Down Syndrome Memantine Follow-up Study

Sponsor
University Hospitals Cleveland Medical Center (Other)
Overall Status
Completed
CT.gov ID
NCT02304302
Collaborator
Alana USA Foundation (Other)
160
2
2
69.7
80
1.1

Study Details

Study Description

Brief Summary

The purpose of this research study is to learn if the medication Memantine Hydrochloride (the study medication) can help adolescents and young adults with Down syndrome. Dr. Alberto Costa and his research team want to see if a 16-week treatment with this medication can improve the participant's ability to learn and remember things. In this study, memantine hydrochloride will be used. Thus, the researchers want to learn whether the study drug can help improve memory in young adults with Down syndrome. To test the effect of the study medicine, half of the people in the study will receive the study medicine and half will receive a placebo (an inactive substance). Memantine is an approved medication to treat memory and thinking problems in persons with Alzheimer disease. However, little is known about the effect of this medication in persons with Down syndrome and it has not been approved for use in persons with Down syndrome.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This study seeks to investigate if the medication Memantine Hydrochloride can help young adults with Down syndrome. Two hundred persons with Down syndrome from both genders and between 15 and 32 years of age will be recruited from two sites: Cleveland, OH, USA and São Paulo, SP, Brazil. Participants will be assigned randomly to either a placebo group or a group taking the active medication with a 50% probability of being on either group. Neither the participants nor the investigators will know who will be taking the study medication and who will be taking the placebo during the study. Only the investigational pharmacist will have access to this information.

Up to 60 people with Down syndrome of the recruited study participants will take part on an optional magnetic resonance imaging (MRI) study. This investigation is aimed at helping to make the EEG study more precise and to find out whether the study medication has any significant effect on the structure of the brain.

Additionally, we will recruit a control group of 60 age- and gender-matched participants without Down syndrome. The goal is to investigate how different groups of people activate their brains when they hear or see something, and if he can use high-density EEG and MRI to see how this study medication works in persons with Down syndrome. In other words, this additional control group should help us ascertain which parts of the test results are due to a person having Down syndrome and which ones are not. Persons without Down syndrome will only come for one EEG visit and one MRI visit, and not be asked to take the study medication.

The visits for the participants with Down syndrome will be as follows:

Screening visit (approximately 2-hour long). The subject will be asked about his/her health, medical history, social background, and work background, as well as some simple questions to determine performance on tests of memory and function that are part of this study. Informed consent and assent will be obtained in this visit. At the end of this visit, an EEG machine will be used to access brain responses to different auditory and visual stimuli. Some will be asked if they would be willing to have an MRI performed, but this portion is not imperative.

A urine sample will be collected and used to obtain cells that will be kept frozen for potential future studies. If the date of the screening visit is not convenient, this sample can be collected during any of the next five visits.

Visit 1 (approximately 1 hour). Pulse, blood pressure, and an electrocardiogram (ECG) will be taken. At the end of the visit, urine and blood samples will be taken. Pregnancy will also be checked.

Visit 2 (2-3 hours). Tests of memory, learning, and reasoning skills will be conducted before the start of the study medicine or placebo. At the end of this visit, a 60-day supply of either the study medicine or the placebo will be given. This will need to be taken for 16 weeks.

Visit 3 (approximately 30 minutes). Eight weeks after the beginning of the treatment, the participant will return to assess how she/he is doing under the treatment. Pulse, blood pressure, a physical exam, and pregnancy will be checked. At this visit, another supply of study medicine will be given.

Visit 4 (2-3 hours). Sixteen weeks after starting the medicine, the participant will take a second series of tests in learning, memory, and reasoning skills to find out whether there were any changes in these skills.

Visit 5 (approximately 1 hour). In the 16th or 17th week after starting the medicine, the participant will meet one more time with the doctor from visits 1 and 3. Vital signs, a physical exam, and an ECG will be taken, as well as a blood sample to ensure nothing has changed with the participant's general health. For women, a pregnancy test will be performed.

