An Exploratory, Randomized, Blinded, Placebo-Controlled Trial of Folic Acid and L-methylfolate in Parkinson's Disease

This study is being conducted to assess the impact of folate and L-methylfolate on the progression of Parkinson's. The investigators are specifically looking for the effect of these nutritional supplements in Parkinson's patients who have an antibody that effects their body's utilization of folate. An antibody is a protein produced by the body's immune system to recognize foreign substances. Normally, people do not have an antibody that prevents folate from working properly in the brain but it appears that some people may have such an antibody. Folate is an important vitamin that takes part in many critical cell functions so an antibody that prevented it from entering the brain properly could cause or worsen certain neurological disorders like Parkinson's. The results of this preliminary study will help determine whether it is reasonable to proceed with further study of any of these supplements for the treatment of Parkinson's. Patients interested in participating will have a blood test to see if they have folate antibodies. Patients with the antibody will be eligible to further participate in the study. The investigators will measure the effects of folate and L-methylfolate on Parkinson's disease by measuring the change in your Parkinson's disease symptoms over three months of treatment. The investigators will also be looking at the blood of some individuals who do not have Parkinson's. This is called a control group and will allow us to compare how common the folate antibody is in the general population compared with the Parkinson's population.

Study Overview

• Status: Terminated
• Conditions: Parkinson's Disease
• Intervention / Treatment: Dietary supplement: Folic Acid, Vitamin B6, Vitamin B12; Dietary supplement: B6, B12, L-methylfolate; Dietary supplement: B6, B12, Placebo

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • Manhasset, New York, United States, 11030
      • The Feinstein Institute For Medical Recearch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• PD subjects:

  • Diagnosis of Parkinson's based upon the presence of 2 or more of the cardinal clinical features of the disease as determined by a movement disorders specialist.
  • Age > 30.
  • Able to provide informed consent.
  • All anti-Parkinson's medications will be permitted but all evaluations will be done in the medication OFF state (at least 12 hours following the last dose of medication).
• Healthy Controls *Age > 30

Exclusion Criteria:

• PD Subjects:

  • Age < 30.
  • Presence of concomitant active neurological disorders as deemed significant by the investigator.
  • History of clinically significant diabetes, vascular disease, renal, thyroid or hepatic dysfunction or of Leber's optic neuropathy as determined by the investigator.
  • History of significant medical illness as determined by the investigators.
  • The following medications will be excluded: thiazide diuretics, azathioprine, phenytoin, phenobarbital, primidone, sulfa-containing medications, cimetidine, anti-tuberculosis medications, methotrexate, chemotherapeutic agents and oral contraceptives.
  • Subjects taking vitamin supplementation in excess of one daily standard multivitamin.
  • Pregnancy (excluded not for perceived risk but because most pregnant women are taking supplemental folate).

• Healthy Controls:

  • Age < 30
  • Any known active neurological condition deemed significant by the investigator.
  • History of significant, active renal or hepatic dysfunction as determined by the investigator.
  • History of significant active medical illness as determined by the investigators.
  • The following medications will be excluded: thiazide diuretics, azathioprine, phenytoin, phenobarbital, primidone, sulfa-containing medications, cimetidine, anti-tuberculosis medications, methotrexate, chemotherapeutic agents and oral contraceptives.
  • Subjects taking vitamin supplementation in excess of one standard daily multivitamin.
  • Pregnancy (most pregnant women are taking folate).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1. B6, B12, folate; Triple therapy with folate. Intervention #1.	Dietary supplement: Folic Acid, Vitamin B6, Vitamin B12; Intervention #1. A combination of the following vitamin supplements: 2.5mg of folate, 25mg of vitamin B6 and 2mg of vitamin B12. This combination will be described as "triple therapy with folate."
Active Comparator: Arm 2. B6, B12, L-methylfolate; Triple therapy with L-methylfolate. Intervention #2	Dietary supplement: B6, B12, L-methylfolate; Intervention #2. A combination of the following vitamin supplements: 2.8mg of L-methylfolate, 25 mg of vitamin B6 and 2mg of vitamin B12.
Placebo Comparator: Arm 3. B6, B12, Placebo; Triple therapy with placebo. Intervention #3.	Dietary supplement: B6, B12, Placebo; Intervention #3. A combination of the following vitamin supplements: 25mg of vitamin B6 and 2mg of vitamin B12 without supplementary folate or L-methylfolate. This combination will be described as "triple therapy with placebo"

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
This study is being conducted to assess the impact of folate and L-methylfolate on the progression of Parkinson's. The primary endpoint variable will be the change in UPDRS from baseline to 3 months ("change score").	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Secondary endpoints will be Folate receptor autoantibody levels and plasma Hcy levels	3 years

Collaborators and Investigators

• Sponsor: Northwell Health
• Investigators: Principal Investigator: Michael Pourfar, MD, Northwell Health

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: February 26, 2009
• First Submitted That Met QC Criteria: February 27, 2009
• First Posted (Estimate): March 2, 2009

Study Record Updates

• Last Update Posted (Estimate): May 15, 2015
• Last Update Submitted That Met QC Criteria: May 13, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Micronutrients; Hematinics; Vitamins; Folic Acid; Vitamin B 12; Hydroxocobalamin; Vitamin B Complex; Vitamin B 6; Pyridoxal; Pyridoxine
• Other Study ID Numbers: GCRC 0143

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No