Trial Outcomes & Findings for Efficacy and Safety of Memantine Hydrochloride in Enhancing the Cognitive Abilities of Young Adults With Down Syndrome (NCT NCT01112683)
NCT ID: NCT01112683
Last Updated: 2013-02-01
Results Overview
The hippocampus-dependent measures assessed in the present study are 1. Pattern recognition memory\* - Measures visual memory for non-namable designs; scale range in dataset 4-24; higher score indicates better performance 2. Paired associates task\* - Measures ability to learn visual associations between a picture and its location, and retention of this information over time; scale range in dataset 0-17; higher score indicates better performance 3. California Verbal Learning Test (CVLT) - Children's Version\*\* - Measures episodic verbal memory (sum of the items recalled over the 4 learning trials); scale range in dataset 0-35; higher score indicates better performance 4. Rivermead Behavioral Memory Test-Children's version\*\* - Measures episodic memory for visual information presented in context; scale range in dataset 1-20; higher score indicates better performance \* used in power analysis calculation of sample size \*\* secondary measures associated with the primary hypothesis
COMPLETED
PHASE4
42 participants
These neuropsychological measures will be assessed one time 24 hours before the beginning of treatment and then a second time 16 weeks from the beginning of the treatment
2013-02-01
Participant Flow
A total of 42 persons with DS from both genders and between the ages of 18 and 32 were recruited from the community. Thirty nine participants had a cytogenetic diagnostic of trisomy 21 and 3 had complete unbalanced Robertsonian translocations involving a 14 and 21 homologue, leading to an additional chromosome 21.
Two screened subjects were excluded from the trial before assignment to groups: 1 due to an unrelated medical issue and 1 because we could not find age/gender matching subject. And 1 dropped from the trial after randomization due to personal reasons (death in the family).
Participant milestones
| Measure |
Memantine
The drug dosage will follow memantine's standard titration schedule (i.e., 5 mg/d week one, 5 mg/BID week two, 5 \& 10 mg/d divided dose week three, 10mg/BID week four).
|
Placebo
These are identically-looking pills to the ones in the Memantine Arm
|
|---|---|---|
|
Overall Study
STARTED
|
19
|
20
|
|
Overall Study
COMPLETED
|
18
|
19
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Efficacy and Safety of Memantine Hydrochloride in Enhancing the Cognitive Abilities of Young Adults With Down Syndrome
Baseline characteristics by cohort
| Measure |
Memantine
n=19 Participants
The drug dosage will follow memantine's standard titration schedule (i.e., 5 mg/d week one, 5 mg/BID week two, 5 \& 10 mg/d divided dose week three, 10mg/BID week four).
|
Placebo
n=20 Participants
These are identically-looking pills to the ones in the Memantine Arm
|
Total
n=39 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
19 Participants
n=99 Participants
|
20 Participants
n=107 Participants
|
39 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age Continuous
|
23.27 years
STANDARD_DEVIATION 3.52 • n=99 Participants
|
22.60 years
STANDARD_DEVIATION 4.01 • n=107 Participants
|
22.93 years
STANDARD_DEVIATION 3.76 • n=206 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=99 Participants
|
13 Participants
n=107 Participants
|
25 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
14 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
19 participants
n=99 Participants
|
20 participants
n=107 Participants
|
39 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: These neuropsychological measures will be assessed one time 24 hours before the beginning of treatment and then a second time 16 weeks from the beginning of the treatmentPopulation: One participant dropped out of the study due to parent complaints of increased anxiety, and another was excluded from analyses due to side effects (increased and persistent anxiety) reported at study completion.
The hippocampus-dependent measures assessed in the present study are 1. Pattern recognition memory\* - Measures visual memory for non-namable designs; scale range in dataset 4-24; higher score indicates better performance 2. Paired associates task\* - Measures ability to learn visual associations between a picture and its location, and retention of this information over time; scale range in dataset 0-17; higher score indicates better performance 3. California Verbal Learning Test (CVLT) - Children's Version\*\* - Measures episodic verbal memory (sum of the items recalled over the 4 learning trials); scale range in dataset 0-35; higher score indicates better performance 4. Rivermead Behavioral Memory Test-Children's version\*\* - Measures episodic memory for visual information presented in context; scale range in dataset 1-20; higher score indicates better performance \* used in power analysis calculation of sample size \*\* secondary measures associated with the primary hypothesis
Outcome measures
| Measure |
Memantine
n=18 Participants
The drug dosage will follow memantine's standard titration schedule (i.e., 5 mg/d week one, 5 mg/BID week two, 5 \& 10 mg/d divided dose week three, 10mg/BID week four).