If for some reason the subject withdraws from this study prior to Visit 5, he/she will be asked to return to the clinic for a "Treatment Discontinuation Visit." In addition, if the participant discontinues the medication prior to the end of the study, he/she will be asked to complete a "Retrieved Dropout Visit" on the date that should have represented Visit 5. Study medication will not be provided beyond the study period.

Study Design

Study Type:
Interventional
Actual Enrollment :
160 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Phase II Multicenter 16-Week Randomized Double Blind Placebo-Controlled Evaluation of the Efficacy, Tolerability and Safety of Memantine Hydrochloride on Enhancing the Cognitive Abilities of Adolescents and Young Adults With Down Syndrome
Study Start Date :
Oct 1, 2014
Actual Primary Completion Date :
Jul 22, 2020
Actual Study Completion Date :
Jul 22, 2020

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo

Identically-looking placebo pills to memantine will be 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.

Drug: Placebo
Identically looking placebo capsules bid (after a four-week regimen designed to mimic standard dose titration protocol)
Other Names:
  • Inactive Capsules
  • Experimental: Memantine

    Memantine will be 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.

    Drug: Memantine
    Encapsulated Namenda 10 mg bid (after four-week standard dose titration protocol)
    Other Names:
  • Namenda
  • Outcome Measures

    Primary Outcome Measures

    1. 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 [baseline and 16 weeks from start of treatment]

      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.

    Secondary Outcome Measures

    1. 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) [baseline and 16 weeks from start of treatment]

      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.

    2. Efficacy of the Drug Memantine as Assessed by Change in Score on the Recall of Digits Forward (From the Differential Ability Scales; DAS-II) [baseline and 16 weeks from start of treatment]

      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.

    3. 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) [baseline and 16 weeks from start of treatment]

      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.

    4. 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) [baseline and 16 weeks from start of treatment]

      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).

    5. Efficacy of the Drug Memantine as Assessed by Change in Score on the Spatial Span (Part of the Cambridge Neuropsychological Test Automated Battery -- CANTAB) [baseline and 16 weeks from start of treatment]

      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).

    6. Efficacy of the Drug Memantine as Assessed by Change in Score on the The Go - No Go Task [baseline and 16 weeks from start of treatment]

      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).

    7. Safety and Tolerability of the Drug Memantine as Assessed by Change in QTc Interval [baseline and 16 weeks from start of 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.

    Other Outcome Measures

    1. Intellectual Functioning of the Participants as Assessed by Change in Score on the Matrices Subtest of the Differential Ability Scales-II (DAS-II) [baseline and 16 weeks from start of treatment]

      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).

    2. Linguistic Functioning of the Participants as Assessed by Change in Score on the Test for Reception of Grammar 2nd Edition (TROG-II) [baseline and 16 weeks from start of treatment]

      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.

    3. Linguistic Functioning of the Participants as Assessed by Change in Score on the Peabody Picture Vocabulary Test-IV (PPVT-IV) [baseline and 16 weeks from start of treatment]

      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.

    4. Adaptive/Behavioral Functioning of the Participants as Assessed by Change in Score on the Scales of Independent Behavior-Revised (SIB-R) [baseline and 16 weeks from start of treatment]

      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.

    5. Exploratory Study of Electroencephalographic (EEG) Recordings of Evoked Potentials as Potential Biomarkers for the Severity of the Cognitive Disability Associated to Down Syndrome and for the Efficacy of the Memantine Treatment [baseline and 16 weeks from start of treatment]

      Auditory and visual evoked potential experiments will search for significant differences in peak amplitude and latency of MMNs in persons with Down syndrome in relation to typically developing persons without Down syndrome, and in participants with Down syndrome before and after memantine treatment. As of this report date, the analysis of this exploratory measure has not yet been performed.

