E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cognitive decline and dementia in Down's syndrome |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Clinical:
• To determine the clinical efficacy of Memantine versus placebo in preventing cognitive decline in people with Down's syndrome (DS).
• To compare the safety and tolerability of Memantine versus placebo in people with DS.
Biochemical and pathological:
• To examine the ability of Memantine to alter markers of disease progression in DS patients.
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E.2.2 | Secondary objectives of the trial |
Clinical:
• To determine whether Memantine has, as compared with placebo, a significant positive impact on:
- level of independent functioning as measured by the carer-rated adaptive behavioural scale, (ABS) in adults with DS; - quality of life in adults with DS as measured by the Quality of Life questionnaire for Alzheimer's disease.
Biochemical and pathological:
• To investigate putative markers of Memantine’s mechanism of action in peripheral blood samples from living patients with DS.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Inclusion criteria will be:
1. Participants with learning disabilities due to Down’s syndrome (DS) confirmed by karyotype. A clinical diagnosis (provided by the participant’s General Practitioner or hospital Specialist) will be accepted if karyotype is not known and participant does not agree to have it tested, 2. age >40 years or any age if a diagnoses of dementia is established, 3. in participants with dementia, the diagnosis will be consistent with the 10th version of the International Classification of Diseases (ICD-10) (WHO, 1992) diagnostic criteria. 4. level of speech and comprehension of verbal commands are sufficient to understand and to answer simple requests, 5. resident in care facility or community living with a carer who is willing to accept responsibility for supervising the treatment and provide input to efficacy parameters in accordance to protocol requirements, 6. not receiving treatment with Memantine or in past 4 weeks and responsible clinician not considering treatment with Memantine, 7. participant willing to take part in study and carer with capacity willing to assent to study and in agreement for participant to take part if participant is also willing
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E.4 | Principal exclusion criteria |
Exclusion criteria will be:
1. Participants known to have sensitivity to memantine, 2. severe, unstable or uncontrolled medical or psychiatric conditions apparent from history, physical examination or investigations, 3. a current diagnosis of primary neurodegenerative disorders other than dementia such as Parkinson’s disease, Huntington’s disease, etc, 4. uncontrolled epilepsy 5. presence of challenging behaviour likely to preclude the participation during testing, 6. presence of severe motor or sensory impairment (severe deafness or blindness) that rendered the participant as untestable with the battery of tests used in the study, 7. current evidence of delirium, 8. severe renal impairment 9. low probability of treatment compliance 10. previous evidence of lack of efficacy or tolerability to Memantine 11. taking any of the following substances: • an investigational drug during the 4 weeks prior to randomization • a drug known to cause major organ system toxicity during the 4 weeks prior to randomization, • started any new psychotropic during the 4 weeks prior to randomization, • participants who had been on a stable dose of psychotropic during the 4 weeks prior to randomization are still eligible, • Memantine during the 6 weeks prior to randomization, • medication for Parkinson’s disease during randomization (dopamine agonists, selegiline) • other N-methyl-D-aspartate (NMDA) antagonists: amantadine, ketamine, and dextromethorphan • barbiturates and primidone • baclofen and dantrolen • dextrmethorphan • antimuscarinics
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E.5 End points |
E.5.1 | Primary end point(s) |
Comparing Memantine to placebo: Changes in performance from baseline on a neuropsychological battery of tests for people with DS focussing upon 3 cognitive areas: attention, memory and executive function (the DAME, battery) .
Changes in performance from baseline on an informant based questionnaire on level of independent functioning for every day tasks, the Adaptive Behavioural Scale (ABS).
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Information not present in EudraCT |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The last visit of the last subject undergoing the trial |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |