[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100655517":3},{"organization":4,"outcomesModule":7,"designInfo":62,"detailedDescription":74,"studyPopulation":61,"armGroups":75,"interventions":88,"overallOfficials":98,"centralContacts":102,"locations":107,"responsibleParty":183,"collaborators":186,"id":191,"slug":192,"hasResults":193,"nctId":194,"briefTitle":195,"officialTitle":196,"acronym":197,"eligibilityCriteria":198,"healthyVolunteers":193,"sex":199,"minAge":200,"maxAge":201,"enrollmentInfo":202,"targetDuration":61,"studyType":205,"phases":206,"briefSummary":208,"conditions":209,"keywords":211,"overallStatus":218,"whyStopped":61,"lastUpdateSubmitDate":219,"lastUpdatePostDateStruct":220,"startDateStruct":223,"completionDateStruct":225,"leadSponsor":227,"locationsCount":228},{"fullName":5,"class":6},"Azienda Ospedaliero-Universitaria di Modena","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":61},[9],{"measure":10,"description":11,"timeFrame":12},"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)",[14,18,22,26,29,33,37,41,45,48,51,54,58],{"measure":15,"description":16,"timeFrame":17},"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.","Baseline to Weeks 4, 8, 12, 18, 24, 30, 42, 54, and 66",{"measure":19,"description":20,"timeFrame":21},"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.","Baseline to Weeks 8, 18, 30, 42, 54, and 66",{"measure":23,"description":24,"timeFrame":25},"Tracheostomy-free survival rate","Overall survival from randomization to date of death or tracheostomy","From randomization to Week 66",{"measure":27,"description":28,"timeFrame":21},"Change in Forced Vital Capacity (FVC)","Changes in FVC score from baseline over time in both treatment groups.",{"measure":30,"description":31,"timeFrame":32},"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.","Baseline to 30, and 66",{"measure":34,"description":35,"timeFrame":36},"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.","Baseline to weeks 4, 8, 12, 18, 24, 30, 42, 54, and 66",{"measure":38,"description":39,"timeFrame":40},"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.","Onset to baseline and Baseline to weeks 30",{"measure":42,"description":43,"timeFrame":44},"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.","Baseline to weeks 30, and 66",{"measure":46,"description":47,"timeFrame":44},"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.",{"measure":49,"description":50,"timeFrame":44},"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.",{"measure":52,"description":53,"timeFrame":44},"Exploratory target-engagement objectives: Change in peripheral biomarker levels","Assess the effect of colchicine on peripheral biomarkers, including creatinine (mg\u002FdL), albumin (g\u002FdL), CRP (mg\u002FdL), urate (mg\u002FdL), and neurofilament light chain (NfL, pg\u002Fml), as well as inflammatory markers (MCP1, serpinA1, TREM2, GFAP, and CHI3L1, pg\u002Fml), measured in blood between baseline, week 30 and week 66.",{"measure":55,"description":56,"timeFrame":57},"Exploratory target-engagement objectives: Change in cerebrospinal fluid biomarker levels","Evaluate colchicine' effects on neurodegenerative (NfL, pg\u002FmL) and neuroinflammatory markers (MCP1, SerpinA1, TREM2, GFAP, CHI3L1 and UCHL1, pg\u002FmL) measured in CSF between baseline and week 30 (optional for patients)","Baseline to weeks 30",{"measure":59,"description":60,"timeFrame":57},"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)",null,{"allocation":63,"interventionModel":64,"interventionModelDescription":65,"primaryPurpose":66,"observationalModel":61,"timePerspective":61,"maskingInfo":67},"RANDOMIZED","PARALLEL","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.","TREATMENT",{"masking":68,"maskingDescription":69,"whoMasked":70},"TRIPLE","placebo will be unrecognizable from active treatment (both in tablets)",[71,72,73],"PARTICIPANT","CARE_PROVIDER","INVESTIGATOR","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\u002Fkg\u002Fday) can slow disease progression in patients with Amyotrophic Lateral Sclerosis (ALS), a rapidly progressive neurodegenerative disorder affecting upper and lower motor neurons.