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

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: schizophrenia

MedlinePlus related topics: Schizophrenia

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 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 ] [ 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 total and subscale scores 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 ]


Enrollment:	55
Study Start Date:	March 2010
Study Completion Date:	June 2014
Primary Completion Date:	March 2014 (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 (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations


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

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


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:	August 2, 2016
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 Spectrum and Other Psychotic Disorders Mental Disorders Tetrahydrofolates Vitamin B Complex	Vitamins Micronutrients Growth Substances Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 30, 2016