    6. Exploratory Study of Magnetic Resonance Imaging (MRI) as Potential Biomarkers for the Severity of the Cognitive Disability Associated to Down Syndrome and for the Efficacy of the Memantine Treatment [baseline and 16 weeks from start of treatment]

      MRI studies will be to provide precise source localization for the high-density EEG recordings of evoked potentials in a subset of 30-60 participants of this trial. In addition, these experiments will also produce high resolution sagittal slice images of the hippocampus and simple connectivity data sets. We were not able to collect data from enough participants of this study to perform any meaningful statistical analysis related to this exploratory measure.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    15 Years to 32 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
    • Cytogenetically documented Trisomy 21 or Complete Unbalanced Translocation of Chromosome 21. Mosaic Trisomy 21 and partial translocations will be excluded from the study

    • No pregnancy by serum testing at screening. Females of child-bearing potential, sexually active must be practicing a reliable method of birth control. Urine pregnancy tests will be done at the 2 follow-up medical visits

    • Laboratory findings within normal limits or judged clinically insignificant at baseline

    • Vital signs within normal limits for age. Stable, medically treated hypotension will be allowed

    • ECG must demonstrate predominately normal sinus rhythm. Minor abnormalities documented as clinically insignificant will be allowed

    • Participants and their authorized representatives will provide written informed consent

    • Participants who have received any experimental drug for Down syndrome must undergo a washout

    • All participants must: Be in general good health as judged by the investigators; Be able to swallow oral medication; Have a reliable caregiver or family member who agrees to accompany participant to all visits, provide information about the participant as required by the protocol, and ensure compliance with the medication schedule; Be sufficiently proficient in English (USA) or Portuguese (Brazil) to reliably complete the study assessments

    • Age and gender matching participants without Down syndrome, must be: Males or females without Down syndrome aged-matching (within 3 years) participants with Down syndrome whom they are expected to serve as controls

    Exclusion Criteria:
    • Participant weighing less than 40 kg

    • Current psychiatric or neurologic diagnosis other than Down syndrome (e.g., major depressive disorder, schizophrenia, bipolar disorder, autism, Alzheimer disease)

    • Current treatment with psychotropic drugs

    • Drug or alcohol abuse or dependence

    • Significant suicide risk or who would require treatment with electro-convulsive therapy or with psychotropic drugs during the study or who have received treatment with a depot neuroleptic drug within 6 months of entering the study.

    • Current or expected (within the next 6 months) hospitalization or residence in a skilled nursing facility (may reside in group homes or other residential settings with no skilled nursing)

    • Active or clinically significant conditions affecting absorption, distribution, or metabolism of study drug (e.g. inflammatory bowel disease or celiac disease)

    • Significant allergies to or other significant intolerance of memantine therapy, its ingredients, or with contraindications to memantine therapy as stated in the prescribing information

    • Participants who are expected to require general anesthetics during the course of the study

    • Presence or recent history of seizure disorder (< 3 years).

    • Clinically significant and/or clinically unstable systemic disease. (Those with controlled hypothyroidism must be on a stable dose of medication for at least 3 months prior to screening and have normal serum T-4 and TSH at screening; and those with controlled diabetes mellitus must have an HbA1c of < 8.0% and a random serum glucose value of < 170 mg/dl)

    • Severe infections or a major surgical operation within 3 months prior to screening

    • History of persistent cognitive deficits immediately following head trauma.

    • Donation of blood or blood products less that 30 days prior to screening, while participating in the study, or four weeks after completion of the study

    • Inability to comply with the protocol or perform the outcomes measures due to significant hearing or visual impairment or other issues judged relevant by the investigators

    • Exclusion criteria for controls without Down syndrome: History of substance abuse, major psychiatric disorder, attention deficit disorder, or learning disability; Beck Depression Score greater than 10; Exclusion criteria specific to MR scanning; Pregnancy; Neurologic history

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University Hospitals Case Medical Center Cleveland Ohio United States 44106
    2 Sociedade Beneficente Israelita Brasileira Albert Einstein São Paulo SP Brazil 05652- 900

