Attention Deficit Hyperactivity Disorder (ADHD), Executive Function Deficits (EFD)
Conditions
Keywords
ADHD, Executive Function, Namenda, Concerta
Brief summary
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).
Interventions
DRUGPlacebo
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.
DRUGMemantine 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.
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.
Sponsors
The American Professional Society of ADHD and Related Disorders (APSARD)
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Global Executive Composite T-Score on the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) | baseline, 12 weeks | 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. |
Countries
United States
Participant flow
Pre-assignment details
Of the 33 participants enrolled, 26 were randomized to receive the treatment. The remaining 7 participants were either lost to follow-up after signing consent (n=3) or withdrew consent before being randomized (n=4)
Participants by arm
| Arm | Count |
|---|---|
| Memantine Subjects randomized to receive Memantine in addition to open-label OROS-Methylphenidate
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.
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. | 12 |
| Placebo Subjects randomized to receive memantine-matched placebo in addition to open-label OROS-Methylphenidate
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.
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. | 14 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo | Memantine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 12 Participants | 26 Participants |
| Age, Continuous | 38.43 years STANDARD_DEVIATION 10.57 | 34.25 years STANDARD_DEVIATION 9.77 | 36.5 years STANDARD_DEVIATION 10.23 |
| Region of Enrollment United States | 14 participants | 12 participants | 26 participants |
| Sex: Female, Male Female | 7 Participants | 7 Participants | 14 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 12 | 13 / 14 |
| serious Total, serious adverse events | 0 / 12 | 0 / 14 |
Outcome results
Primary
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.
Time frame: baseline, 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Memantine | Percent Change in Global Executive Composite T-Score on the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) | -24 percentage change from baseline score | Standard Deviation 0.169 |
| Placebo | Percent Change in Global Executive Composite T-Score on the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) | -21 percentage change from baseline score | Standard Deviation 0.132 |