Amyotrophic Lateral SclerosisPhase 2CO-ALSIINCT07813858
Colchicine Effect on Amyotrophic Lateral Sclerosis Patients
A Phase 2 study testing Colchicine 0.5 MG Oral Tablet in people with Amyotrophic Lateral Sclerosis, run by Azienda Ospedaliero-Universitaria di Modena at 5 sites in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- Colchicine 0.5 MG Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 87 participants
- Where
- 5 sitesItaly
- Study dates
- Oct 2026to Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
Italy5 sites
Centro Clinico Nemo
Milan, Milano, 20162
Federica Cerri, 02 9143371 ext. +39, federica.cerri@centrocliniconemo.it
CENTRO SLA, Ospedale Civile di Baggiovara, AOU Modena
Modena, Modena, 41126
Giulia Gianferrarri, 0593961640 ext. +39, gianferrari.giulia@aou.mo.it
CENTRO SLA, AOU Università Degli Studi Della Campania Luigi Vanvitelli
Naples, Napoli, 80131
Francesca Trojsi, 081 566 5659 ext. +39, francesca.trojsi@unicampania.it
CENTRO SLA, AOU Maggiore Della Carità
Novara, Novara, 28100
Fabiola De Marchi, 0321 3733962 ext. +39, ambulatorio.sla@maggioreosp.novara.it
CENTRO SLA, Fondazione Istituto Neurologico Nazionale Casimiro Mondino IRCCS
Pavia, Pavia, 27100
Luca Diamanti, 0382 380 225 ext. +39, luca.diamanti@mondino.it
About this study
Official title: A Randomized, Placebo-controlled, Multicenter, Clinical Trial of Colchicine in Amyotrophic Lateral Sclerosis
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.
Read more
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.
Read the detailed description
Co-ALS II is a Phase II, randomized, double-blind, placebo-controlled, multicenter clinical trial conducted in specialized ALS referral centers in Italy. The study investigates whether low-dose colchicine (0.005 mg/kg/day) can slow disease progression in patients with Amyotrophic Lateral Sclerosis (ALS), a rapidly progressive neurodegenerative disorder affecting upper and lower motor neurons.
The study is based on emerging evidence supporting a role for impaired proteostasis and neuroinflammation in ALS pathogenesis. In particular, intracellular accumulation of TDP-43 protein aggregates and dysfunction of autophagy-related pathways represent key pathogenic mechanisms. Preclinical data suggest that colchicine may enhance proteostasis mechanisms, including autophagy-related signaling pathways (e.g., TFEB, p62, LC3, and HSPB8), potentially facilitating clearance of toxic protein aggregates.
This hypothesis is further supported by findings from a previous exploratory Phase II study (Co-ALS), which suggested a potential slowing of ALSFRS-R decline with low-dose colchicine, although that study was limited by sample size and external constraints.
In Co-ALS II, 87 patients with definite or probable ALS will be randomized in a 2:1 ratio to receive colchicine or placebo in addition to standard therapy with riluzole. The study includes a screening period of up to 30 days, followed by a 30-week double-blind treatment phase and a 36-week open-label extension phase, resulting in a total follow-up of 66 weeks per participant.
The primary endpoint is the rate of decline in ALSFRS-R score over the 30-week double-blind period. Secondary endpoints include longitudinal changes in ALSFRS-R, Rasch-Built Overall ALS Disability Scale (ROADS), forced vital capacity (FVC), ALS Assessment Questionnaire-40 (ALSAQ-40), functional subdomain scores, and overall survival defined as time to death or tracheostomy.
Biological samples will be collected at baseline, week 30, and week 66 to investigate pharmacodynamic and mechanistic biomarkers. These include neurofilament light chain (NfL), TDP-43 aggregation markers in peripheral blood mononuclear cells, and circulating inflammatory mediators such as MCP-1, GFAP, and TREM2. Optional cerebrospinal fluid and skin biopsy sub-studies will further explore disease biology.
Safety will be closely monitored by an independent Data and Safety Monitoring Board (DSMB), which will periodically review unblinded safety data. Predefined stopping rules are in place for severe hematological or systemic toxicity.
