Trial Outcomes & Findings for Down Syndrome Memantine Follow-up Study (NCT NCT02304302)

NCT ID: NCT02304302

Last Updated: 2023-06-27

Results Overview

The primary efficacy measure is focused on episodic memory. The CVLT-II short form assesses supraspan word learning ability as an index of episodic verbal long-term memory. We hypothesize that treatment with memantine will produce significant improvements in this test. The main dependent variable selected, based on prior literature was the total number of target items correct summed across learning trials 1-4. The values for this measure have been recorded as change in score from baseline (T1) to after the treatment (T2). Scale Range: from 0 to 36; higher scores represent better outcomes.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 160 participants
• Primary outcome timeframe: baseline and 16 weeks from start of treatment
• Results posted on: 2023-06-27

Participant Flow

Participant milestones

Measure	Memantine Memantine capsules were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Memantine: Encapsulated Memantine 10 mg bid (after four-week standard dose titration protocol)	Placebo Identically-looking placebo capsules to memantine were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Placebo: Identically looking placebo capsules bid (after a four-week regimen designed to mimic standard dose titration protocol)
Overall Study STARTED	81	79
Overall Study COMPLETED	73	76
Overall Study NOT COMPLETED	8	3

Reasons for withdrawal

Measure	Memantine Memantine capsules were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Memantine: Encapsulated Memantine 10 mg bid (after four-week standard dose titration protocol)	Placebo Identically-looking placebo capsules to memantine were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Placebo: Identically looking placebo capsules bid (after a four-week regimen designed to mimic standard dose titration protocol)
Overall Study Adverse Event	3	2
Overall Study Lost to Follow-up	4	1
Overall Study Removed from analysis due to low medication compliance	1	0

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Placebo n=79 Participants Identically looking placebo capsules to memantine were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Placebo: Identically looking placebo capsules bid (after a four-week regimen designed to mimic standard dose titration protocol)	Memantine n=81 Participants Memantine capsules were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Memantine: Encapsulated Memantine 10 mg bid (after four-week standard dose titration protocol)	Total n=160 Participants Total of all reporting groups
Sex: Female, Male Female	43 Participants n=79 Participants	43 Participants n=81 Participants	86 Participants n=160 Participants
Sex: Female, Male Male	36 Participants n=79 Participants	38 Participants n=81 Participants	74 Participants n=160 Participants
Age, Continuous	20.3 years STANDARD_DEVIATION 4.2 • n=79 Participants	20.4 years STANDARD_DEVIATION 4.7 • n=81 Participants	20.35 years STANDARD_DEVIATION 4.5 • n=160 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United States	32 participants n=79 Participants	35 participants n=81 Participants	67 participants n=160 Participants
Region of Enrollment Brazil	47 participants n=79 Participants	46 participants n=81 Participants	93 participants n=160 Participants
Mother's Years of Education	14.6 Years of education STANDARD_DEVIATION 3.9 • n=79 Participants	14.4 Years of education STANDARD_DEVIATION 3.8 • n=81 Participants	14.5 Years of education STANDARD_DEVIATION 3.8 • n=160 Participants
Father's Years of Education	13.8 Years of education STANDARD_DEVIATION 4.3 • n=79 Participants	14.5 Years of education STANDARD_DEVIATION 3.9 • n=81 Participants	14.3 Years of education STANDARD_DEVIATION 4.1 • n=160 Participants
Hypothyroidism	37 Participants n=79 Participants	41 Participants n=81 Participants	78 Participants n=160 Participants
Obesity	24 Participants n=79 Participants	25 Participants n=81 Participants	49 Participants n=160 Participants
Sleep apnea	11 Participants n=79 Participants	13 Participants n=81 Participants	24 Participants n=160 Participants
Diabetes	0 Participants n=79 Participants	3 Participants n=81 Participants	3 Participants n=160 Participants
California Verbal Learning Test Second Edition-Short Form (CVLT-II-sf) total free recall score	14.2 units on a scale STANDARD_DEVIATION 7.1 • n=79 Participants	12.8 units on a scale STANDARD_DEVIATION 6.4 • n=81 Participants	13.5 units on a scale STANDARD_DEVIATION 6.7 • n=160 Participants
Matrices Subtest of the Differential Ability Scales-II (DAS-II)	51.5 units on a scale STANDARD_DEVIATION 12.3 • n=79 Participants	51.4 units on a scale STANDARD_DEVIATION 13.4 • n=81 Participants	51.4 units on a scale STANDARD_DEVIATION 12.9 • n=160 Participants
Scales of Independent Behavior-Revised (SIB-R) broad independence standard score	45.9 units on a scale STANDARD_DEVIATION 25.7 • n=79 Participants	43 units on a scale STANDARD_DEVIATION 22.8 • n=81 Participants	44.4 units on a scale STANDARD_DEVIATION 23.2 • n=160 Participants
Peabody Picture Vocabulary Test-IV (PPVT-IV)	46.6 units on a scale STANDARD_DEVIATION 20.7 • n=79 Participants	45.4 units on a scale STANDARD_DEVIATION 18.6 • n=81 Participants	46 units on a scale STANDARD_DEVIATION 19.7 • n=160 Participants
Level of intellectual disability (Severe)	22 Participants n=79 Participants	30 Participants n=81 Participants	52 Participants n=160 Participants
Level of intellectual disability (Moderate)	29 Participants n=79 Participants	25 Participants n=81 Participants	54 Participants n=160 Participants
Level of intellectual disability (Mild to typical)	28 Participants n=79 Participants	26 Participants n=81 Participants	54 Participants n=160 Participants

PRIMARY outcome

Timeframe: baseline and 16 weeks from start of treatment

Population: The analysis population consisted of participants who completed 16 weeks of treatment and had neuropsychological assessments at baseline (T1) and after treatment (T2)

The primary efficacy measure is focused on episodic memory. The CVLT-II short form assesses supraspan word learning ability as an index of episodic verbal long-term memory. We hypothesize that treatment with memantine will produce significant improvements in this test. The main dependent variable selected, based on prior literature was the total number of target items correct summed across learning trials 1-4. The values for this measure have been recorded as change in score from baseline (T1) to after the treatment (T2). Scale Range: from 0 to 36; higher scores represent better outcomes.

Outcome measures

Measure	Placebo n=76 Participants Identically looking placebo capsules to memantine were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Placebo: Identically looking placebo capsules bid (after a four-week regimen designed to mimic standard dose titration protocol)	Memantine n=73 Participants Memantine capsules were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Memantine: Encapsulated Memantine 10 mg bid (after four-week standard dose titration protocol)
Efficacy of the Drug Memantine as Assessed by Change in Score on the California Verbal Learning Test-II (CVLT-II) Short Form Total Free Recall	3.3 score on a scale Standard Deviation 5.15	3.49 score on a scale Standard Deviation 4.5

SECONDARY outcome

Timeframe: baseline and 16 weeks from start of treatment

Population: The analysis population consisted of participants who completed 16 weeks of treatment and had neuropsychological assessments at baseline (T1) and after treatment (T2)

This is a measure of non-verbal memory that requires the participant to learn associations between an abstract visual pattern and its location. Two dependent variables have been selected: Total number of items correct on the first trial of each stage, and total number of stages completed. The values for this measure have been recorded as change in score from baseline (T1) to after the treatment (T2). The minimum value of the PAL Memory Score Scale is 0 and the maximum value is 21; higher scores mean better outcomes.

Outcome measures

Measure	Placebo n=76 Participants Identically looking placebo capsules to memantine were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Placebo: Identically looking placebo capsules bid (after a four-week regimen designed to mimic standard dose titration protocol)	Memantine n=73 Participants Memantine capsules were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Memantine: Encapsulated Memantine 10 mg bid (after four-week standard dose titration protocol)
Efficacy of the Drug Memantine as Assessed by Change in Score on the Paired Associates Learning (PAL) From the Cambridge Neuropsychological Test Automated Battery (CANTAB)	1 score on a scale Standard Deviation 3.76	0.67 score on a scale Standard Deviation 3.83

SECONDARY outcome

Timeframe: baseline and 16 weeks from start of treatment

Population: The analysis population consisted of participants who completed 16 weeks of treatment and had neuropsychological assessments at baseline (T1) and after treatment (T2).

This is a measure of rote short-term verbal memory. Total number of items correct were used as the dependent variable. The values for this measure have been recorded as change in score from baseline (T1) to after the treatment (T2). The minimum value for this scale is 0 and the maximum value is 38; higher scores mean a better outcome.

Outcome measures

Measure	Placebo n=76 Participants Identically looking placebo capsules to memantine were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Placebo: Identically looking placebo capsules bid (after a four-week regimen designed to mimic standard dose titration protocol)	Memantine n=73 Participants Memantine capsules were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Memantine: Encapsulated Memantine 10 mg bid (after four-week standard dose titration protocol)
Efficacy of the Drug Memantine as Assessed by Change in Score on the Recall of Digits Forward (From the Differential Ability Scales; DAS-II)	0.03 score on a scale Standard Deviation 2.37	-0.01 score on a scale Standard Deviation 1.93

SECONDARY outcome

Timeframe: baseline and 16 weeks from start of treatment

Population: The analysis population consisted of participants who completed 16 weeks of treatment and had neuropsychological assessments at baseline (T1) and after treatment (T2).

This is a measure of non-verbal memory. Total number correct across the two series of items presented was used as the dependent variable. We used the PRM total scale in this study, which represents the sum of the PRM correct scores (ranging from 0 to 24) and the PRM delayed scores (ranging from 0 to 24). Therefore, the range of the PRM total scale is from 0 to 48; higher values mean better outcomes.

Outcome measures

Measure	Placebo n=76 Participants Identically looking placebo capsules to memantine were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Placebo: Identically looking placebo capsules bid (after a four-week regimen designed to mimic standard dose titration protocol)	Memantine n=73 Participants Memantine capsules were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Memantine: Encapsulated Memantine 10 mg bid (after four-week standard dose titration protocol)
Efficacy of the Drug Memantine as Assessed by Change in Score on the Pattern Recognition Memory (PRM; Part of the Cambridge Neuropsychological Test Automated Battery -- CANTAB)	0.45 score on a scale Standard Deviation 4.24	-0.05 score on a scale Standard Deviation 4.48

SECONDARY outcome

Timeframe: baseline and 16 weeks from start of treatment

Population: The analysis population consisted of participants who completed 16 weeks of treatment and had neuropsychological assessments at baseline (T1) and after treatment (T2).

The test requires participants to search under a series of colored boxes to locate a "blue token" hidden underneath one of them. During a series of trials, the participant is told that the token will be in a new location each time and that they should not go back to a location he or she has looked in previously. The main dependent variable was the total number of errors ("between errors"), which indexes the number of times a participant went back to a box where a token had already been found, lower scores mean better performance. The minimum value of the Spatial Working Memory scale is 0 and the maximum value is 137 (which was computed as the equivalent to -4 standard deviations from the mean of this measure); higher scores mean worse outcomes. The values for this measure have been recorded as change in score from baseline (T1) to after the treatment (T2).

Outcome measures

Measure	Placebo n=76 Participants Identically looking placebo capsules to memantine were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Placebo: Identically looking placebo capsules bid (after a four-week regimen designed to mimic standard dose titration protocol)	Memantine n=73 Participants Memantine capsules were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Memantine: Encapsulated Memantine 10 mg bid (after four-week standard dose titration protocol)
Efficacy of the Drug Memantine as Assessed by Change in Score on the Spatial Working Memory (Part of the Cambridge Neuropsychological Test Automated Battery -- CANTAB)	-0.09 score on a scale Standard Deviation 11.99	-1.4 score on a scale Standard Deviation 11.66

SECONDARY outcome

Timeframe: baseline and 16 weeks from start of treatment

Population: The analysis population consisted of participants who completed 16 weeks of treatment and had neuropsychological assessments at baseline (T1) and after treatment (T2).