|
Placebo
n=19 Participants
These are identically-looking pills to the ones in the Memantine Arm
|
|---|---|---|
|
Changes in Neuropsychological Measures From Baseline to End of Study
Pattern recognition memory pre/post diff scores
|
-0.22 units on a scale
Interval -1.95 to 1.5
|
-0.84 units on a scale
Interval -2.52 to 0.83
|
|
Changes in Neuropsychological Measures From Baseline to End of Study
Paired associates task stages pre/post diff scores
|
0.56 units on a scale
Interval -0.07 to 1.04
|
0 units on a scale
Interval -0.48 to 0.48
|
|
Changes in Neuropsychological Measures From Baseline to End of Study
Paired associates task 1st trial pre/post diff
|
0.39 units on a scale
Interval -1.05 to 1.83
|
0.68 units on a scale
Interval -0.72 to 2.09
|
|
Changes in Neuropsychological Measures From Baseline to End of Study
CVLT Free Recall Total
|
5.84 units on a scale
Interval 3.47 to 8.21
|
2.53 units on a scale
Interval 0.33 to 4.72
|
|
Changes in Neuropsychological Measures From Baseline to End of Study
Rivermead Behavioral Memory Test
|
1.3 units on a scale
Interval -0.56 to 3.16
|
0.79 units on a scale
Interval -0.98 to 2.56
|
SECONDARY outcome
Timeframe: Benchmark neuropsychological measures will be assessed one time 24 hours before the beginning of treatment and then a second time 16 weeks from the beginning of the treatmentPopulation: These measures were not predicted to change due to memantine treatment. Measures of non-verbal reasoning, receptive language and vocabulary, short-term phonological memory, verbal and non-verbal working memory and adaptive/behavioral functioning were included.
The neuropsychological benchmark measures assessed in this study are 1. Peabody Picture Vocabulary Test-III (PPVT-III; range: -27.00 to 23.00) 2. Test for the Reception of Grammar (TROG; range: -13.00 to 19.00) 3. Verbal Fluency (from the Developmental Neuropsychological Assessment (NEPSY); range: -13.00 to 10.00) 4. Recall of Digits (Differential Ability Scales; DAS; -50.00 to 59.00) 5. Spatial working memory (SWM; part of the Cambridge Neuropsychological Test Automated Battery, or CANTAB; range: -9.00 to 8.00) 6. Scales of Independent Behavior Revised (SIB-R; -12.00 to 26.00) All listed values represent differences in scores obtained at baseline subtracted from scores at 16-weeks of treatment. With the exception of the spatial working memory, for all measures, higher values represent better outcome. For the spatial working memory, lower values represent better outcome.
Outcome measures
| Measure |
Memantine
n=18 Participants
The drug dosage will follow memantine's standard titration schedule (i.e., 5 mg/d week one, 5 mg/BID week two, 5 \& 10 mg/d divided dose week three, 10mg/BID week four).
