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

Schizophrenia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01091506
• Other study ID #: D-003
• Status: Completed
• Phase: N/A
• First received: March 22, 2010
• Last updated: August 2, 2016
• Start date: March 2010
• Est. completion date: June 2014

Study information

• Verified date: January 2015
• Source: Pamlab, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: June 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 68 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Other:
• Placebo
Placebo once a day for 12 weeks
• L-methylfolate
L-methylfolate 15mg once a day for 12 weeks

Locations

Country	Name	City	State
United States	Massachusetts General Hospital (MGH) Schizophrenia Program at Freedom Trail Clinic	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Pamlab, Inc.	Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Examine the change in negative symptoms (SANS total score) after three months compared to placebo		Weeks 2, 8, and 12	No
Secondary	Examine the change in negative symptoms (SANS total score) in relation to change in plasma L-methylfolate levels		Weeks 2, 8, and 12	No
Secondary	Examine the change in MATRICS cognitive battery composite score after three months compared to placebo		Weeks 2, 8, and 12	No
Secondary	Examine the change in MATRICS cognitive battery composite score after three months in relation to change in plasma L-methylfolate concentration.		Weeks 2, 8, and 12	No
Secondary	Examine the change in psychotic symptoms as measured by the PANSS total and subscale scores after three months compared to placebo		Weeks 2, 8, and 12	No
Secondary	Examine the change in psychotic symptoms (PANSS score) in relation to change in plasma L-methylfolate concentration.		Weeks 2, 8, and 12	No
Secondary	Examine the change in plasma homocysteine and methionine concentrations following a three-month trial of L-methylfolate 15 mg/d compared to placebo.		Weeks 2, 8, and 12	No