Memantine for Executive Dysfunction in Adults With ADHD: A Pilot Study

This is a 12-week clinical trial evaluating the efficacy and safety of memantine hydrochloride (Namenda) in the treatment of executive function deficits (EFDs) in adults with Attention Deficit Hyperactivity Disorder (ADHD) receiving open-label treatment with OROS-Methylphenidate (OROS-MPH, Concerta). The study aims to examine the effects of treatment with memantine on ADHD symptoms. Following screening procedures, memantine is prescribed in randomized, double-blind fashion (equal chance of medication or placebo) for 12 weeks, along with open-label OROS-MPH (everyone receives medication).

Study Overview

• Status: Completed
• Conditions: Attention Deficit Hyperactivity Disorder (ADHD); Executive Function Deficits (EFD)
• Intervention / Treatment: Drug: Placebo; Drug: OROS-Methylphenidate; Drug: Memantine Hydrochloride

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female adults ages 18-50 years
2. A diagnosis of childhood onset ADHD, according to the Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition (DSM-IV) based on clinical assessment
3. A score of 20 or more on the Adult ADHD Investigator Symptom Report Scale (AISRS)
4. EFDs as established by at least 2 abnormal (>65) subscales of BRIEF-A

Exclusion Criteria:

1. A history of non-response or intolerance to methylphenidate at adequate doses as determined by the clinician
2. A history of non-response or intolerance to memantine at adequate doses as determined by the clinician
3. Pregnant or nursing females
4. A history of clinically unstable or significant other psychiatric conditions including suicidality, homicidality, bipolar disorder, psychosis, or current tic disorder, as judged by the clinician
5. History of narrow angle glaucoma
6. Current (within 3 months) DSM-IV criteria for substance abuse or dependence
7. Medical condition or treatment that will either jeopardize subject safety or affect the scientific merit of the study, including cardiovascular disease, hypertension, history of renal or hepatic impairment, organic brain disorders, or history of seizure disorder.
8. Abnormal hematological or metabolic parameters
9. IQ < 80
10. Current use of any psychotropic medication
11. Lack of facility with the English language
12. Investigator and his/her immediate family; defined as the investigator's spouse, parent, child, grandparent, or grandchild

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
Placebo Comparator: Placebo; Subjects randomized to receive memantine-matched placebo in addition to open-label OROS-Methylphenidate	Drug: Placebo; Memantine-matched placebo will be prescribed following approved FDA dosing guidelines for Alzheimer's dementia, beginning at 5mg in AM and increasing in BID doses by 5mg weekly to a maximum dose of 10mg BID.; Drug: OROS-Methylphenidate; OROS-Methylphenidate will be openly prescribed, starting with an initial dose of 36mg/day and titrated to optimal response to a maximum daily dose of 1.3mg/kg or 108mg/day, whichever is lower, according to clinician judgment. During titration, dose will be increased on a weekly basis in 36mg/day increments. The dose may be reduced by 18 or 36mg/day increments if adverse effects occur or if the subject discontinues treatment.; Other Names: Concerta; OROS-MPH
Active Comparator: Memantine; Subjects randomized to receive memantine in addition to open-label OROS-Methylphenidate	Drug: OROS-Methylphenidate; OROS-Methylphenidate will be openly prescribed, starting with an initial dose of 36mg/day and titrated to optimal response to a maximum daily dose of 1.3mg/kg or 108mg/day, whichever is lower, according to clinician judgment. During titration, dose will be increased on a weekly basis in 36mg/day increments. The dose may be reduced by 18 or 36mg/day increments if adverse effects occur or if the subject discontinues treatment.; Other Names: Concerta; OROS-MPH; Drug: Memantine Hydrochloride; Memantine will be prescribed following approved FDA dosing guidelines for Alzheimer's dementia, beginning at 5mg in AM and increasing in BID doses by 5mg weekly to a maximum dose of 10mg BID.; Other Names: Namenda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Global Executive Composite T-Score on the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A)	This is a 75-item checklist with a large normative sample, internal consistency, test-retest reliability, inter-rater reliability, and external and concurrent validity, divided into nine empirically and theoretically derived and T-scored subscales: Inhibit, Shift, Emotional Control, Self-Monitor, Initiate, Working Memory, Plan/Organize, Task Monitor, and Organization of Materials. Example item: "I make careless errors when completing tasks." Items are rated 1 "Never," 2 "Sometimes," or 3 "Often." The Global Executive Composite (GEC) Score is calculated by totaling all items on the scale. GEC T-scores range from 34-108, with higher scores indicating more difficulties with executive function.	baseline, 12 weeks

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: The American Professional Society of ADHD and Related Disorders (APSARD)

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: February 8, 2012
• First Submitted That Met QC Criteria: February 10, 2012
• First Posted (Estimate): February 15, 2012

Study Record Updates

• Last Update Posted (Estimate): April 8, 2014
• Last Update Submitted That Met QC Criteria: March 10, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: ADHD; Concerta; Executive Function; Namenda
• Additional Relevant MeSH Terms: Mental Disorders; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Antiparkinson Agents; Anti-Dyskinesia Agents; Methylphenidate; Memantine
• Other Study ID Numbers: 2012P000301