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.
ID
Source
Brief title
Condition
- Neuromuscular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome measure is 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
A secundary study parameter is the rate of decline in daily functioning and the
occurrence of adverse effects and events.
Background summary
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with loss of
motor neurons in the brain and spinal cord. The disease is characterized by
progressive muscle weakness. The median survival is 3 years. 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. A recent study on ALS-mice and a small
cohort of patients (n=44) has shown a favourable effect of lithium on disease
progression and survival.
Study objective
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.
Study design
Double-blind placebo controled trial with sequential analysis.
Intervention
One group is treated with lithiumcarbonate, the dosage depending on the plasma
level (0,4-0,8mmol/l). The other group receives a placebo (at random dosage).
Study burden and risks
Patients who participate in the study should visit the outpatient clinic five
times the first year, afterwards follow-up by telephone can take place. In the
beginning frequent control of lithium plasma levels should be performed
(approximately weekly). As soon as the patient is adequately established on the
medication, the controls can be reduced untill two times a year (together with
riluzol controls). Lithium can cause adverse effects and there is a risk for
toxicity to occur. Considering the theoretical and clinical support for the
hypothesis that lithium is effective in ALS we think it compensates for the
risks. By means of profound planning of the study we aim at maximal risk
reduction.
Heidelberglaan 100
3584CX Utrecht
NL
Heidelberglaan 100
3584CX Utrecht
NL
Listed location countries
Age
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.
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.
*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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2008-002110-22-NL |
| CCMO | NL22827.041.08 |
| OMON | NL-OMON20046 |