    Sponsors and Collaborators

    • University Hospitals Cleveland Medical Center
    • Alana USA Foundation

    Investigators

    • Principal Investigator: Alberto C Costa, MD, PhD, University Hospitals Cleveland Medical Center
    • Study Director: Stephen L Ruedrich, MD, University Hospitals Cleveland Medical Center

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Dr. Alberto Costa, MD, PhD, Professor of Pediatric Neurology, University Hospitals Cleveland Medical Center
    ClinicalTrials.gov Identifier:
    NCT02304302
    Other Study ID Numbers:
    • 121971
    First Posted:
    Dec 1, 2014
    Last Update Posted:
    Apr 5, 2022
    Last Verified:
    Apr 1, 2022
    Keywords provided by Dr. Alberto Costa, MD, PhD, Professor of Pediatric Neurology, University Hospitals Cleveland Medical Center
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Placebo Memantine
    Arm/Group Description 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 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)
    Period Title: Overall Study
    STARTED 79 81
    COMPLETED 76 73
    NOT COMPLETED 3 8

    Baseline Characteristics

    Arm/Group Title Placebo Memantine Total
    Arm/Group Description 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 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 of all reporting groups
    Overall Participants 79 81 160
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    20.3
    (4.2)
    20.4
    (4.7)
    20.35
    (4.5)
    Sex: Female, Male (Count of Participants)
    Female
    43
    54.4%
    43
    53.1%
    86
    53.8%
    Male
    36
    45.6%
    38
    46.9%
    74
    46.3%
    Race and Ethnicity Not Collected (Count of Participants)
    Count of Participants [Participants]
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    32
    40.5%
    35
    43.2%
    67
    41.9%
    Brazil
    47
    59.5%
    46
    56.8%
    93
    58.1%
    Mother's Years of Education (Years of education) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years of education]
    14.6
    (3.9)
    14.4
    (3.8)
    14.5
    (3.8)
    Father's Years of Education (Years of education) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years of education]
    13.8
    (4.3)
    14.5
    (3.9)
    14.3
    (4.1)
    Hypothyroidism (Count of Participants)
    Count of Participants [Participants]
    37
    46.8%
    41
    50.6%
    78
    48.8%
    Obesity (Count of Participants)
    Count of Participants [Participants]
    24
    30.4%
    25
    30.9%
    49
    30.6%
    Sleep apnea (Count of Participants)
    Count of Participants [Participants]
    11
    13.9%
    13
    16%
    24
    15%
    Diabetes (Count of Participants)
    Count of Participants [Participants]
    0
    0%
    3
    3.7%
    3
    1.9%
    California Verbal Learning Test Second Edition-Short Form (CVLT-II-sf) total free recall score (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    14.2
    (7.1)
    12.8
    (6.4)
    13.5
    (6.7)
    Matrices Subtest of the Differential Ability Scales-II (DAS-II) (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    51.5
    (12.3)
    51.4
    (13.4)
    51.4
    (12.9)
    Scales of Independent Behavior-Revised (SIB-R) broad independence standard score (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    45.9
    (25.7)
    43
    (22.8)
    44.4
    (23.2)
    Peabody Picture Vocabulary Test-IV (PPVT-IV) (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    46.6
    (20.7)
    45.4
    (18.6)
    46
    (19.7)
    Level of intellectual disability (Severe) (Count of Participants)
    Count of Participants [Participants]
    22
    27.8%
    30
    37%
    52
    32.5%
    Level of intellectual disability (Moderate) (Count of Participants)
    Count of Participants [Participants]
    29
    36.7%
    25
    30.9%
    54
    33.8%
    Level of intellectual disability (Mild to typical) (Count of Participants)
    Count of Participants [Participants]
    28
    35.4%
    26
    32.1%
    54
    33.8%

    Outcome Measures

    1. Primary Outcome
    Title 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
    Description 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.
    Time Frame baseline and 16 weeks from start of treatment

