Down Syndrome Clinical Trial
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
NCT number | NCT02304302 |
Other study ID # | 121971 |
Secondary ID | |
Status | Completed |
Phase | Phase 2 |
First received | |
Last updated | |
Start date | October 2014 |
Est. completion date | July 22, 2020 |
Verified date | April 2022 |
Source | University Hospitals Cleveland Medical Center |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 160 |
Est. completion date | July 22, 2020 |
Est. primary completion date | July 22, 2020 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 15 Years to 32 Years |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
Brazil | Sociedade Beneficente Israelita Brasileira Albert Einstein | São Paulo | SP |
United States | University Hospitals Case Medical Center | Cleveland | Ohio |
Lead Sponsor | Collaborator |
---|---|
University Hospitals Cleveland Medical Center | Alana USA Foundation |
United States, Brazil,
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* Note: There are 61 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Intellectual Functioning of the Participants as Assessed by Change in Score on the Matrices Subtest of the Differential Ability Scales-II (DAS-II) | 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). | baseline and 16 weeks from start of treatment | |
Other | Linguistic Functioning of the Participants as Assessed by Change in Score on the Test for Reception of Grammar 2nd Edition (TROG-II) | 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. | baseline and 16 weeks from start of treatment | |
Other | Linguistic Functioning of the Participants as Assessed by Change in Score on the Peabody Picture Vocabulary Test-IV (PPVT-IV) | 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. | baseline and 16 weeks from start of treatment | |
Other | Adaptive/Behavioral Functioning of the Participants as Assessed by Change in Score on the Scales of Independent Behavior-Revised (SIB-R) | 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. | baseline and 16 weeks from start of treatment | |
Primary | 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 | 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. | baseline and 16 weeks from start of treatment | |
Secondary | 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) | 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. | baseline and 16 weeks from start of treatment | |
Secondary | Efficacy of the Drug Memantine as Assessed by Change in Score on the Recall of Digits Forward (From the Differential Ability Scales; DAS-II) | 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. | baseline and 16 weeks from start of treatment | |
Secondary | 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) | 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. | baseline and 16 weeks from start of treatment | |
Secondary | 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) | 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). | baseline and 16 weeks from start of treatment | |
Secondary | Efficacy of the Drug Memantine as Assessed by Change in Score on the Spatial Span (Part of the Cambridge Neuropsychological Test Automated Battery -- CANTAB) | 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). | baseline and 16 weeks from start of treatment | |
Secondary | Efficacy of the Drug Memantine as Assessed by Change in Score on the The Go - No Go Task | 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). | baseline and 16 weeks from start of treatment | |
Secondary | Safety and Tolerability of the Drug Memantine as Assessed by Change in QTc Interval | 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. | baseline and 16 weeks from start of treatment |
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