This measure is a computerized version of the Corsi Blocks task, a long-standing neuropsychological test. The main dependent variables selected for this test was the span length, which is the longest sequence of numbers recalled accurately. The minimum value of the Spatial Span Length Score Scale is 0 and the maximum value is 9; higher scores mean better outcomes. The values for this measure have been recorded as change in score from baseline (T1) to after the treatment (T2).

Outcome measures

Measure	Placebo n=76 Participants Identically looking placebo capsules to memantine were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Placebo: Identically looking placebo capsules bid (after a four-week regimen designed to mimic standard dose titration protocol)	Memantine n=73 Participants Memantine capsules were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Memantine: Encapsulated Memantine 10 mg bid (after four-week standard dose titration protocol)
Efficacy of the Drug Memantine as Assessed by Change in Score on the Spatial Span (Part of the Cambridge Neuropsychological Test Automated Battery -- CANTAB)	0.13 score on a scale Standard Deviation 1.30	0.03 score on a scale Standard Deviation 1.29

SECONDARY outcome

Timeframe: baseline and 16 weeks from start of treatment

Population: The analysis population consisted of participants who completed 16 weeks of treatment and had neuropsychological assessments at baseline (T1) and after treatment (T2). Notice that, for this specific test, some participants stopped midway.

This is a measure of inhibitory control, often used as a marker for prefrontal-striatal function integrity. Specifically, it measures the participant's ability to inhibit pre-potent behavioral responses that have been established by provision of prior "go" or "no-go" cues in a classical conditioning paradigm. The main dependent variables selected was speed of response of execution to Go targets. The minimum value of the speed of response of execution to Go targets is 280 milliseconds (ms) and the maximum value is 1000 ms; higher scores mean worse outcomes. The values for this measure have been recorded as change in score from baseline (T1) to after the treatment (T2).

Outcome measures

Measure	Placebo n=73 Participants Identically looking placebo capsules to memantine were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Placebo: Identically looking placebo capsules bid (after a four-week regimen designed to mimic standard dose titration protocol)	Memantine n=72 Participants Memantine capsules were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Memantine: Encapsulated Memantine 10 mg bid (after four-week standard dose titration protocol)
Efficacy of the Drug Memantine as Assessed by Change in Score on the The Go - No Go Task	-2.52 ms Standard Deviation 96.08	0.22 ms Standard Deviation 111.28

SECONDARY outcome

Timeframe: baseline and 16 weeks from start of treatment

Population: The analysis population consisted of all participants who started treatment and had good-quality ECGs before and after the start of memantine treatment, whether or not they completed the entire treatment.

Incidence of adverse events was monitored by clinical history, physical examinations, electrocardiograms (ECGs), clinical laboratory tests, the Screen for Childhood Anxiety Related Emotional Disorders (SCARED). Here, we report the analysis of the effect of memantine treatment on QTc intervals because of its clinical importance for this analysis for potential drug toxicity. QTc intervals ≥ 450 ms are generally considered long, and drug-induced QTc interval prolongations ≥ 60 ms are generally considered clinically relevant.

Outcome measures

Measure	Placebo n=71 Participants Identically looking placebo capsules to memantine were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Placebo: Identically looking placebo capsules bid (after a four-week regimen designed to mimic standard dose titration protocol)	Memantine n=65 Participants Memantine capsules were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Memantine: Encapsulated Memantine 10 mg bid (after four-week standard dose titration protocol)
Safety and Tolerability of the Drug Memantine as Assessed by Change in QTc Interval	-1.30 ms Standard Deviation 13.51	-0.11 ms Standard Deviation 12.38

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline and 16 weeks from start of treatment

Population: The analysis population consisted of participants who completed 16 weeks of treatment and had neuropsychological assessments at baseline (T1) and after treatment (T2).

