L-methylfolate Supplementation to OROS-Methylphenidate Pharmacotherapy in ADHD Adults

L-methylfolate Supplementation to OROS-Methylphenidate Pharmacotherapy in ADHD Adults: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial

This pilot study seeks to evaluate initial evidence for the effect of L-methylfolate supplementation to OROS-Methylphenidate pharmacotherapy on ADHD symptoms and associated features in adults with ADHD, as well as tolerability of this supplementation. The investigators will conduct a 12-week double-blind randomized placebo-controlled trial with L-methylfolate supplementing open-label OROS-Methylphenidate (OROS-MPH). The investigators propose to examine 40 adult (ages 18-55) subjects satisfying the DSM-IV diagnostic criteria for ADHD.

Study Overview

• Status: Completed
• Conditions: Attention Deficit Hyperactivity Disorder
• Intervention / Treatment: Drug: L-methylfolate; Drug: OROS-Methylphenidate; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female adults ages 18-55 years of age.
2. A diagnosis of childhood onset ADHD, meeting all but the age of onset criteria according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), based on clinical assessment. Childhood onset will be defined according to established research criteria, requiring onset of two symptoms of inattentive or of impulsive/hyperactive traits by the age of 12.
3. A score of 24 or more on the Adult ADHD Investigator Symptom Report Scale (AISRS).

Exclusion Criteria:

1. A history of non-response or intolerance to methylphenidate at adequate doses as determined by the clinician.
2. A history of intolerance to L-methylfolate supplementation.
3. Pregnant or nursing females.
4. Serious, unstable medical illness including hepatic, renal, gastroenterological, respiratory, cardiovascular, endocrinologic (thyroid), neurologic (seizure), immunologic, or hematologic disease.
5. Glaucoma.
6. Clinically unstable psychiatric conditions including suicidality, homicidality, bipolar disorder, psychosis, history of or current marked anxiety, tension or agitation potentially exacerbated by a stimulant, or lifetime history of any other clinically serious condition potentially exacerbated by a stimulant, such as mania or psychosis.
7. Significant impairment due to tics, based on clinician judgment.
8. A family history or diagnosis of Tourette's syndrome
9. Current (within 3 months) DSM-IV criteria for abuse or dependence with any psychoactive substance other than nicotine.
10. Multiple adverse drug reactions.
11. Any other concomitant medication considered to be effective for management of ADHD; individuals on stable treatment with agents with central nervous system activity will be allowed to participate, as detailed in the Concomitant Medication portion of the protocol.
12. Current use of MAO Inhibitor or use within the past two weeks.
13. Investigator and his/her immediate family; defined as the investigator's spouse, parent, child, grandparent, or grandchild.
14. Use of supplemental folic acid greater than 400 mcg per day, L-methylfolate, or Omega-3 Fatty Acids greater than 800 mg per day within two weeks prior to the baseline study visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: L-Methylfolate; 15 mg of L-Methylfolate (Deplin®) daily for 12 weeks as a supplement to OROS-Methylphenidate.	Drug: L-methylfolate; 15mg/day L-methylfolate.; Other Names: Deplin®; Drug: OROS-Methylphenidate; All subjects will be treated with open-label OROS-MPH; Other Names: Concerta®
Placebo Comparator: Placebo; 15 mg matched placebo comparator, with open-label OROS-Methylphenidate	Drug: OROS-Methylphenidate; All subjects will be treated with open-label OROS-MPH; Other Names: Concerta®; Drug: Placebo; 15 mg matched placebo comparator, with open-label OROS-Methylphenidate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adult ADHD Investigator Symptom Rating Scale (AISRS)	The AISRS is an 18-item questionnaire administered by the clinician assessing each of the individual DSM-IV symptoms of ADHD. Each symptom is rated on a scale of severity from 0 (none) to 3 (severe), and the 18 symptom questions are summed to calculate a total score. The minimum total score is a 0, while the maximum total score is a 54. The AISRS was compared from baseline to completion, over the course of the 12 week study.	12 weeks

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Pamlab, Inc.
• Investigators: Principal Investigator: Craig Surman, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: May 10, 2013
• First Submitted That Met QC Criteria: May 13, 2013
• First Posted (Estimate): May 14, 2013

Study Record Updates

• Last Update Posted (Actual): November 14, 2017
• Last Update Submitted That Met QC Criteria: October 17, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: ADHD; Attention Deficit Hyperactivity Disorder; L-methylfolate; Deplin; Medical Food; Natural Treatments
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Hyperkinesis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Methylphenidate
• Other Study ID Numbers: 2012-P-000379