Amyotrophic Lateral Sclerosis
Conditions
Brief summary
Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative condition, mainly characterized by progressive weakness and wasting of the limbs, the respiratory and bulbar muscles. Respiratory insufficiency leads to a fatal outcome after a mean diseases duration of only three to five years. The disease is characterized by pathological accumulations of a protein called TDP-43, which can be found large cortical and sub-cortical areas of post-mortem ALS brains. No causal treatment for this condition is known to date, and there is a large unmet need to develop new strategies in order to halt or slow down its progression. The aim of this study is to test the safety and tolerability of Tideglusib, a treatment that is already in clinical trials for other neuromuscular conditions, in patients with ALS. It is assumed that this drug may have a significant therapeutic benefit in this population due to his mode of action: In the ALS mouse model, Tideglusib decreases significantly the amount of accumulated TDP-43 proteins within the cells.
Interventions
DRUGTideglusib
1000 mg/day per os
Sponsors
University of Lausanne Hospitals
University of Bern
Cantonal Hospital of St. Gallen
University Hospital, Geneva
University of Zurich
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Possible, probable (clinically or laboratory supported) or definite ALS according to the revised version of the El Escorial criteria * Disease duration \< 18 months * Vital capacity of more than 60% of normal (defined as slow vital capacity, best of three measurements) * Age more than 18 years * On a stable dose of riluzole for at least four weeks or not taking riluzole * On a stable dose of edaravone for at least four weeks or not taking edaravone * Capable of thoroughly understanding all information given and giving full informed consent according to GCP
Exclusion criteria
* Previous participation in another clinical study within the preceding 12 weeks * Proven SOD1- or FUS - mutation * Tracheostomy or assisted ventilation of any type during the preceding three months * Pregnancy or breast-feeding females * Any medical condition known to have an association with motor neuron dysfunction which might confound or obscure the diagnosis of ALS * Presence of any concomitant life-threatening disease or impairment likely to interfere with functional assessment * Evidence of a major psychiatric disorder or clinically evident dementia precluding evaluation of symptoms * Alcoholism * Cardiovascular disorder/arrhythmia * Impaired kidney function, defined as creatinine levels of 2.5 x upper limit of normal (ULN) * Impaired liver function, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) of 3 x ULN * Liable to be not cooperative or comply with trial requirements as assessed by the investigator, or unable to be reached in the case of emergency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Increase in Alanine Aminotransferase | 14 weeks | Increase in Alanine Aminotransferase \< 3x of Upper Limit of Normal |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Most common side effect | 14 weeks | Occurence of diarrhea in less then 18 % of patients |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory outcome: clinical efficacy | 14 weeks | Difference of decline in points on the Revised ALS Functional Rating Scale between the two study arms |
| Exploratory outcome: vital capacity | 14 weeks | slow vital capacity in % |
Countries
Switzerland
Contacts
Primary ContactAnnemarie Hübers
Outcome results
None listed