|
Placebo
n=19 Participants
These are identically-looking pills to the ones in the Memantine Arm
|
|---|---|---|
|
Changes in Benchmark Neuropsychological Measures From Baseline to End of Study
Peabody Picture Vocabulary Test-III
|
0.72 scores on a scale
Interval -4.02 to 5.46
|
-1.42 scores on a scale
Interval -6.03 to 3.19
|
|
Changes in Benchmark Neuropsychological Measures From Baseline to End of Study
Test for the Reception of Grammar
|
2.33 scores on a scale
Interval -0.46 to 5.13
|
-0.42 scores on a scale
Interval -3.14 to 2.3
|
|
Changes in Benchmark Neuropsychological Measures From Baseline to End of Study
Verbal Fluency (from the NEPSY)
|
0.78 scores on a scale
Interval -1.18 to 2.74
|
0.21 scores on a scale
Interval -1.69 to 2.12
|
|
Changes in Benchmark Neuropsychological Measures From Baseline to End of Study
Recall of Digits (DAS)
|
5.39 scores on a scale
Interval -3.88 to 14.66
|
-7.47 scores on a scale
Interval -16.5 to 1.55
|
|
Changes in Benchmark Neuropsychological Measures From Baseline to End of Study
Spatial working memory (strategy)
|
-0.06 scores on a scale
Interval -1.7 to 1.59
|
-1.47 scores on a scale
Interval -3.07 to 0.12
|
|
Changes in Benchmark Neuropsychological Measures From Baseline to End of Study
Scales of Independent Behavior Revised (SIB-R)
|
5.94 scores on a scale
Interval 2.02 to 9.85
|
4.88 scores on a scale
Interval 1.21 to 8.55
|
SECONDARY outcome
Timeframe: Safety and tolerability assessments will be performed at three time points: 1) 1-7 days before beginning of treatment; 2) after 8 weeks from the beginning of the treatment; and 3) 16-17 weeks from the beginning of the treatmentClinical history and physical examinations, electrocardiograms (ECGs), comprehensive clinical laboratory tests, and incidence of adverse event recording. The comprehensive clinical laboratory tests will include assessments of liver and kidney function, electrolytes, acid/base balance, and blood glucose and proteins. In addition, pregnancy tests will be performed on all female participants of childbearing potential.
Outcome measures
| Measure |
Memantine
n=19 Participants
The drug dosage will follow memantine's standard titration schedule (i.e., 5 mg/d week one, 5 mg/BID week two, 5 \& 10 mg/d divided dose week three, 10mg/BID week four).
|
Placebo
n=19 Participants
These are identically-looking pills to the ones in the Memantine Arm
|
|---|---|---|
|
Changes of Safety and Tolerability Assessments at Baseline and End of Study
Increased anxiety
|
2 participants
|
0 participants
|
|
Changes of Safety and Tolerability Assessments at Baseline and End of Study
Transient dizziness
|
1 participants
|
0 participants
|
|
Changes of Safety and Tolerability Assessments at Baseline and End of Study
Echolalia
|
1 participants
|
0 participants
|
|
Changes of Safety and Tolerability Assessments at Baseline and End of Study
Androgenic alopecia
|
0 participants
|
1 participants
|
Adverse Events
Memantine
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Memantine
n=19 participants at risk
The drug dosage will follow memantine's standard titration schedule (i.e., 5 mg/d week one, 5 mg/BID week two, 5 \& 10 mg/d divided dose week three, 10mg/BID week four).
|
Placebo
n=19 participants at risk
These are identically-looking pills to the ones in the Memantine Arm
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Androgenic alopecia
|
0.00%
0/19 • Adverse event data were collected from the first day of treatment up to two weeks after the final week (16th week) of treatment, for a total of 18 weeks.
|
5.3%
1/19 • Number of events 1 • Adverse event data were collected from the first day of treatment up to two weeks after the final week (16th week) of treatment, for a total of 18 weeks.
|
|
Psychiatric disorders
Anxiety
|
10.5%
2/19 • Number of events 2 • Adverse event data were collected from the first day of treatment up to two weeks after the final week (16th week) of treatment, for a total of 18 weeks.
|
0.00%
0/19 • Adverse event data were collected from the first day of treatment up to two weeks after the final week (16th week) of treatment, for a total of 18 weeks.
|
|
Nervous system disorders
Dizziness
|
5.3%
1/19 • Number of events 1 • Adverse event data were collected from the first day of treatment up to two weeks after the final week (16th week) of treatment, for a total of 18 weeks.
|
0.00%
0/19 • Adverse event data were collected from the first day of treatment up to two weeks after the final week (16th week) of treatment, for a total of 18 weeks.
|
|
Psychiatric disorders
Echolalia
|
5.3%
1/19 • Number of events 1 • Adverse event data were collected from the first day of treatment up to two weeks after the final week (16th week) of treatment, for a total of 18 weeks.
|
0.00%
0/19 • Adverse event data were collected from the first day of treatment up to two weeks after the final week (16th week) of treatment, for a total of 18 weeks.
|
Additional Information
Dr. Alberto Costa
University of Colorado School of Medicine
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place