E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
No medical condition is under investigation. The project investigates normal age-related decline in intellectual abilities.
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E.1.1.1 | Medical condition in easily understood language |
No medical condition is under investigation. The project investigates normal age-related decline in intellectual abilities. |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Behavioral Disciplines and Activities [F04] |
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 |
To investigate effects of enhanced dopaminergic neurotransmission on efficiency of working memory training for improving fluid intelligence (reasoning). |
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E.2.2 | Secondary objectives of the trial |
To study effects of enhanced dopaminergic neurotransmission on efficiency of working memory training for improving episodic memory, creativity, switching and updating performance.
To study effects of dopamine-enhanced working memory training on structural and functional brain connectivity.
To investigate effects of dopamine-enhanced working memory training on plasma and CSF markers of brain plasticity (e.g. BDNF), dopamine metabolism (e.g. homovanillic acid, monoamine oxidase) and neurodegeneration (e.g. tau, p-tau, Abeta). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Mini-Mental State Examination score >26;
• Aged between 65 and 75 years;
• Absence of medical or psychiatric conditions specified in the exclusion criteria;
• Signed informed consent;
• Right handedness;
• Fluent Swedish;
• Absence of colorblindness;
• No previous participation in studies of similar design;
• No trauma to the head with loss of consciousness for more than 10 min;
• No history of brain injuries;
• No hormonal imbalance diseases (e.g. Cushing’s syndrome);
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E.4 | Principal exclusion criteria |
• Glaucoma (any history);
• Any history of serious heart disease (myocardial infarction, arrhythmia, atrioventricular block);
• Serious problems with heart and blood vessels, systolic/diastolic blood pressure < 100/50 or >160/95; Heart Failure: NYHA > IB; Chronic Venous Disease CEAP > C2);
• Severe pulmonary diseases;
• Type I diabetes;
• Recent history (5 years) of stomach and duodenum ulcers;
• Liver diseases (e.g. hepatitis, liver failure);
• Bleeding of the stomach or intestines;
• Kidney diseases;
• Serious urination problems;
• Recent history (5 years) of malignant tumor or mole, melanoma;
• Major psychiatric disorders such as major depression, bipolar affective disorder, psychosis (risks of exacerbation of psychiatric symptoms). History of mild to moderate depression/anxiety is allowed (but not recent: 5 year cut-off);
• Patients with neurological (Parkinson's and other movement disorders, Alzheimer's disease, epilepsy) disorders will also be excluded, as the present project targets healthy elderly population;
• MRI contra-indications: metal body implants and pacemakers, cochlear implants, claustrophobia, weight over 120 kg;
• Hypersensitivity to pro-dopaminergic drugs;
• Hypersensitivity to citrus fruits/ascorbic acid;
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E.5 End points |
E.5.1 | Primary end point(s) |
Fluid intelligence defined by multi-test latent composite scores as follows:
- Spatial Intelligence (BETA-III, WASI-II, Raven's matrices)
- Verbal Intelligence (BIS analogies, Syllogisms, ETS Kit inference)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
During week 8 (visits 29-33) and week 35 (visits 36-40), compared to baseline week 2 (visits 3-7). |
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E.5.2 | Secondary end point(s) |
1. Multi-test latent composite scores of performance on tasks measuring episodic memory, creativity, switching and updating performance.
2. Functional (measured with functional magnetic resonance imaging) and structural (measured with diffusion-tensor imaging) connectivity within the fronto-parietal and fronto-subcortical circuits and cortical thickness within the fronto-parietal network.
3. Plasma and CSF markers of plasticity (e.g. DNF), dopamine metabolism (e.g. homovanillic acid, monoamine oxidase) and neurodegeneration (e.g.tau, p-tau, Abeta). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. During week 8 (visits 29-33) and week 35 (visits 36-40), compared to baseline week 2 (visits 3-7).
2. During week 9 (visit 34), compared to baseline week 3 (visit 8).
3. Plasma levels will be evaluated during week 7 (visit 28), compared to baseline week 4 (visit 9). CSF levels will be evaluated during week 9 (visit 35). |
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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 | Yes |
E.6.6 | Pharmacokinetic | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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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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 | 6 |
E.8.9.1 | In the Member State concerned days | |