Tideglusib for the Treatment of Amyotrophic Lateral Sclerosis (TIDALS): a Randomized Placebo-controlled Phase II Trial
Overview
- Phase
- Phase 2
- Intervention
- Tideglusib
- Conditions
- Amyotrophic Lateral Sclerosis
- Sponsor
- University of Zurich
- Enrollment
- 98
- Locations
- 5
- Primary Endpoint
- Increase in Alanine Aminotransferase
- Status
- Not yet recruiting
- Last Updated
- last year
Overview
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.
Investigators
Eligibility Criteria
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)
Arms & Interventions
Tideglusib
Patients receive 1000 mg Tideglusib once daily per os
Intervention: Tideglusib
Placebo
Patients receive placebo matching Tideglusib 100 mg once daily per os
Intervention: Tideglusib
Outcomes
Primary Outcomes
Increase in Alanine Aminotransferase
Time Frame: 14 weeks
Increase in Alanine Aminotransferase \< 3x of Upper Limit of Normal
Secondary Outcomes
- Most common side effect(14 weeks)