Statistical analyses will compare treatment groups using longitudinal mixed-effects models and non-parametric methods as appropriate. Sample size calculations are based on observed effect sizes from the prior Co-ALS I study, with adjustment for anticipated dropout.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Colchicine 0.5 MG Oral Tablet, Placebo Oral Tablet
- Keywords
- Amyotrophic Lateral Sclerosis, Colchicine, ALSFRS-R, TDP-43, Randomized Controlled Trial, Disease progression, survival
- Medical subject headings
- Amyotrophic Lateral Sclerosis, Disease Progression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Colchicine 0.5 MG Oral TabletDrug
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.
Placebo Oral TabletDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Change in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score from baseline over time in both treatment groups. The ALSFRS-R total score ranges from 0 to 48, with higher scores indicating better functional status.
Measured: Baseline to Weeks 4, 8, 12, 18, 24, 30, 42, 54, and 66
Change in ROADS score
Change in Changes in functional disability, assessed using the Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS) score from baseline over time in both treatment groups. The ROADS score ranges from 0 to 100, with higher scores indicating better functional status.
Measured: Baseline to Weeks 8, 18, 30, 42, 54, and 66
Tracheostomy-free survival rate
Overall survival from randomization to date of death or tracheostomy
Measured: From randomization to Week 66
Change in Forced Vital Capacity (FVC)
Changes in FVC score from baseline over time in both treatment groups.
Measured: Baseline to Weeks 8, 18, 30, 42, 54, and 66
Change in Amyotrophic Lateral Sclerosis Assessment Questionnaire-40 (ALSAQ-40) score
Change in quality of life assessed using the Amyotrophic Lateral Sclerosis Assessment Questionnaire-40 (ALSAQ-40) score from baseline over time in both treatment groups. The ALSAQ-40 score ranges from 0 to 100, with higher scores indicating greater impairment and worse health-related quality of life.
Measured: Baseline to 30, and 66
Change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) domain-specific subscores
Change in domain-specific subscores of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) from baseline over time in both treatment groups, to explore differential treatment effects across functional domains. Each ALSFRS-R item is scored from 0 to 4, with higher scores indicating better functional status; domain-specific subscores (e.g., bulbar and motor domains) are calculated as the sum of the corresponding items.
Measured: Baseline to weeks 4, 8, 12, 18, 24, 30, 42, 54, and 66
Difference in monthly change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score (delta FS)
Difference in the monthly change in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score from treatment initiation to Week 30 (end of treatment), compared with the monthly change in ALSFRS-R total score from disease onset to treatment initiation. The ALSFRS-R total score ranges from 0 to 48, with higher scores indicating better functional status. For the calculation of the pre-treatment monthly change, an ALSFRS-R score of 48 is assumed at disease onset for each patient.
Measured: Onset to baseline and Baseline to weeks 30
Exploratory target-engagement objectives: Change in TDP-43 species in PBMCs
Change in autophagic clearance of TDP-43 species in peripheral blood mononuclear cells (PBMCs), assessed by measuring PBS- and RIPA-soluble and insoluble fractions, including phosphorylated forms and C-terminal fragments, from baseline to Week 30 and Week 66. Between-group mean differences will be estimated at Week 30 and Week 66.
Measured: Baseline to weeks 30, and 66
Exploratory target-engagement objectives: Change in platelet TDP-43 levels
Change in platelet TDP-43 levels, including cleaved and phosphorylated forms, from baseline to Week 30 and Week 66.
Measured: Baseline to weeks 30, and 66
Exploratory target-engagement objectives: Change in TDP-43-regulated splicing events
Change in TDP-43-regulated splicing events in POLDIP3, ATG4B, and MARK3 mRNA in whole blood from baseline to Week 30 and Week 66.
Measured: Baseline to weeks 30, and 66
Exploratory target-engagement objectives: Change in peripheral biomarker levels
Assess the effect of colchicine on peripheral biomarkers, including creatinine (mg/dL), albumin (g/dL), CRP (mg/dL), urate (mg/dL), and neurofilament light chain (NfL, pg/ml), as well as inflammatory markers (MCP1, serpinA1, TREM2, GFAP, and CHI3L1, pg/ml), measured in blood between baseline, week 30 and week 66.
Measured: Baseline to weeks 30, and 66
Exploratory target-engagement objectives: Change in cerebrospinal fluid biomarker levels
Evaluate colchicine' effects on neurodegenerative (NfL, pg/mL) and neuroinflammatory markers (MCP1, SerpinA1, TREM2, GFAP, CHI3L1 and UCHL1, pg/mL) measured in CSF between baseline and week 30 (optional for patients)
Measured: Baseline to weeks 30
Exploratory target-engagement objectives: Change in TDP-43 aggregates in skin biopsies and microvesicles
Change in TDP-43 aggregates measured in skin biopsies and microvesicles from baseline to Week 30 (optional for patients)
Measured: Baseline to weeks 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2026
- Study startOct 2026 (estimated)
- Primary completionMay 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 87 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Azienda Ospedaliero-Universitaria di Modena
- Sponsor type
- University, hospital or other
- Collaborators
- University of Milan, Istituto Di Ricerche Farmacologiche Mario Negri
- Responsible party
- Principal investigator, Giulia Gianferrari, Azienda Ospedaliero-Universitaria di Modena
- Investigators
- Giulia Gianferrari, MD, Principal investigator, Azienda Ospedaliero-Universitaria di Modena
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07813858
- Sponsor's protocol ID
- CO-ALSII
- Acronym
- CO-ALSII
- Status last verified
- Sep 2026
- First submitted
- 2 Sep 2026
- Last updated
- 10 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: de-identified individual participant data will be made available after study completion upon specific request
Publications
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.
PubMed 31152038Gianferrari 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.
PubMed 39291166
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo-controlled, Multicenter, Clinical Trial of Colchicine in Amyotrophic Lateral Sclerosis
- ClinicalTrials.gov ID
- NCT07813858
- Acronym / sponsor ID
- CO-ALSII / CO-ALSII
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- Amyotrophic Lateral Sclerosis, Colchicine, ALSFRS-R, TDP-43, Randomized Controlled Trial, Disease progression, survival
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 87 participants (estimated)
- Lead sponsor
- Azienda Ospedaliero-Universitaria di ModenaUniversity, hospital or other
- Collaborators
- University of Milan, Istituto Di Ricerche Farmacologiche Mario Negri
- Study start
- Oct 2026 (estimated)
- Primary completion
- May 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 10 Sep 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Co-ALS II is a Phase II, randomized, double-blind, placebo-controlled, multicenter clinical trial conducted in specialized ALS referral centers in Italy. The study investigates whether low-dose colchicine (0.005 mg/kg/day) can slow disease progression in patients with Amyotrophic Lateral Sclerosis (ALS), a rapidly progressive neurodegenerative disorder affecting upper and lower motor neurons.
The study is based on emerging evidence supporting a role for impaired proteostasis and neuroinflammation in ALS pathogenesis. In particular, intracellular accumulation of TDP-43 protein aggregates and dysfunction of autophagy-related pathways represent key pathogenic mechanisms. Preclinical data suggest that colchicine may enhance proteostasis mechanisms, including autophagy-related signaling pathways (e.g., TFEB, p62, LC3, and HSPB8), potentially facilitating clearance of toxic protein aggregates.
This hypothesis is further supported by findings from a previous exploratory Phase II study (Co-ALS), which suggested a potential slowing of ALSFRS-R decline with low-dose colchicine, although that study was limited by sample size and external constraints.
In Co-ALS II, 87 patients with definite or probable ALS will be randomized in a 2:1 ratio to receive colchicine or placebo in addition to standard therapy with riluzole. The study includes a screening period of up to 30 days, followed by a 30-week double-blind treatment phase and a 36-week open-label extension phase, resulting in a total follow-up of 66 weeks per participant.
The primary endpoint is the rate of decline in ALSFRS-R score over the 30-week double-blind period. Secondary endpoints include longitudinal changes in ALSFRS-R, Rasch-Built Overall ALS Disability Scale (ROADS), forced vital capacity (FVC), ALS Assessment Questionnaire-40 (ALSAQ-40), functional subdomain scores, and overall survival defined as time to death or tracheostomy.