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of participants who completed 16 weeks of treatment and had neuropsychological assessments at baseline (T1) and after treatment (T2)
    Arm/Group Title Placebo Memantine
    Arm/Group Description Identically looking placebo pills 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 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)
    Measure Participants 76 73
    Mean (Standard Deviation) [score on a scale]
    3.3
    (5.15)
    3.49
    (4.5)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Memantine
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.61
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.34
    Confidence Interval (2-Sided) 95%
    -0.98 to 1.67
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title 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)
    Description 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.
    Time Frame baseline and 16 weeks from start of treatment

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of participants who completed 16 weeks of treatment and had neuropsychological assessments at baseline (T1) and after treatment (T2)
    Arm/Group Title Placebo Memantine
    Arm/Group Description Identically looking placebo pills 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 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)
    Measure Participants 76 73
    Mean (Standard Deviation) [score on a scale]
    1
    (3.76)
    0.67
    (3.83)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Memantine
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.57
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.32
    Confidence Interval (2-Sided) 95%
    -1.43 to 0.80
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Efficacy of the Drug Memantine as Assessed by Change in Score on the Recall of Digits Forward (From the Differential Ability Scales; DAS-II)
    Description 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.
    Time Frame baseline and 16 weeks from start of treatment

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of participants who completed 16 weeks of treatment and had neuropsychological assessments at baseline (T1) and after treatment (T2).
    Arm/Group Title Placebo Memantine
    Arm/Group Description 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 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)
    Measure Participants 76 73
    Mean (Standard Deviation) [score on a scale]
    0.03
    (2.37)
    -0.01
    (1.93)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Memantine
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.91
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Median Difference (Net)
    Estimated Value -0.04
    Confidence Interval (2-Sided) 95%
    -0.74 to 0.66
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title 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)
    Description 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.
    Time Frame baseline and 16 weeks from start of treatment

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of participants who completed 16 weeks of treatment and had neuropsychological assessments at baseline (T1) and after treatment (T2).
    Arm/Group Title Placebo Memantine
    Arm/Group Description 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 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)
    Measure Participants 76 73
    Mean (Standard Deviation) [score on a scale]
    0.45
    (4.24)
    -0.05
    (4.48)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Memantine
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.48
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Median Difference (Final Values)
    Estimated Value -0.50
    Confidence Interval (2-Sided) 95%
    -1.91 to 0.91
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title 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)
    Description 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).
    Time Frame baseline and 16 weeks from start of treatment

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of participants who completed 16 weeks of treatment and had neuropsychological assessments at baseline (T1) and after treatment (T2).
    Arm/Group Title Placebo Memantine
    Arm/Group Description 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 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)
    Measure Participants 76 73
    Mean (Standard Deviation) [score on a scale]
    -0.09
    (11.99)
    -1.4
    (11.66)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Memantine
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.50
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -1.31
    Confidence Interval (2-Sided) 95%
    -5.14 to 2.53
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Efficacy of the Drug Memantine as Assessed by Change in Score on the Spatial Span (Part of the Cambridge Neuropsychological Test Automated Battery -- CANTAB)
    Description 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).
    Time Frame baseline and 16 weeks from start of treatment

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of participants who completed 16 weeks of treatment and had neuropsychological assessments at baseline (T1) and after treatment (T2).
    Arm/Group Title Placebo Memantine
    Arm/Group Description 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 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)
    Measure Participants 76 73
    Mean (Standard Deviation) [score on a scale]
    0.13
    (1.30)
    0.03
    (1.29)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Memantine
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.62
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -0.10
    Confidence Interval (2-Sided) 95%
    -0.52 to 0.32
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Efficacy of the Drug Memantine as Assessed by Change in Score on the The Go - No Go Task
    Description 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).
    Time Frame baseline and 16 weeks from start of treatment

