E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Amyotrophic lateral sclerosis (ALS) is a disease characterised by progressive degeneration of motor neurons in brain and spinal cord leading to muscle weakness. ALS can occur at anytime in adulthood. Muscle weakness gradually progresses. Approximately 50% of patients die within 3 years after onset of symptoms, usually as the result of respiratory failure. To date, only one drug, i.e. riluzole, has proven to extend survival in patients with ALS, but only by approximately 3 to 6 months. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052889 |
E.1.2 | Term | ALS |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the effect of lithium treatment (plasma levels between 0,4-0,8 mEq/liter) versus placebo - in addition to riluzole 2dd 50 mg - on reaching a clinical endpoint in patients with ALS. |
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E.2.2 | Secondary objectives of the trial |
Investigate the rate of decline in daily functioning of ALS patients treated with lithium versus placebo. Get insight in the adverse effects and reactions due to lithium treatment compared to placebo in ALS patients. Gain insight in the working mechanism of lithium. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Definite, probable, or probable-laboratory supported ALS according to the revised El Escorial World Federation of Neurology criteria. 2. Intake of riluzole 2dd 50 mg 3. A disease duration (at inclusion) of more than 6 months and less than 36 months (disease onset is defined as the date of first symptoms excluding muscle cramps and fasciculations) 4. Vital capacity (VC%) ≥ 70 % of normal value (slow expiration, best of a minimum of three and a maximum of five measurements, with a respiratory function validly assessable and spontaneous, non-assisted ventilation) 5. Age 18 - 85 years (inclusive) 6. Capable of thoroughly understanding the trial information given; has signed the informed consent.
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E.4 | Principal exclusion criteria |
1. Tracheostomy, tracheostomal ventilation of any type, non-invasive ventilation more than 16 hours/ day, or supplemental oxygen during the last three months prior to inclusion. 2. Any medical condition or intoxication known to have an association with motor neuron dysfunction, which might confound or obscure the diagnosis of ALS. 3. Presence of any concomitant life-threatening disease or any disease or impairment likely to interfere with functional assessment. 4. Contra-indications for lithium therapy 5. Interaction of lithium with other medication (like NSAID’s and thiazide diuretics) that increase the chance of intoxication.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary outcome measure: Survival Survival is defined as the time from inclusion to reaching a clinical endpoint. A clinical endpoint is reached when death, tracheostomy, permanent assisted ventilation (PAV) or non-invasive ventilation (NIV) for over 16 hours occurs. Permanent assisted ventilation is defined as intubation with artificial ventilation ultimately leading to tracheostomy or death.
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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 | Yes |
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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 | 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.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
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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When the sequential analysis indicates that a boundary has been crossed, the data and safety monitoring board (DSMB) meet and decide whether or not to stop the trial. Depending on the outcome, patients will receive lithium open label or administration of trial medication will be stopped. When the interim safety analysis indicates that serious adverse effects occur significantly more often one group than in the other group, the DSMB will meet and decide whether or not to stop 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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |