Colchicine Effect on Amyotrophic Lateral Sclerosis Patients

NCT07813858 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: CO-ALSII
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 5

Brief Summary

The goal of this clinical trial is to evaluate whether low-dose colchicine can slow disease progression in patients with amyotrophic lateral sclerosis (ALS), a progressive and fatal neurodegenerative disorder affecting motor neurons. The study is designed to answer whether patients receiving colchicine show a slower decline in functional status, as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R), over a 30-week double-blind treatment period compared to patients receiving placebo. Additional questions include whether colchicine has an effect on respiratory function, disability progression, quality of life, and overall survival. Researchers will compare participants receiving colchicine at a dose of 0.005 mg/kg/day with those receiving placebo, both in addition to standard-of-care therapy with riluzole, to assess potential differences in disease progression. Participants will be randomly assigned in a 2:1 ratio to colchicine or placebo. They will take the assigned study medication for 30 weeks during a double-blind phase and then continue into a 36-week open-label extension phase, during which all participants will receive colchicine while remaining blinded to their initial treatment assignment. Throughout the study, participants will undergo regular clinical evaluations, including assessments of motor and respiratory function, functional disability, and quality of life, for a total follow-up period of up to 66 weeks. Blood samples will also be collected to investigate biological markers of neurodegeneration and inflammation.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Amyotrophic Lateral Sclerosis; Colchicine; ALSFRS-R; TDP-43; Randomized Controlled Trial; Disease progression; survival

Outcome Measures

Primary Outcomes (1)

• Changes in ALS disease progression as measured by ALS Functional rating Scale Revised (ALSFRS-R)

  To assess whether low-dose colchicine slows disease progression in ALS by comparing the monthly rate of decline in the ALS Functional Rating Scale-Revised (ALSFRS-R) total score between the colchicine and placebo groups during the double-blind treatment phase.

  Baseline to Week 30 (double-blind treatment period)

Secondary Outcomes (13)

• Longitudinal change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score

  Baseline to Weeks 4, 8, 12, 18, 24, 30, 42, 54, and 66

• Change in ROADS score

  Baseline to Weeks 8, 18, 30, 42, 54, and 66

• Tracheostomy-free survival rate

  From randomization to Week 66

• Change in Forced Vital Capacity (FVC)

  Baseline to Weeks 8, 18, 30, 42, 54, and 66

• Change in Amyotrophic Lateral Sclerosis Assessment Questionnaire-40 (ALSAQ-40) score

  Baseline to 30, and 66

Study Arms (2)

Colchicine 0.005 mg/kg/day + Riluzole 100 mg

ACTIVE COMPARATOR

Oral colchicine will be administered at fast, at specified dose pro kilograms for 30 weeks, while taking Riluzole 100 mg/day

Drug: Colchicine 0.5 MG Oral Tablet

Placebo + Riluzole 100 mg

PLACEBO COMPARATOR

Placebo pills will be administered at fast, while taking Riluzole 100 mg/day

Drug: Placebo Oral Tablet

Interventions

Colchicine 0.5 MG Oral Tablet DRUG

Low-dose colchicine administered orally at 0.005 mg/kg/day as an add-on to standard-of-care therapy with riluzole. Participants receive colchicine once daily or every other day depending on body weight (≥70 kg: 0.5 mg daily; \<70 kg: 0.5 mg every other day) using matching oral tablets. The intervention is administered during a 30-week double-blind phase followed by a 36-week open-label extension phase.

Colchicine 0.005 mg/kg/day + Riluzole 100 mg

Placebo Oral Tablet DRUG

Matching placebo oral tablets identical in appearance, taste, and administration schedule to colchicine. Participants receive placebo in addition to standard-of-care therapy with riluzole. The placebo is administered orally once daily or every other day depending on body weight, following the same dosing schedule as the active treatment arm, during the 30-week double-blind phase. Participants subsequently enter a 36-week open-label extension phase during which all participants receive active colchicine.

