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Completed

NCT Number: NCT01091506

A Placebo-Controlled Study of Physiologic Effects of L-methylfolate in Schizophrenia Patients

This study is a 12-week, double-blind, placebo-controlled trial of L-methylfolate 15 mg/d supplementation in schizophrenia patients with mild or greater negative symptoms. L-methylfolate, a prescription medical food, is the activated form of folate required for conversion of homocysteine to methionine and hence is the optimal form of folate for supplementation, since it eliminates the need for activation by MTHFR. The purpose of this study is to examine the change in plasma L-methylfolate concentrations following a three-month trial of L-methylfolate 15 mg/d compared to placebo.

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Key information

Conditions

Schizophrenia Mental Disorders Schizophrenia Spectrum and Other Psychotic Disorders

Age range

18 year–68 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Massachusetts General Hospital (MGH) Schizophrenia Program at Freedom Trail Clinic

Boston, Massachusetts, United States

About this study

Blood levels of L-methylfolate and biological activity will be evaluated by examining changes in plasma homocysteine concentrations, serum methionine concentrations and changes in brain activation as measured by fMRI.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Diagnosis of schizophrenia, any subtype
  • Male of female
  • Age 18-68 years
  • Treated with an antipsychotic for at least 6 months at a stable dose for at least 6 weeks
  • PANSS total score of at least 60, with at least 3 (moderate) on one negative symptom item or on one positive symptom item
  • Simpson Angus Scale (SAS) for the EPS total score of 12 or less and
  • A score of 2 (mild) or less on all items of the Calgary Depression Rating Scale (CDRS)
  • Comprehension of English adequate to complete cognitive testing

Exclusion criteria

  • Unable to provide informed consent
  • CBC results consistent with megaloblastic anemia
  • Serum creatinine concentration greater than 1.4
  • Current use of folate supplementation > 400mcg folate
  • Alcohol or other substance abuse within 3 months (nicotine allowed)
  • Current use of any of the following medications: phenobarbital, phenytoin, carbamazepine, valproic acid, fosphenytoin, primidone or pyrimethamine
  • Positive baseline urine toxic screen, (positive test for PCP, barbiturates, cannabinoids, amphetamines, benzodiazepines, opiates, or cocaine)
  • Unstable medical illness (exclusionary lab values are listed in Appendix A)
  • Unstable psychiatric illness
  • Seizure disorder
  • Pregnant or nursing, or planning/trying to get pregnant within the next 6 months, and
  • DSM-IV diagnosis of major depressive disorder

Treatment and study plan

Placebo

Other

Placebo once a day for 12 weeks

L-methylfolate

Other

L-methylfolate 15mg once a day for 12 weeks

Other names: Deplin

Primary outcomes

  1. Examine the change in plasma L-methylfolate concentrations following a three-month trial of L-methylfolate 15 mg/d compared to placebo.

    Time frame: Weeks 2, 8, and 12

Secondary outcomes

  1. Examine the change in brain activation in patients receiving L-methylfolate 15 mg/d versus placebo as measured by fMRI using Sternberg's Iterm Recognition Paradigm, as well as changes in cortical thickness and connectivity.

    Time frame: Week 12

  2. Examine the relationship between MTHFR genotype, change in plasma homocysteine, and methionine concentration, and change in DLPC activation in subjects receiving L-methylfolate

    Time frame: Weeks 2, 8, and 12

  3. Examine the change in negative symptoms (SANS total score) after three months compared to placebo

    Time frame: Weeks 2, 8, and 12

  4. Examine the change in negative symptoms (SANS total score) in relation to change in plasma L-methylfolate levels

    Time frame: Weeks 2, 8, and 12

  5. Examine the change in MATRICS cognitive battery composite score after three months compared to placebo

    Time frame: Weeks 2, 8, and 12

  6. Examine the change in MATRICS cognitive battery composite score after three months in relation to change in plasma L-methylfolate concentration.

    Time frame: Weeks 2, 8, and 12

  7. Examine the change in psychotic symptoms as measured by the PANSS total and subscale scores after three months compared to placebo

    Time frame: Weeks 2, 8, and 12

  8. Examine the change in psychotic symptoms (PANSS score) in relation to change in plasma L-methylfolate concentration.

    Time frame: Weeks 2, 8, and 12

  9. Examine the change in plasma homocysteine and methionine concentrations following a three-month trial of L-methylfolate 15 mg/d compared to placebo.

    Time frame: Weeks 2, 8, and 12

Sponsors and collaborators

Lead sponsor

Pamlab, Inc.

Industry

Collaborators

  • Massachusetts General Hospital

Registry information

Important dates

Study start
2010
Primary completion
2014
Study completion
2014
First posted
Mar 24, 2010
Registry last updated
Aug 3, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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