Biological samples will be collected at baseline, week 30, and week 66 to investigate pharmacodynamic and mechanistic biomarkers. These include neurofilament light chain (NfL), TDP-43 aggregation markers in peripheral blood mononuclear cells, and circulating inflammatory mediators such as MCP-1, GFAP, and TREM2. Optional cerebrospinal fluid and skin biopsy sub-studies will further explore disease biology.
Safety will be closely monitored by an independent Data and Safety Monitoring Board (DSMB), which will periodically review unblinded safety data. Predefined stopping rules are in place for severe hematological or systemic toxicity.
Statistical analyses will compare treatment groups using longitudinal mixed-effects models and non-parametric methods as appropriate. Sample size calculations are based on observed effect sizes from the prior Co-ALS I study, with adjustment for anticipated dropout.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Colchicine 0.005 mg/kg/day + Riluzole 100 mg | Active comparator | Drug: Colchicine 0.5 MG Oral TabletOral colchicine will be administered at fast, at specified dose pro kilograms for 30 weeks, while taking Riluzole 100 mg/day |
| Placebo + Riluzole 100 mg | Placebo comparator | Drug: Placebo Oral TabletPlacebo pills will be administered at fast, while taking Riluzole 100 mg/day |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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).
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Colchicine 0.5 MG Oral TabletLow-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. | Drug | Colchicine 0.005 mg/kg/day + Riluzole 100 mg |
| Placebo Oral TabletMatching 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. | Drug | Placebo + Riluzole 100 mg |
Primary outcome
Changes in ALS disease progression as measured by ALS Functional rating Scale Revised (ALSFRS-R)
Time frame: Baseline to Week 30 (double-blind treatment period)
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.
13 secondary outcomes
Longitudinal change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score
Time frame: Baseline to Weeks 4, 8, 12, 18, 24, 30, 42, 54, and 66
Change in ROADS score
Time frame: Baseline to Weeks 8, 18, 30, 42, 54, and 66
Tracheostomy-free survival rate
Time frame: From randomization to Week 66
Change in Forced Vital Capacity (FVC)
Time frame: Baseline to Weeks 8, 18, 30, 42, 54, and 66
Change in Amyotrophic Lateral Sclerosis Assessment Questionnaire-40 (ALSAQ-40) score
Time frame: Baseline to 30, and 66
Change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) domain-specific subscores
Time frame: Baseline to weeks 4, 8, 12, 18, 24, 30, 42, 54, and 66
Difference in monthly change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score (delta FS)
Time frame: Onset to baseline and Baseline to weeks 30
Exploratory target-engagement objectives: Change in TDP-43 species in PBMCs
Time frame: Baseline to weeks 30, and 66
Exploratory target-engagement objectives: Change in platelet TDP-43 levels
Time frame: Baseline to weeks 30, and 66
Exploratory target-engagement objectives: Change in TDP-43-regulated splicing events
Time frame: Baseline to weeks 30, and 66
Exploratory target-engagement objectives: Change in peripheral biomarker levels
Time frame: Baseline to weeks 30, and 66
Exploratory target-engagement objectives: Change in cerebrospinal fluid biomarker levels
Time frame: Baseline to weeks 30
Exploratory target-engagement objectives: Change in TDP-43 aggregates in skin biopsies and microvesicles
Time frame: Baseline to weeks 30
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2026.
- Background: PubMed 31152038Mandrioli 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.
- Background: PubMed 39291166Gianferrari 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.
- Individual participant dataSharing planned: Yes. de-identified individual participant data will be made available after study completion upon specific request
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Amyotrophic Lateral Sclerosis
Recruiting
INdependence Through Endovascular Neuroprosthetic Technology (INTENT): an Early Feasibility Study
Neurological Disorder, ALS (Amyotrophic Lateral Sclerosis)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Giulia Gianferrari, MD principal investigator
Azienda Ospedaliero-Universitaria di Modena
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Colchicine 0.5 MG Oral Tablet in people with Amyotrophic Lateral Sclerosis, run by Azienda Ospedaliero-Universitaria di Modena at 5 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 10 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Giulia Gianferrari, MD (059-3961640, gianferrari.giulia@aou.mo.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in ALS disease progression as measured by ALS Functional rating Scale Revised (ALSFRS-R) (time frame: Baseline to Week 30 (double-blind treatment period)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07813858, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2026.