This test provides a measure of non-verbal reasoning ability that requires subjects to visually inspect a matrix of 4 or 9 pictures that has a missing piece. Participants have to infer a rule or pattern in the stimuli and select the appropriate response from a range of 4-6 possibilities. Since age norms are not available for individuals older than 17y11m, the ability score will be used as the dependent variable. This is an intermediate score based on Rasch modeling that corrects for different items set being administered to participants. The minimum value of the DAS-II Rasch Score Scale is 0 and the maximum value is 153; higher scores mean better outcomes. The values for this measure have been recorded as change in score from baseline (T1) to after the treatment (T2).

Outcome measures

Measure	Placebo n=76 Participants Identically looking placebo capsules to memantine were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Placebo: Identically looking placebo capsules bid (after a four-week regimen designed to mimic standard dose titration protocol)	Memantine n=73 Participants Memantine capsules were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Memantine: Encapsulated Memantine 10 mg bid (after four-week standard dose titration protocol)
Intellectual Functioning of the Participants as Assessed by Change in Score on the Matrices Subtest of the Differential Ability Scales-II (DAS-II)	0.75 score on a scale Standard Deviation 9.22	2.66 score on a scale Standard Deviation 12.12

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline and 16 weeks from start of treatment

Population: The analysis population consisted of participants who completed 16 weeks of treatment and had neuropsychological assessments at baseline (T1) and after treatment (T2).

This is a measure of receptive syntax skills (Bishop, 1983). Participants are asked to point to a picture (out of 4) that corresponds to a phrase or sentence spoken by the examiner. The total number of items correct (rather than blocks passed) will be used as the dependent variable, following the administration manual's ceiling rule. The values for this measure have been recorded as change in score from baseline (T1) to after the treatment (T2). The minimum value of the scores is 0 and the maximum value is 40; with higher scores considered to be a better outcome.

Outcome measures

Measure	Placebo n=76 Participants Identically looking placebo capsules to memantine were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Placebo: Identically looking placebo capsules bid (after a four-week regimen designed to mimic standard dose titration protocol)	Memantine n=73 Participants Memantine capsules were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Memantine: Encapsulated Memantine 10 mg bid (after four-week standard dose titration protocol)
Linguistic Functioning of the Participants as Assessed by Change in Score on the Test for Reception of Grammar 2nd Edition (TROG-II)	0.49 score on a scale Standard Deviation 4.01	0.89 score on a scale Standard Deviation 3.39

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline and 16 weeks from start of treatment

Population: The analysis population consisted of participants who completed 16 weeks of treatment and had neuropsychological assessments at baseline (T1) and after treatment (T2).

This is a measure of receptive semantics, whereby the participant is asked to point to a picture (out of 4) that corresponds to a word spoken by the examiner. As this test has a 0.85 correlation with composite measures of Verbal IQ (i.e. from the Wechsler Intelligence Scale series), it can be used in conjunction with the Matrices subtest to estimate overall intellectual functioning. The total number of items correct was used as the dependent variable, following the administration manual's rules for basals and ceilings. The values for this measure have been recorded as change in score from baseline (T1) to after the treatment (T2). The minimum value for this scale is 0 and the maximum value is 192, higher scores mean a better outcome.

Outcome measures

Measure	Placebo n=76 Participants Identically looking placebo capsules to memantine were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Placebo: Identically looking placebo capsules bid (after a four-week regimen designed to mimic standard dose titration protocol)	Memantine n=73 Participants Memantine capsules were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Memantine: Encapsulated Memantine 10 mg bid (after four-week standard dose titration protocol)
Linguistic Functioning of the Participants as Assessed by Change in Score on the Peabody Picture Vocabulary Test-IV (PPVT-IV)	4.46 score on a scale Standard Deviation 12.96	5.63 score on a scale Standard Deviation 16.38

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline and 16 weeks from start of treatment

Population: The analysis population consisted of participants who completed 16 weeks of treatment and had neuropsychological assessments at baseline (T1) and after treatment (T2). Note that some participants chose not to undergo the questionnaire.

