TIDALS: Tideglusib for the Treatment of Amyotrophic Lateral Sclerosis
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Tideglusib Patients receive 1000 mg Tideglusib once daily per os |
Drug: Tideglusib
1000 mg/day per os
|
| Placebo Comparator: Placebo Patients receive placebo matching Tideglusib 100 mg once daily per os |
Drug: Tideglusib
1000 mg/day per os
|
Outcome Measures
Primary Outcome Measures
- Increase in Alanine Aminotransferase [14 weeks]
Increase in Alanine Aminotransferase < 3x of Upper Limit of Normal
Secondary Outcome Measures
- Most common side effect [14 weeks]
Occurence of diarrhea in less then 18 % of patients
Other Outcome Measures
- 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 %
Eligibility Criteria
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
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Any medical condition known to have an association with motor neuron dysfunction which might confound or obscure the diagnosis of ALS
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospital Bern | Bern | Switzerland | ||
| 2 | University Hospital Geneva | Genève | Switzerland | 1205 | |
| 3 | University Hospital Lausanne | Lausanne | Switzerland | ||
| 4 | Kantonsspital St. Gallen | Saint-Gall | Switzerland | ||
| 5 | University Hospital Zurich | Zürich | Switzerland |
Sponsors and Collaborators
- University Hospital, Geneva
- University of Lausanne Hospitals
- University of Zurich
- University of Bern
- Cantonal Hospital of St. Gallen
Investigators
- Principal Investigator: Annemarie Hübers, University Hospital, Geneva
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TIDALS_01