|- candidate number||3884|
|- NTR Number||NTR1448|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||28-aug-2008|
|- Secondary IDs||08-192 METC UMC Utrecht|
|- Public Title||Lithium trial in ALS|
|- Scientific Title||A randomised sequential trial of Lithium
In amyotrophic lateral sclerosis|
|- hypothesis||Lithium has important neuroprotective properties involving mechanisms that may play a role in the pathogenesis of ALS. In addition, lithium significantly prolonged the disease duration in the animal model for ALS, the SOD1 transgenic mouse as also in a small cohort of ALS patients.|
|- Healt Condition(s) or Problem(s) studied||Amyotrophic Lateral Sclerosis (ALS), Lithium|
|- 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%) ˇÝ 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.
|- 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.
* Renal failure. Severe cardiac diseases. Brain damage. Addison disease. Hypothyroidism unresponsive to thyroid hormone suppletion. Precaution in patients with a (possibly) disturbed sodiumbalance like in extreme perspiration and sodium depleted diet.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-okt-2008|
|- planned closingdate||30-sep-2010|
|- Target number of participants||191|
|- Interventions||ALS patients included in the trial are treated with either Lithiumcarbonate (plasma level 0,4-0,8mmol/l) or placebo. The duration of follow-up is maximal 2 years or untill a clinical endpoint is reached.|
|- Primary outcome||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.
|- Secondary outcome||- The rate of decline in daily functioning:|
The “ALS Functional Rating Scale” (ALSFRS-R) is an easily applicable questionnaire, to assess the opinion of the patient regarding his/her own possibilities and/or dependency in the activities of daily living. The rate of decline of the ALSFRS-R will be measured from inclusion to the clinical endpoint.
|- Timepoints||Sequential analysis|
|- Trial web site||http://www.juliuscenter.com/LITRA |
|- status||stopped: trial finished|
|- CONTACT FOR PUBLIC QUERIES||trial nurse I. Beilen, van|
|- CONTACT for SCIENTIFIC QUERIES||Drs. E. Verstraete|
|- Sponsor/Initiator ||University Medical Center Utrecht (UMCU), Department of Neurology|
(Source(s) of Monetary or Material Support)
|University Medical Center Utrecht (UMCU)|
|- Brief summary||Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with loss of motor neurons in the brain and spinal cord. A recent study has suggested a favourable effect of lithiumcarbonate on survival and disease progression. We'll perform a randomised sequential trial of Lithiumcarbonate versus placebo in ALS. Survival is the primary outcome measure and daily functioning is a secondary outcome measure. |
|- Main changes (audit trail)|
|- RECORD||28-aug-2008 - 19-jun-2011|