LCU-ALS NREScommittee london bloomsburry 15/LO/0059
Research type
Research Study
Full title
Genetic post-hoc analysis of blind randomised controlled trials of Lithium Carbonate in patients with Amyotrophic Lateral Sclerosis. Is Lithium Carbonate beneficial to homozygous UNC13a ALS patients?
IRAS ID
168859
Contact name
Ammar / A. Al-Chalabi
Contact email
Sponsor organisation
King’s College London
Duration of Study in the UK
0 years, 3 months, 0 days
Research summary
Amyotrophic lateral sclerosis (ALS) is a devastating, fatal neurologic disease for which there is no effective treatment. Based on promising results in animal studies several trials with lithium in ALS were performed, but were unfortunately all negative. Recent research has shown that certain genetic variants (UNC13a and C9orf72) negatively influence survival in ALS and may thus also effect the outcome of clinical trials. Longstanding collaborators in The Netherlands have reanalyzed their lithium trial taking these genetic variants into account and their data suggests that lithium may be beneficial to patients with UNC13a variants. ALS patients with UNC13a variants treated with lithium had a mean survival of 16.9 months (SE 3.3) compared to 9.5 months (SE 1.5) for ALS patients with UNC13a variants treated with placebo. Although the Dutch data is very promising, the number of UNC13a ALS patients was relatively small and therefore a definitive conclusion could not be reached. Therefore we propose to perform a genetic post-hoc analysis on 3 lithium trials in ALS conducted in The Netherlands (LITRA), Italy (LITALS) and the UK (LiCALS).
In the UK the majority of ALS patients donate DNA samples to the MND DNA bank. These samples have all been analyzed for variants in many genes, including UNC13a and C9orf72 (prof Al-Chalabi is also chief investigator on the genetic studies). Therefore, genetic data will likely be available for the participants of the LiCALS trial. The main purpose for this application is to request permission to temporarily reverse the anonymisation in the LiCALS trial, so the genetic data can be linked to the trial data to facilitate this genetic post-hoc analysis.
The possibility that lithium could be effective in a specific group of ALS patients is very exciting and could be a huge, much needed step forward in the treatment of this detrimental disease.REC name
London - Bloomsbury Research Ethics Committee
REC reference
15/LO/0059
Date of REC Opinion
11 Feb 2015
REC opinion
Favourable Opinion