Down Syndrome Memantine Follow-up Study
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|ClinicalTrials.gov Identifier: NCT02304302|
Recruitment Status : Completed
First Posted : December 1, 2014
Last Update Posted : July 28, 2020
|Condition or disease||Intervention/treatment||Phase|
|Down Syndrome Intellectual Disability||Drug: Memantine Drug: Placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||200 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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 :||October 2014|
|Actual Primary Completion Date :||July 22, 2020|
|Actual Study Completion Date :||July 22, 2020|
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.
Identically looking placebo capsules bid (after a four-week regimen designed to mimic dose escalation protocol)
Other Name: Inactive Capsules
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.
Encapsulated Namenda 10 mg bid (after four week dose escalation protocol)
Other Name: Namenda
- Efficacy of the drug Memantine as assessed by the California Verbal Learning Test-II (CVLT-II) short form [ Time Frame: 3 years ]The primary efficacy measure is focused on episodic memory. It assesses supraspan word learning ability as an index of episodic verbal long-term memory. The choice of the appropriate measure for individuals with Down syndrome was based on results of our pilot clinical trial of the drug memantine in young adults with Down syndrome (Boada et al., 2012). We hypothesize that treatment with memantine will produce significant improvements in the CVLT-II short form. Two dependent variables were selected, based on prior literature, as indexing hippocampal function: Total number of target items correct summed across learning trials 1-4, and total free recall discriminability for the learning trials, which takes into account hits as well as false positives.
- Efficacy of the drug Memantine as assessed by Paired Associates Learning (PAL) from the Cambridge Neuropsychological Test Automated Battery (CANTAB) [ Time Frame: 3 years ]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.
- Efficacy of the drug Memantine as assessed by Recall of Digits (Differential Ability Scales; DAS-II). [ Time Frame: 3 years ]This is a measure of rote short-term verbal memory. Total number of items correct will be used as the dependent variable.
- Efficacy of the drug Memantine as assessed by Pattern Recognition Memory (PRM; part of the CANTAB) [ Time Frame: 3 years ]This is a measure of non-verbal memory. Total number correct across the two series of items presented will be used as the dependent variable.
- Efficacy of the drug Memantine as assessed by Spatial Working Memory (part of the CANTAB) [ Time Frame: 3 years ]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. Two dependent variables were selected: 1) 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; and 2) a "strategy" score, which indexes the number of times the participant started a search with a different box, the latter being an inefficient strategy (i.e., high strategy scores denote poorer performance).
- Efficacy of the drug Memantine as assessed by Spatial Span (part of the CANTAB) [ Time Frame: 3 years ]This measure is a computerized version of the Corsi Blocks task, a long-standing neuropsychological test. Two dependent variables were selected for this test: 1) span length, which is the longest sequence of numbers recalled accurately (possible score ranges from 2 to 9); and 2) total usage errors, which represents the number of times a subject selects a box no in the sequence being recalled.
- Efficacy of the drug Memantine as assessed by The Go - No Go task [ Time Frame: 3 years ]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. Two dependent variables were selected: 1) the proportion of no-go targets in which a subject fails to inhibit a response under the go-cue (pre-potent) condition; and 2) speed of response execution to Go targets.
- Safety and tolerability of the drug Memantine as assessed by the incidence of adverse events [ Time Frame: 3 years ]Incidence of adverse events will be monitored by clinical history, physical examinations, electrocardiograms (ECGs), clinical laboratory tests, and the Screen for Childhood Anxiety Related Emotional Disorders (SCARED).
- Intellectual functioning of the participants as assessed by Matrices subtest of the Differential Ability Scales-II (DAS-II) [ Time Frame: 3 years ]This test will provide 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.
- Linguistic functioning of the participants as assessed by the Test for Reception of Grammar 2nd edition (TROG-II) [ Time Frame: 3 years ]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.
- Linguistic functioning of the participants as assessed by the Peabody Picture Vocabulary Test-IV (PPVT-IV) [ Time Frame: 3 years ]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.
- Adaptive/Behavioral Functioning of the participants as assessed by the Scales of Independent Behavior-Revised (SIB-R) [ Time Frame: 3 years ]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 will be used as dependent variables.
- 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 [ Time Frame: 3 years ]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
- 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 [ Time Frame: 3 years ]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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02304302
|United States, Ohio|
|University Hospitals Case Medical Center|
|Cleveland, Ohio, United States, 44106|
|Sociedade Beneficente Israelita Brasileira Albert Einstein|
|São Paulo, SP, Brazil, 05652- 900|
|Principal Investigator:||Alberto C Costa, MD, PhD||University Hospitals Cleveland Medical Center|
|Study Director:||Stephen L Ruedrich, MD||University Hospitals Cleveland Medical Center|