B12 Levels and Dietary Intake
picograms/mLOverall
Correlation Between Baseline Serum B12 Levels and Dietary Intake566.6 ± 231.5
PrimaryCorrelation Between Baseline Blood Homocysteine Levels and Dietary Intake

Baseline blood homocysteine lab levels and dietary intake levels are reported.

Time frame:
Baseline
Reported as:
Mean · micromoles/liter
Correlation Between Baseline Blood Homocysteine Levels and Dietary Intake
micromoles/literOverall
Correlation Between Baseline Blood Homocysteine Levels and Dietary Intake9.6 ± 2.4
PrimaryCorrelation Between Baseline Blood Folate or B12 Levels and Dietary Intake

Baseline blood folate and B12 lab levels and dietary intake levels are reported.

Time frame:
Baseline
Reported as:
Mean · micrograms
Correlation Between Baseline Blood Folate or B12 Levels and Dietary Intake
microgramsOverall
Total folate, mcg531.3 ± 386.5
Dietary folate, mcg765.7 ± 637.7
Natural folate, mcg198.8 ± 73.3
Synthetic folate, mcg333.4 ± 362.9
Total B12, mcg7.5 ± 7.3
SecondaryCorrelations 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.

Time frame:
Baseline
Reported as:
Mean · nanograms/mL
Correlations Between Baseline Blood Folate and Clinical Ratings of Negative Symptoms by Comparing Lab Levels in Deficit Syndrome Versus Non-deficit Syndrome Patients
nanograms/mLDeficit SyndromeNot Deficit Syndrome
Serum folate, ng/ml14.9 ± 4.314.0 ± 3.5
RBC folate, ng/ml585 ± 171546 ± 123
SecondaryCorrelations 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.

Time frame:
Baseline
Reported as:
Mean · picograms/mL
Correlations Between Baseline Blood B12 Levels and Clinical Ratings of Negative Symptoms by Comparing Lab Levels in Deficit Syndrome Versus Non-deficit Syndrome Patients
picograms/mLDeficit SyndromeNot Deficit Syndrome
Correlations Between Baseline Blood B12 Levels and Clinical Ratings of Negative Symptoms by Comparing Lab Levels in Deficit Syndrome Versus Non-deficit Syndrome Patients603 ± 193513 ± 275
SecondaryCorrelations 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.

Time frame:
Baseline
Reported as:
Mean · micromoles/liter
Correlations Between Baseline Blood Homocysteine Levels and Clinical Ratings of Negative Symptoms by Comparing Lab Levels in Deficit Syndrome Versus Non-deficit Syndrome Patients
micromoles/literDeficit SyndromeNot Deficit Syndrome
Correlations Between Baseline Blood Homocysteine Levels and Clinical Ratings of Negative Symptoms by Comparing Lab Levels in Deficit Syndrome Versus Non-deficit Syndrome Patients9.4 ± 2.69.7 ± 2.5

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Folate—0/19 (0%)0/19 (0%)
Placebo—0/19 (0%)0/19 (0%)

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)PlaceboFolateTotal
<=18 years000
Between 18 and 65 years151732
>=65 years000
Age, Continuous
Age, Continuous(years)PlaceboFolateTotal
Mean46.5 ± 11.345.5 ± 9.646 ± 10.3
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboFolateTotal
Female246
Male131326
Region of Enrollment
Region of Enrollment(participants)PlaceboFolateTotal
United States151732
08

Study locations

1 site
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
09

References and documents

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. PubMed 21334854 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 5, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00249288
Lead sponsor
Massachusetts General Hospital
Collaborators
National Alliance for Research on Schizophrenia and Depression
Responsible party
Donald C. Goff, MD (Director of the Schizophrenia Clinical and Research Program, Massachusetts General Hospital) — Principal investigator
First posted
Nov 7, 2005
Start date
Dec 2003
Primary completion
Jun 2008
Completion
Jun 2008
Results posted
Aug 6, 2014
Last update
Apr 5, 2018

Study contacts

Donald C. Goff, M.D.
principal investigator · Massachusetts General Hospital

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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