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Placebo Memantine
    Arm/Group Description Identically-looking placebo pills to memantine will be 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 after a four-week regimen designed to mimic standard dose titration protocol) Memantine will be 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)
    Measure Participants 73 72
    Mean (Standard Deviation) [ms]
    -2.52
    (96.08)
    0.22
    (111.28)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Memantine
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.84
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 2.94
    Confidence Interval (2-Sided) 95%
    -25.32 to 31.20
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Safety and Tolerability of the Drug Memantine as Assessed by Change in QTc Interval
    Description 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.
    Time Frame baseline and 16 weeks from start of treatment

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Placebo Memantine
    Arm/Group Description 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 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)
    Measure Participants 71 65
    Mean (Standard Deviation) [ms]
    -1.30
    (13.51)
    -0.11
    (12.38)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Memantine
    Comments QTc interval duration was the independent variable, treatment and time were the categorical factors.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.24
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -3.04
    Confidence Interval (2-Sided) 95%
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Other Pre-specified Outcome
    Title Intellectual Functioning of the Participants as Assessed by Change in Score on the Matrices Subtest of the Differential Ability Scales-II (DAS-II)
    Description 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).
    Time Frame baseline and 16 weeks from start of treatment

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of participants who completed 16 weeks of treatment and had neuropsychological assessments at baseline (T1) and after treatment (T2).
    Arm/Group Title Placebo Memantine
    Arm/Group Description 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 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)
    Measure Participants 76 73
    Mean (Standard Deviation) [score on a scale]
    0.75
    (9.22)
    2.66
    (12.12)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Memantine
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.28
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 1.91
    Confidence Interval (2-Sided) 95%
    -1.57 to 5.39
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    10. Other Pre-specified Outcome
    Title Linguistic Functioning of the Participants as Assessed by Change in Score on the Test for Reception of Grammar 2nd Edition (TROG-II)
    Description 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.
    Time Frame baseline and 16 weeks from start of treatment

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of participants who completed 16 weeks of treatment and had neuropsychological assessments at baseline (T1) and after treatment (T2).
    Arm/Group Title Placebo Memantine
    Arm/Group Description 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 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)
    Measure Participants 76 73
    Mean (Standard Deviation) [score on a scale]
    0.49
    (4.01)
    0.89
    (3.39)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Memantine
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.51
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 0.40
    Confidence Interval (2-Sided) 95%
    -0.80 to 1.61
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    11. Other Pre-specified Outcome
    Title Linguistic Functioning of the Participants as Assessed by Change in Score on the Peabody Picture Vocabulary Test-IV (PPVT-IV)
    Description 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.
    Time Frame baseline and 16 weeks from start of treatment

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of participants who completed 16 weeks of treatment and had neuropsychological assessments at baseline (T1) and after treatment (T2).
    Arm/Group Title Placebo Memantine
    Arm/Group Description 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 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)
    Measure Participants 76 73
    Mean (Standard Deviation) [score on a scale]
    4.46
    (12.96)
    5.63
    (16.38)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Memantine
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.63
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value 1.17
    Confidence Interval (2-Sided) 95%
    -3.6 to 5.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    12. Other Pre-specified Outcome
    Title Adaptive/Behavioral Functioning of the Participants as Assessed by Change in Score on the Scales of Independent Behavior-Revised (SIB-R)
    Description 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.
    Time Frame baseline and 16 weeks from start of treatment

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Placebo Memantine
    Arm/Group Description 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 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)
    Measure Participants 67 65
    Mean (Standard Deviation) [score on a scale]
    6.88
    (16.93)
    3.23
    (13.32)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Memantine
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.17
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Net)
    Estimated Value -3.65
    Confidence Interval (2-Sided) 95%
    -8.91 to 1.61
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    13. Other Pre-specified Outcome
    Title Exploratory Study of Electroencephalographic (EEG) Recordings of Evoked Potentials as Potential Biomarkers for the Severity of the Cognitive Disability Associated to Down Syndrome and for the Efficacy of the Memantine Treatment
    Description Auditory and visual evoked potential experiments will search for significant differences in peak amplitude and latency of MMNs in persons with Down syndrome in relation to typically developing persons without Down syndrome, and in participants with Down syndrome before and after memantine treatment. As of this report date, the analysis of this exploratory measure has not yet been performed.
    Time Frame baseline and 16 weeks from start of treatment