This is a measure of adaptive functioning that integrates information from 13 different domains (e.g., gross motor, social interaction, eating, toileting, dressing, personal self-care, etc.). It is in a questionnaire format, which a caregiver can complete while the participant is being tested. Standard scores for all indices will be derived from age norms that extend from birth to age 80, as these were used as dependent variables. We report here on the Broad Independence Score recorded as change in score from baseline (T1) to after the treatment (T2). The minimum value of the SIB-R Score Scale in this study was -24 (this number is below 0 because -24 was the minimum value for the worst performing participant in the trial) and the maximum value of this scale is 153; higher scores mean better outcomes.

Outcome measures

Measure	Placebo n=67 Participants Identically looking placebo capsules to memantine were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Placebo: Identically looking placebo capsules bid (after a four-week regimen designed to mimic standard dose titration protocol)	Memantine n=65 Participants Memantine capsules were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Memantine: Encapsulated Memantine 10 mg bid (after four-week standard dose titration protocol)
Adaptive/Behavioral Functioning of the Participants as Assessed by Change in Score on the Scales of Independent Behavior-Revised (SIB-R)	6.88 score on a scale Standard Deviation 16.93	3.23 score on a scale Standard Deviation 13.32

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 44 other events

Deaths: 0 deaths

Memantine

Serious events: 0 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo n=79 participants at risk Identically looking placebo capsules to memantine were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Placebo: Identically looking placebo capsules bid (after a four-week regimen designed to mimic standard dose titration protocol)	Memantine n=81 participants at risk Memantine capsules were dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3. Memantine: Encapsulated Memantine 10 mg bid (after four-week standard dose titration protocol)
Infections and infestations Signs and symptoms of upper respiratory viral infection	15.2% 12/79 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.	11.1% 9/81 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.
General disorders Transient dizziness	7.6% 6/79 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.	9.9% 8/81 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.
Psychiatric disorders Anxiety	5.1% 4/79 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.	7.4% 6/81 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.
Psychiatric disorders Mood changes or irritability	6.3% 5/79 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.	2.5% 2/81 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.
Psychiatric disorders Mood changes or sadness	3.8% 3/79 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.	3.7% 3/81 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.
Psychiatric disorders Oppositional or aggressive behavior	2.5% 2/79 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.	1.2% 1/81 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.
General disorders Headache	3.8% 3/79 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.	3.7% 3/81 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.
General disorders Drowsiness	5.1% 4/79 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.	2.5% 2/81 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.
Gastrointestinal disorders Diarrhea	5.1% 4/79 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.	6.2% 5/81 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.
Gastrointestinal disorders Nausea or vomiting	2.5% 2/79 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.	3.7% 3/81 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.
General disorders Weakness or fatigue	1.3% 1/79 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.	3.7% 3/81 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.
General disorders Insomnia	0.00% 0/79 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.	3.7% 3/81 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.
Endocrine disorders Increase in thyroid-stimulating hormone levels	3.8% 3/79 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.	0.00% 0/81 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.
Renal and urinary disorders Urinary incontinence	1.3% 1/79 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.	1.2% 1/81 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.
Psychiatric disorders Increased self-talk	2.5% 2/79 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.	0.00% 0/81 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.
General disorders Increased appetite	2.5% 2/79 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.	0.00% 0/81 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.
Infections and infestations Tonsillitis	2.5% 2/79 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.	0.00% 0/81 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.
Psychiatric disorders Visual hallucinations	0.00% 0/79 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.	1.2% 1/81 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.
Infections and infestations Herpes simplex flair-up	0.00% 0/79 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.	1.2% 1/81 • From the beginning to the end of treatment, i.e., 16-18 weeks The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.

Additional Information

Melissa Stasko, JD, MA

Case Western Reserve University

Phone: 216-844-7281

Email: Melissa.Stasko@case.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place