Tideglusib for the Treatment of Amyotrophic Lateral Sclerosis (TIDALS)

Tideglusib for the Treatment of Amyotrophic Lateral Sclerosis (TIDALS): a Randomized Placebo-controlled Phase II Trial

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: Tideglusib

• Study Type: Interventional
• Enrollment (Estimated): 98
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Annemarie Hübers; Phone Number: 0795531171; Email: annemarie.hubers@hcuge.ch

Study Locations

• Switzerland
  • Bern, Switzerland
    • University Hospital Bern
    • Contact: Olivier Scheidegger
  • Genève, Switzerland, 1205
    • University Hospital Geneva
    • Contact: Annemarie Hübers; Phone Number: 0795531171; Email: annemarie.hubers@hcuge.ch
  • Lausanne, Switzerland
    • University Hospital Lausanne
    • Contact: David Benninger
  • Saint-Gall, Switzerland
    • Kantonsspital St. Gallen
    • Contact: Markus Weber
  • Zürich, Switzerland
    • University Hospital Zurich
    • Contact: Hans Jung

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Increase in Alanine Aminotransferase	Increase in Alanine Aminotransferase < 3x of Upper Limit of Normal	14 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Most common side effect	Occurence of diarrhea in less then 18 % of patients	14 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory outcome: clinical efficacy	Difference of decline in points on the Revised ALS Functional Rating Scale between the two study arms	14 weeks
Exploratory outcome: vital capacity	slow vital capacity in %	14 weeks

Collaborators and Investigators

• Sponsor: University of Zurich
• Collaborators: University Hospital, Geneva; University of Lausanne Hospitals; University of Bern; Cantonal Hospital of St. Gallen
• Investigators: Principal Investigator: Annemarie Hübers, University Hospital, Geneva

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2025
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: October 4, 2021
• First Submitted That Met QC Criteria: October 24, 2021
• First Posted (Actual): November 3, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 24, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: TIDALS_01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No