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

August 2, 2016 updated by: Pamlab, Inc.
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

55

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States
        • Massachusetts General Hospital (MGH) Schizophrenia Program at Freedom Trail Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Other: Placebo
Placebo once a day for 12 weeks
Experimental: L-methylfolate
L-methylfolate 15mg (a medical food)
Other: L-methylfolate
L-methylfolate 15mg once a day for 12 weeks
Other Names:
  • Deplin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Weeks 2, 8, and 12

Secondary Outcome Measures

Outcome Measure
Time Frame
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
Week 12
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
Weeks 2, 8, and 12
Examine the change in negative symptoms (SANS total score) after three months compared to placebo
Time Frame: Weeks 2, 8, and 12
Weeks 2, 8, and 12
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
Weeks 2, 8, and 12
Examine the change in MATRICS cognitive battery composite score after three months compared to placebo
Time Frame: Weeks 2, 8, and 12
Weeks 2, 8, and 12
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
Weeks 2, 8, and 12
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
Weeks 2, 8, and 12
Examine the change in psychotic symptoms (PANSS score) in relation to change in plasma L-methylfolate concentration.
Time Frame: Weeks 2, 8, and 12
Weeks 2, 8, and 12
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
Weeks 2, 8, and 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pamlab, Inc.

Collaborators

Massachusetts General Hospital

Investigators

  • Principal Investigator: Joshua Roffman, MD, Massachusetts General Hospital Schizophrenia Program at Freedom Trail Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2010

Primary Completion (Actual)

March 1, 2014

Study Completion (Actual)

June 1, 2014

Study Registration Dates

First Submitted

March 22, 2010

First Submitted That Met QC Criteria

March 23, 2010

First Posted (Estimate)

March 24, 2010

Study Record Updates

Last Update Posted (Estimate)

August 3, 2016

Last Update Submitted That Met QC Criteria

August 2, 2016

Last Verified

January 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D-003

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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