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

Sponsor:	Pamlab, L.L.C.
Collaborator:	Massachusetts General Hospital
Information provided by (Responsible Party):	Pamlab, L.L.C.
ClinicalTrials.gov Identifier:	NCT01091506

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:

Genetics Home Reference related topics: Help Me Understand Genetics

MedlinePlus related topics: Mental Disorders Psychotic Disorders Schizophrenia

U.S. FDA Resources

Further study details as provided by Pamlab, L.L.C.:

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, L.L.C.

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, L.L.C.
ClinicalTrials.gov Identifier:	NCT01091506 History of Changes
Other Study ID Numbers:	D-003
Study First Received:	March 22, 2010
Last Updated:	April 18, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by Pamlab, L.L.C.:

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 23, 2012