NCT03693781

Colchicine for Amyotrophic Lateral Sclerosis

Colchicine for Amyotrophic Lateral Sclerosis: a Phase II, Randomized, Double Blind, Placebo Controlled, Multicenter Clinical Trial

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 54 (actual)
• Sponsor: Azienda Ospedaliero-Universitaria di Modena · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

The study evaluates the effects of two different Colchicine doses (0.01mg/kg/day or 0.005 mg/kg/day) compared to placebo in Amyotrophic Lateral Sclerosis (ALS) patients. Disease progression as defined by changes in ALSFRS-r is the primary outcome measure. Other measures of clinical progression and survival, together with safety and tolerability of Colchicine in ALS patients will be assessed.

Detailed description

Recent evidence supports the disruption of the ubiquitin-proteasome-system and autophagy as central events in ALS. ALS is characterized by the presence of misfolded proteins prone to oligomerize into aggregates, which exert a toxic effect by affecting several intracellular functions. Heat shock protein B8 (HSPB8) recognizes and promotes the autophagy-mediated removal of misfolded mutant SOD1 and TDP-43 fragments from ALS motor neurons (MNs). Moreover, HSPB8-BAG3-HSP70 maintains the so called "granulostasis", a surveillance mechanism that avoids the conversion of dynamic stress granules (SGs) into aggregation-prone assemblies, which are a hallmark of ALS. Colchicine enhances the expression of HSPB8 and of several autophagy players while blocking TDP-43 accumulation in neurons. Moreover, given the cross-talk between infalmmation and autophagy, the well-known antinflammatory action of Cochicine may contribute to cell homeostasis. Based on these premises, this is a phase II randomized, double-blind, placebo-controlled, multicenter (9 MND Centres in Italy: 2 centres in Milan, Pavia, Turin, Modena, Padua, Rome, Naples, Bari), clinical trial to test efficacy of Colchicine in ALS.

Conditions

• Amyotrophic Lateral Sclerosis

Interventions

Type	Name	Description
DRUG	Colchicine 1 MG Oral Tablet	Colchicine tablets depending on arm (0.01 mg/kg/day, 0.005 mg/kg/day, placebo) and on weight (\>70 kg or \<71 kg) for 30 weeks of duration.
DRUG	Colchicine 1 MG Oral Tablet	Colchicine tablets depending on arm (0.01 mg/kg/day, 0.005 mg/kg/day, placebo) and on weight (\>70 kg or \<71 kg) for 30 weeks of duration.
DRUG	Placebo Oral Tablet	Corresponding tablets for 30 weeks

Timeline

• Start date: 2019-04-10
• Primary completion: 2022-04-14
• Completion: 2023-01-03
• First posted: 2018-10-03
• Last updated: 2023-03-01

Locations

8 sites across 1 country: Italy