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

NCT01091506 | Completed

• 1 other identifier: D-003
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Schizophrenia

Keywords

L-methylfolate; Deplin; schizophrenia; folate; folic acid; homocysteine; methionine; MTHFR genotype; C677T mutation; vitamin B6; vitamin B12; psychotic symptoms; MTHFR C677T Polymorphism

Outcome Measures

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.

  Weeks 2, 8, and 12

Secondary Outcomes (9)

• 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.

  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

  Weeks 2, 8, and 12

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

  Weeks 2, 8, and 12

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

  Weeks 2, 8, and 12

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

  Weeks 2, 8, and 12

Study Arms (2)

L-methylfolate

EXPERIMENTAL

L-methylfolate 15mg (a medical food)

Other: L-methylfolate

Placebo

PLACEBO COMPARATOR

Placebo

Other: Placebo

Interventions

Placebo OTHER

Placebo once a day for 12 weeks

Placebo

L-methylfolate OTHER

L-methylfolate 15mg once a day for 12 weeks

Also known as: Deplin

L-methylfolate

Eligibility Criteria

• Age: 18 Years - 68 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 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

Sponsors & Collaborators

• Pamlab, Inc.: lead
• Massachusetts General Hospital: collaborator

Study Sites (1)

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

Boston, Massachusetts, United States

Location

Related Publications (1)

• Roffman JL, Petruzzi LJ, Tanner AS, Brown HE, Eryilmaz H, Ho NF, Giegold M, Silverstein NJ, Bottiglieri T, Manoach DS, Smoller JW, Henderson DC, Goff DC. Biochemical, physiological and clinical effects of l-methylfolate in schizophrenia: a randomized controlled trial. Mol Psychiatry. 2018 Feb;23(2):316-322. doi: 10.1038/mp.2017.41. Epub 2017 Mar 14.

  PMID: 28289280 DERIVED

MeSH Terms

Conditions

Schizophrenia

Interventions

5-methyltetrahydrofolate

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Officials

• Joshua Roffman, MD

  Massachusetts General Hospital Schizophrenia Program at Freedom Trail Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2010
• First Posted: March 24, 2010
• Study Start: March 1, 2010
• Primary Completion: March 1, 2014
• Study Completion: June 1, 2014
• Last Updated: August 3, 2016

Record last verified: 2015-01

Locations

US (1)