Trial Outcomes & Findings for Memantine for Executive Dysfunction in Adults With ADHD: A Pilot Study (NCT NCT01533493)

Last Updated: 2014-04-08

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

33 participants

Primary outcome timeframe

baseline, 12 weeks

Results posted on

2014-04-08

Participant Flow

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)

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	12	14
Overall Study COMPLETED	7	11
Overall Study NOT COMPLETED	5	3

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Adverse Event	2	1
Overall Study Withdrawal by Subject	1	2
Overall Study Lost to Follow-up	2	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Memantine n=12 Participants 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.	Placebo n=14 Participants 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.	Total n=26 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	34.25 years STANDARD_DEVIATION 9.77 • n=5 Participants	38.43 years STANDARD_DEVIATION 10.57 • n=7 Participants	36.5 years STANDARD_DEVIATION 10.23 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants	14 participants n=7 Participants	26 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline, 12 weeks

Outcome measures

Outcome measures
Measure	Memantine n=12 Participants 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.	Placebo n=14 Participants 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.
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	-21 percentage change from baseline score Standard Deviation 0.132

Adverse Events

Memantine

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Joseph Biederman

Massachusetts General Hospital

Phone: 617-724-1743

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Memantine n=12 participants at risk 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.	Placebo n=14 participants at risk 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.
Psychiatric disorders Anxiety	16.7% 2/12 • Number of events 4 • Adverse events were collected weekly, up to 12 weeks.	14.3% 2/14 • Number of events 2 • Adverse events were collected weekly, up to 12 weeks.
Metabolism and nutrition disorders Appetite Decrease	41.7% 5/12 • Number of events 10 • Adverse events were collected weekly, up to 12 weeks.	66.7% 8/12 • Number of events 18 • Adverse events were collected weekly, up to 12 weeks.
Cardiac disorders Chest discomfort	0.00% 0/12 • Adverse events were collected weekly, up to 12 weeks.	14.3% 2/14 • Number of events 2 • Adverse events were collected weekly, up to 12 weeks.
General disorders Dizziness	16.7% 2/12 • Number of events 3 • Adverse events were collected weekly, up to 12 weeks.	0.00% 0/14 • Adverse events were collected weekly, up to 12 weeks.
General disorders Dry Mouth	50.0% 6/12 • Number of events 19 • Adverse events were collected weekly, up to 12 weeks.	42.9% 6/14 • Number of events 8 • Adverse events were collected weekly, up to 12 weeks.
General disorders Fatigue	33.3% 4/12 • Number of events 6 • Adverse events were collected weekly, up to 12 weeks.	21.4% 3/14 • Number of events 10 • Adverse events were collected weekly, up to 12 weeks.
Psychiatric disorders Forgetting	8.3% 1/12 • Number of events 1 • Adverse events were collected weekly, up to 12 weeks.	14.3% 2/14 • Number of events 2 • Adverse events were collected weekly, up to 12 weeks.
General disorders Head discomfort	8.3% 1/12 • Number of events 2 • Adverse events were collected weekly, up to 12 weeks.	21.4% 3/14 • Number of events 5 • Adverse events were collected weekly, up to 12 weeks.
General disorders Headache	50.0% 6/12 • Number of events 9 • Adverse events were collected weekly, up to 12 weeks.	14.3% 2/14 • Number of events 2 • Adverse events were collected weekly, up to 12 weeks.
Cardiac disorders Heart Palpitations	33.3% 4/12 • Number of events 9 • Adverse events were collected weekly, up to 12 weeks.	28.6% 4/14 • Number of events 12 • Adverse events were collected weekly, up to 12 weeks.
General disorders Increased Intoxication	16.7% 2/12 • Number of events 2 • Adverse events were collected weekly, up to 12 weeks.	0.00% 0/14 • Adverse events were collected weekly, up to 12 weeks.
General disorders Insomnia	25.0% 3/12 • Number of events 4 • Adverse events were collected weekly, up to 12 weeks.	42.9% 6/14 • Number of events 7 • Adverse events were collected weekly, up to 12 weeks.
Psychiatric disorders Irritable	16.7% 2/12 • Number of events 3 • Adverse events were collected weekly, up to 12 weeks.	14.3% 2/14 • Number of events 3 • Adverse events were collected weekly, up to 12 weeks.
Musculoskeletal and connective tissue disorders Jittery	16.7% 2/12 • Number of events 2 • Adverse events were collected weekly, up to 12 weeks.	28.6% 4/14 • Number of events 7 • Adverse events were collected weekly, up to 12 weeks.
Gastrointestinal disorders Nausea	16.7% 2/12 • Number of events 4 • Adverse events were collected weekly, up to 12 weeks.	7.1% 1/14 • Number of events 4 • Adverse events were collected weekly, up to 12 weeks.
Psychiatric disorders Perceptual Change	16.7% 2/12 • Number of events 2 • Adverse events were collected weekly, up to 12 weeks.	0.00% 0/14 • Adverse events were collected weekly, up to 12 weeks.
General disorders Sweaty Palms	16.7% 2/12 • Number of events 7 • Adverse events were collected weekly, up to 12 weeks.	0.00% 0/14 • Adverse events were collected weekly, up to 12 weeks.