E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Body processes [G] - Genetic Phenomena [G05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10013616 |
E.1.2 | Term | Down's syndrome |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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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 |
Our primary objective is to determine if brain myo-inositol concentration is significantly reduced in non-demented DS individuals by brief 4 week treatment with lithium carbonate at normal therapeutic doses with full monitoring of potential side effects in all participants. |
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E.2.2 | Secondary objectives of the trial |
Our secondary objectives are to:
• Investigate the association of clinical and biomarker measures to any changes in brain myo-inositol concentrations
• Determine whether lithium has a differential impact on different genotypes that confer additional risk of AD in DS e.g. tau haplotypes, ApoE4 and other polymorphisms that affect amyloid processing e.g. intron 7 repeat of APP
• Also look at broader range of biomarkers to determine the impact of lithium on the brains of individuals with DS, including markers of amyloid oxidative stress and systemic inflammation
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Individuals with Down Syndrome
• Over the age of 18 years
• Able to provide informed consent or have a legal representative to consent on their behalf if they lack capacity
• Able to communicate with the investigator and to comply with requirements of the study
• Has carer support
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E.4 | Principal exclusion criteria |
• Individuals with contraindications to lithium treatment
• Individuals with contraindications to undergoing a magnetic resonance scan
• Non-compliance with taking of the tablets between baseline and the 4-week assessment
• Treatment with lithium within the last 6 months
• Evidence of dementia
• Pregnancy
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E.5 End points |
E.5.1 | Primary end point(s) |
Our primary objective is to determine if brain myo-inositol concentration is significantly reduced in non-demented DS individuals by brief 4 week treatment with lithium carbonate at normal therapeutic doses with full monitoring of potential side effects in all participants |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Our secondary objectives are to:
• Investigate the association of clinical and biomarker measures to any changes in brain myo-inositol concentrations
• Determine whether lithium has a differential impact on different genotypes that confer additional risk of AD in DS e.g. tau haplotypes, ApoE4 and other polymorphisms that affect amyloid processing e.g. intron 7 repeat of APP
• Also look at broader range of biomarkers to determine the impact of lithium on the brains of individuals with DS, including markers of amyloid oxidative stress and systemic inflammation
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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 end of the trial is defined as the last patient, last visit |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |