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

Study Overview
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Brief Summary
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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).

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

Conditions
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Attention Deficit Hyperactivity Disorder (ADHD), Executive Function Deficits (EFD)

Intervention / Treatment
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* Drug: Placebo
* Drug: Memantine Hydrochloride
* Drug: OROS-Methylphenidate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female adults ages 18-50 years A diagnosis of childhood onset ADHD, according to the Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition (DSM-IV) based on clinical assessment A score of 20 or more on the Adult ADHD Investigator Symptom Report Scale (AISRS) EFDs as established by at least 2 abnormal (>65) subscales of BRIEF-A Exclusion Criteria: A history of non-response or intolerance to methylphenidate at adequate doses as determined by the clinician A history of non-response or intolerance to memantine at adequate doses as determined by the clinician Pregnant or nursing females 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 History of narrow angle glaucoma Current (within 3 months) DSM-IV criteria for substance abuse or dependence 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. Abnormal hematological or metabolic parameters IQ < 80 Current use of any psychotropic medication Lack of facility with the English language Investigator and his/her immediate family; defined as the investigator's spouse, parent, child, grandparent, or grandchild

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Subjects randomized to receive memantine-matched placebo in addition to open-label OROS-Methylphenidate | Drug: Placebo<br>* 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.<br>Drug: OROS-Methylphenidate<br>* 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.<br>* Other names: Concerta;|
| Active Comparator: Memantine<br>Subjects randomized to receive memantine in addition to open-label OROS-Methylphenidate | Drug: Memantine Hydrochloride<br>* 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.<br>* Other names: Namenda;Drug: OROS-Methylphenidate<br>* 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.<br>* Other names: Concerta;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADHD, Executive Function, Namenda, Concerta