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    14. Other Pre-specified Outcome
    Title Exploratory Study of Magnetic Resonance Imaging (MRI) as Potential Biomarkers for the Severity of the Cognitive Disability Associated to Down Syndrome and for the Efficacy of the Memantine Treatment
    Description MRI studies will be to provide precise source localization for the high-density EEG recordings of evoked potentials in a subset of 30-60 participants of this trial. In addition, these experiments will also produce high resolution sagittal slice images of the hippocampus and simple connectivity data sets. We were not able to collect data from enough participants of this study to perform any meaningful statistical analysis related to this exploratory measure.
    Time Frame baseline and 16 weeks from start of treatment

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time Frame From the beginning to the end of treatment, i.e., 16-18 weeks
    Adverse Event Reporting Description The definition of adverse event and/or serious adverse event, used to collect adverse event information, does not differ from the clinicaltrials.gov definitions.
    Arm/Group Title Placebo Memantine
    Arm/Group Description 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 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)
    All Cause Mortality
    Placebo Memantine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/79 (0%) 0/81 (0%)
    Serious Adverse Events
    Placebo Memantine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/79 (0%) 0/81 (0%)
    Other (Not Including Serious) Adverse Events
    Placebo Memantine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 44/79 (55.7%) 32/81 (39.5%)
    Endocrine disorders
    Increase in thyroid-stimulating hormone levels 3/79 (3.8%) 0/81 (0%)
    Gastrointestinal disorders
    Diarrhea 4/79 (5.1%) 5/81 (6.2%)
    Nausea or vomiting 2/79 (2.5%) 3/81 (3.7%)
    General disorders
    Transient dizziness 6/79 (7.6%) 8/81 (9.9%)
    Headache 3/79 (3.8%) 3/81 (3.7%)
    Drowsiness 4/79 (5.1%) 2/81 (2.5%)
    Weakness or fatigue 1/79 (1.3%) 3/81 (3.7%)
    Insomnia 0/79 (0%) 3/81 (3.7%)
    Increased appetite 2/79 (2.5%) 0/81 (0%)
    Infections and infestations
    Signs and symptoms of upper respiratory viral infection 12/79 (15.2%) 9/81 (11.1%)
    Tonsillitis 2/79 (2.5%) 0/81 (0%)
    Herpes simplex flair-up 0/79 (0%) 1/81 (1.2%)
    Psychiatric disorders
    Anxiety 4/79 (5.1%) 6/81 (7.4%)
    Mood changes or irritability 5/79 (6.3%) 2/81 (2.5%)
    Mood changes or sadness 3/79 (3.8%) 3/81 (3.7%)
    Oppositional or aggressive behavior 2/79 (2.5%) 1/81 (1.2%)
    Increased self-talk 2/79 (2.5%) 0/81 (0%)
    Visual hallucinations 0/79 (0%) 1/81 (1.2%)
    Renal and urinary disorders
    Urinary incontinence 1/79 (1.3%) 1/81 (1.2%)

    Limitations/Caveats

    [Not Specified]

    More Information

    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 Melissa Stasko, JD, MA
    Organization Case Western Reserve University
    Phone 216-844-7281
    Email Melissa.Stasko@case.edu
    Responsible Party:
    Dr. Alberto Costa, MD, PhD, Professor of Pediatric Neurology, University Hospitals Cleveland Medical Center
    ClinicalTrials.gov Identifier:
    NCT02304302
    Other Study ID Numbers:
    • 121971
    First Posted:
    Dec 1, 2014
    Last Update Posted:
    Apr 5, 2022
    Last Verified:
    Apr 1, 2022