Clinical trial NCT05105958: Tideglusib for the Treatment of Amyotrophic Lateral Sclerosis
Official title: Tideglusib for the Treatment of Amyotrophic Lateral Sclerosis (TIDALS): a Randomized Placebo-controlled Phase II Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Lead sponsor: University of Zurich
Sponsor class: OTHER
Collaborators: name: University of Lausanne Hospitals
name: University of Bern
name: Cantonal Hospital of St. Gallen
name: University Hospital, Geneva
First posted: 2021-11-03
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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)
* 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

Primary outcomes:
measure: Increase in Alanine Aminotransferase
timeFrame: 14 weeks
Secondary outcomes:
measure: Most common side effect
timeFrame: 14 weeks
Other outcomes:
measure: Exploratory outcome: clinical efficacy
timeFrame: 14 weeks
measure: Exploratory outcome: vital capacity
timeFrame: 14 weeks
Locations:
city: Bern
country: Switzerland
facility: University Hospital Bern
city: Genève
country: Switzerland
facility: University Hospital Geneva
city: Lausanne
country: Switzerland
facility: University Hospital Lausanne
city: Saint-Gall
country: Switzerland
facility: Kantonsspital St. Gallen
city: Zürich
country: Switzerland
facility: University Hospital Zurich
Study officials:
affiliation: University Hospital, Geneva
name: Annemarie Hübers
role: PRINCIPAL_INVESTIGATOR
References: