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

This study is currently recruiting participants.
Verified December 2012 by Pamlab, Inc.
Sponsor:
Collaborator:
Massachusetts General Hospital
Information provided by (Responsible Party):
Pamlab, Inc.
ClinicalTrials.gov Identifier:
NCT01091506
First received: March 22, 2010
Last updated: December 3, 2012
Last verified: December 2012
History of Changes
  Purpose

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.


Condition Intervention
Schizophrenia
 Other: Placebo
Other: L-methylfolate

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: A Placebo-Controlled Study of Physiologic Effects of L-methylfolate in Schizophrenia Patients

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Pamlab, Inc.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Examine the change in DLPFC activation in patients receiving L-methylfolate 15 mg/d versus placebo as measured by fMRI using Sternberg's Iterm Recognition Paradigm. [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Examine the change in negative symptoms (SANS total score) after three months compared to placebo [ Time Frame: Weeks 2, 8, and 12 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Examine the change in MATRICS cognitive battery composite score after three months compared to placebo [ Time Frame: Weeks 2, 8, and 12 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Examine the change in psychotic symptoms as measured by the PANSS psychosis subscale score after three months compared to placebo [ Time Frame: Weeks 2, 8, and 12 ] [ Designated as safety issue: No ]
  • Examine the change in psychotic symptoms (PANSS score) in relation to change in plasma L-methylfolate concentration. [ Time Frame: Weeks 2, 8, and 12 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: March 2010
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: L-methylfolate
L-methylfolate 15mg (a medical food)
 Other: L-methylfolate
L-methylfolate 15mg once a day for 12 weeks
Other Name: Deplin
Placebo Comparator: Placebo
Placebo
 Other: Placebo
Placebo once a day for 12 weeks

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.

  Eligibility

Ages Eligible for Study:   18 Years to 68 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01091506

Contacts
Contact: Lori W Barrentine, MS, PA-C 985-867-5787 lbarrentine@pamlab.com
Contact: Page A Young, BS 985-867-5788 pyoung@pamlab.com

Locations
United States, Massachusetts
Massachusetts General Hospital (MGH) Schizophrenia Program at Freedom Trail Clinic Recruiting
Boston, Massachusetts, United States
Contact: Joshua Roffman, MD     617-912-7882     JROFFMAN@PARTNERS.ORG    
Principal Investigator: Joshua Roffman, MD            
Sponsors and Collaborators
Pamlab, Inc.
Massachusetts General Hospital
Investigators
Principal Investigator: Joshua Roffman, MD Massachusetts General Hospital Schizophrenia Program at Freedom Trail Clinic
  More Information

No publications provided

Responsible Party: Pamlab, Inc.
ClinicalTrials.gov Identifier: NCT01091506     History of Changes
Other Study ID Numbers: D-003
Study First Received: March 22, 2010
Last Updated: December 3, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Pamlab, Inc.:
L-methylfolate
Deplin
schizophrenia
folate
folic acid
homocysteine
methionine
 MTHFR genotype
C677T mutation
vitamin B6
vitamin B12
psychotic symptoms
MTHFR C677T Polymorphism

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders

ClinicalTrials.gov processed this record on May 16, 2013