Placebo + Riluzole 100 mg

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient age strictly between 18 and 80 years at the time of screening.
• Definitively established diagnosis of ALS (sporadic or familial) matching standardized clinical consensus parameters.
• Stable background regimen of European gold-standard Riluzole therapy maintained at a fixed dose of 100 mg/day for a minimum of 1 month prior to baseline randomization.
• BMI\>17.5 Kg/m2
• Sufficient respiratory capability, verified by an upright Forced Vital Capacity (FVC) \>= 70% of predicted normal values at screening (highest value of three sequential tests).
• Patient must display full cognitive and communicative capacity to provide written, personally signed Independent Ethics Committee-approved Informed Consent prior to initiation of any protocolized procedures.
• Use of highly effective contraception both for males and females

You may not qualify if:

• Concurrent participation or treatment within any other interventional or drug-based clinical trial.
• Clinically significant hepatic impairment (defined as baseline serum transaminases AST or ALT exceeding 3x Upper Limit of Normal \[ULN\], or total bilirubin exceeding 2x ULN).
• Severe renal insufficiency, documented bone marrow suppression, or significant hematological abnormalities.
• Known hypersensitivity or systemic intolerance to colchicine or any of the manufacturing excipients (lactose, sucrose, magnesium stearate, arabic gum).
• Pregnancy, active lactation, or unwillingness of fertile male/female subjects to strictly comply with highly effective double-barrier contraception regimens throughout the study and for 100 days post-final dose.

Sponsors & Collaborators

• Azienda Ospedaliero-Universitaria di Modena: lead
• University of Milan: collaborator
• Istituto Di Ricerche Farmacologiche Mario Negri: collaborator

Study Sites (5)

Centro Clinico Nemo

Milan, Milano, 20162, Italy

Location

CENTRO SLA, Ospedale Civile di Baggiovara, AOU Modena

Modena, Modena, 41126, Italy

Location

CENTRO SLA, AOU Università Degli Studi Della Campania Luigi Vanvitelli

Naples, Napoli, 80131, Italy

Location

CENTRO SLA, AOU Maggiore Della Carità

Novara, Novara, 28100, Italy

Location

CENTRO SLA, Fondazione Istituto Neurologico Nazionale Casimiro Mondino IRCCS

Pavia, Pavia, 27100, Italy

Location

Related Publications (2)

• Mandrioli J, Crippa V, Cereda C, Bonetto V, Zucchi E, Gessani A, Ceroni M, Chio A, D'Amico R, Monsurro MR, Riva N, Sabatelli M, Silani V, Simone IL, Soraru G, Provenzani A, D'Agostino VG, Carra S, Poletti A. Proteostasis and ALS: protocol for a phase II, randomised, double-blind, placebo-controlled, multicentre clinical trial for colchicine in ALS (Co-ALS). BMJ Open. 2019 May 30;9(5):e028486. doi: 10.1136/bmjopen-2018-028486.

  PMID: 31152038 BACKGROUND

• Gianferrari G, Cuoghi Costantini R, Crippa V, Carra S, Bonetto V, Pansarasa O, Cereda C, Zucchi E, Martinelli I, Simonini C, Vicini R, Fini N, Trojsi F, Passaniti C, Ticozzi N, Doretti A, Diamanti L, Fiamingo G, Conte A, Dalla Bella E, D'Errico E, Scarian E, Pasetto L, Antoniani F, Galli V, Casarotto E; Co-ALS Investigators Group; D'Amico R, Poletti A, Mandrioli J. Colchicine treatment in amyotrophic lateral sclerosis: safety, biological and clinical effects in a randomized clinical trial. Brain Commun. 2024 Sep 5;6(5):fcae304. doi: 10.1093/braincomms/fcae304. eCollection 2024.

  PMID: 39291166 BACKGROUND

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Disease Progression

Interventions

Colchicine; Tablets

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Giulia Gianferrari, MD

  Azienda Ospedaliero-Universitaria di Modena

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Giulia Gianferrari, MD

CONTACT

059-3961640; gianferrari.giulia@aou.mo.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: placebo will be unrecognizable from active treatment (both in tablets)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: sponsor-investigator

Model Details: Participants are randomized 2:1 to colchicine or placebo in a double-blind, parallel-group design, followed by an open-label extension phase in which all participants receive colchicine.

Study Record Dates

• First Submitted: September 2, 2026
• First Posted: September 10, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: September 10, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: The data will become available at study completion (after final data analysis)
• Access Criteria: specific personal request by the subject

Locations

IT (5)