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Efficacy and Safety of Memantine Hydrochloride in Enhancing the Cognitive Abilities of Young Adults With Down Syndrome

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ClinicalTrials.gov Identifier: NCT01112683
Recruitment Status : Completed
First Posted : April 28, 2010
Results First Posted : February 1, 2013
Last Update Posted : February 1, 2013
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
University of Colorado, Denver

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Down Syndrome
Interventions Drug: Memantine
Drug: Placebo
Enrollment 42
Recruitment Details 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.
Pre-assignment Details 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).
Arm/Group Title Memantine Placebo
Hide Arm/Group Description 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). These are identically-looking pills to the ones in the Memantine Arm
Period Title: Overall Study
Started 19 20
Completed 18 19
Not Completed 1 1
Arm/Group Title Memantine Placebo Total
Hide Arm/Group Description 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). These are identically-looking pills to the ones in the Memantine Arm Total of all reporting groups
Overall Number of Baseline Participants 19 20 39
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 20 participants 39 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
19
 100.0%
20
 100.0%
39
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 19 participants 20 participants 39 participants
23.27  (3.52) 22.60  (4.01) 22.93  (3.76)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 20 participants 39 participants
Female
12
  63.2%
13
  65.0%
25
  64.1%
Male
7
  36.8%
7
  35.0%
14
  35.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 19 participants 20 participants 39 participants
19 20 39
1.Primary Outcome
Title Changes in Neuropsychological Measures From Baseline to End of Study
Hide Description

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
Time Frame 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Memantine Placebo
Hide Arm/Group Description:
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).
These are identically-looking pills to the ones in the Memantine Arm
Overall Number of Participants Analyzed 18 19
Mean (90% Confidence Interval)
Unit of Measure: units on a scale
Pattern recognition memory pre/post diff scores
-0.22
(-1.95 to 1.50)
-0.84
(-2.52 to 0.83)
Paired associates task stages pre/post diff scores
0.56
(-0.07 to 1.04)
0
(-0.48 to 0.48)
Paired associates task 1st trial pre/post diff
0.39
(-1.05 to 1.83)
0.68
(-0.72 to 2.09)
CVLT Free Recall Total
5.84
(3.47 to 8.21)
2.53
(0.33 to 4.72)
Rivermead Behavioral Memory Test
1.3
(-0.56 to 3.16)
0.79
(-0.98 to 2.56)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Memantine, Placebo
Comments 20 subjects per group were expected to provide 60% power to detect a between-group mean difference of 1.2 correct patterns (change from baseline to week 16) on the Paired Associates Learning and to provide 40% power to detect a between-group mean difference of 1.2 patterns recognized on the Pattern Recognition Memory. A two-sided test at type I error rate of 5% was used. Sample size incorporated an inflation factor of 20% to account for ineligibility of 10% of randomized participants.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.403
Comments [Not Specified]
Method Mixed Models Analysis
Comments An alpha level of 0.05 or lower represents statistical significance, no correction was made for multiple comparisons to minimize type II errors.
2.Secondary Outcome
Title Changes in Benchmark Neuropsychological Measures From Baseline to End of Study
Hide Description

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.
Time Frame 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 treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Memantine Placebo
Hide Arm/Group Description:
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).
These are identically-looking pills to the ones in the Memantine Arm
Overall Number of Participants Analyzed 18 19
Mean (90% Confidence Interval)
Unit of Measure: scores on a scale
Peabody Picture Vocabulary Test-III
0.72
(-4.02 to 5.46)
-1.42
(-6.03 to 3.19)
Test for the Reception of Grammar
2.33
(-0.46 to 5.13)
-0.42
(-3.14 to 2.30)
Verbal Fluency (from the NEPSY)
0.78
(-1.18 to 2.74)
0.21
(-1.69 to 2.12)
Recall of Digits (DAS)
5.39
(-3.88 to 14.66)
-7.47
(-16.50 to 1.55)
Spatial working memory (strategy)
-0.06
(-1.70 to 1.59)
-1.47
(-3.07 to 0.12)
Scales of Independent Behavior Revised (SIB-R)
5.94
(2.02 to 9.85)
4.88
(1.21 to 8.55)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Memantine, Placebo
Comments No power calculations were performed for the secondary measures.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.371
Comments This P-Value refers to the SIB-R Broad independence score.
Method Mixed Models Analysis
Comments An alpha level of 0.05 or lower represents statistical significance, no correction was made for multiple comparisons to minimize type II errors.
3.Secondary Outcome
Title Changes of Safety and Tolerability Assessments at Baseline and End of Study
Hide Description Clinical 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.
Time Frame 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 treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Memantine Placebo
Hide Arm/Group Description:
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).
These are identically-looking pills to the ones in the Memantine Arm
Overall Number of Participants Analyzed 19 19
Measure Type: Number
Unit of Measure: participants
Increased anxiety 2 0
Transient dizziness 1 0
Echolalia 1 0
Androgenic alopecia 0 1
Time Frame 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.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Memantine Placebo
Hide Arm/Group Description 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). These are identically-looking pills to the ones in the Memantine Arm
All-Cause Mortality
Memantine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Memantine Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/19 (0.00%)      0/19 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Memantine Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/19 (15.79%)      1/19 (5.26%)    
Nervous system disorders     
Dizziness * 1  1/19 (5.26%)  1 0/19 (0.00%)  0
Psychiatric disorders     
Anxiety  1  2/19 (10.53%)  2 0/19 (0.00%)  0
Echolalia * 1  1/19 (5.26%)  1 0/19 (0.00%)  0
Skin and subcutaneous tissue disorders     
Androgenic alopecia * 1  0/19 (0.00%)  0 1/19 (5.26%)  1
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, SNOMED CT
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Alberto Costa
Organization: University of Colorado School of Medicine
Phone: 303-724-6007
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01112683     History of Changes
Other Study ID Numbers: 06-0934
06-0934 ( Other Identifier: Colorado Multiple Institutional Review Board )
First Submitted: April 23, 2010
First Posted: April 28, 2010
Results First Submitted: July 25, 2012
Results First Posted: February 1, 2013
Last Update Posted: February 1, 2013