\n\nThe 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.\n\nThis 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.\n\nIn 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.\n\nThe 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.\n\nBiological 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.\n\nSafety 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.\n\nStatistical 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.",[76,82],{"label":77,"type":78,"description":79,"interventionNames":80},"Colchicine 0.005 mg\u002Fkg\u002Fday + 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\u002Fday",[81],"Drug: Colchicine 0.5 MG Oral Tablet",{"label":83,"type":84,"description":85,"interventionNames":86},"Placebo + Riluzole 100 mg","PLACEBO_COMPARATOR","Placebo pills will be administered at fast, while taking Riluzole 100 mg\u002Fday",[87],"Drug: Placebo Oral Tablet",[89,94],{"type":90,"name":91,"description":92,"armGroupLabels":93,"otherNames":61},"DRUG","Colchicine 0.5 MG Oral Tablet","Low-dose colchicine administered orally at 0.005 mg\u002Fkg\u002Fday 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; \\\u003C70 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.",[77],{"type":90,"name":95,"description":96,"armGroupLabels":97,"otherNames":61},"Placebo Oral Tablet","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.",[83],[99],{"name":100,"affiliation":5,"role":101},"Giulia Gianferrari, MD","PRINCIPAL_INVESTIGATOR",[103],{"name":100,"role":104,"phone":105,"phoneExt":61,"email":106},"CONTACT","059-3961640","gianferrari.giulia@aou.mo.it",[108,127,140,155,169],{"facility":109,"status":61,"city":110,"state":111,"zip":112,"country":113,"countryCode":114,"cosmosGeoPoint":115,"geoPoint":120,"contacts":121},"Centro Clinico Nemo","Milan","Milano","20162","Italy","IT",{"type":116,"coordinates":117},"Point",[118,119],12.59836,42.78235,{"lat":119,"lon":118},[122],{"name":123,"role":104,"phone":124,"phoneExt":125,"email":126},"Federica Cerri","02 9143371","+39","federica.cerri@centrocliniconemo.it",{"facility":128,"status":61,"city":129,"state":129,"zip":130,"country":113,"countryCode":114,"cosmosGeoPoint":131,"geoPoint":135,"contacts":136},"CENTRO SLA, Ospedale Civile di Baggiovara, AOU Modena","Modena","41126",{"type":116,"coordinates":132},[133,134],10.92539,44.64783,{"lat":134,"lon":133},[137],{"name":138,"role":104,"phone":139,"phoneExt":125,"email":106},"Giulia Gianferrarri","0593961640",{"facility":141,"status":61,"city":142,"state":143,"zip":144,"country":113,"countryCode":114,"cosmosGeoPoint":145,"geoPoint":149,"contacts":150},"CENTRO SLA, AOU Università Degli Studi Della Campania Luigi Vanvitelli","Naples","Napoli","80131",{"type":116,"coordinates":146},[147,148],14.26811,40.85216,{"lat":148,"lon":147},[151],{"name":152,"role":104,"phone":153,"phoneExt":125,"email":154},"Francesca Trojsi","081 566 5659","francesca.trojsi@unicampania.it",{"facility":156,"status":61,"city":157,"state":157,"zip":158,"country":113,"countryCode":114,"cosmosGeoPoint":159,"geoPoint":163,"contacts":164},"CENTRO SLA, AOU Maggiore Della Carità","Novara","28100",{"type":116,"coordinates":160},[161,162],8.62118,45.44694,{"lat":162,"lon":161},[165],{"name":166,"role":104,"phone":167,"phoneExt":125,"email":168},"Fabiola De Marchi","0321 3733962","ambulatorio.sla@maggioreosp.novara.it",{"facility":170,"status":61,"city":171,"state":171,"zip":172,"country":113,"countryCode":114,"cosmosGeoPoint":173,"geoPoint":177,"contacts":178},"CENTRO SLA, Fondazione Istituto Neurologico Nazionale Casimiro Mondino IRCCS","Pavia","27100",{"type":116,"coordinates":174},[175,176],9.15917,45.19205,{"lat":176,"lon":175},[179],{"name":180,"role":104,"phone":181,"phoneExt":125,"email":182},"Luca Diamanti","0382 380 225","luca.diamanti@mondino.it",{"type":101,"investigatorFullName":184,"investigatorTitle":185,"investigatorAffiliation":5,"oldNameTitle":61,"oldOrganization":61},"Giulia Gianferrari","sponsor-investigator",[187,189],{"name":188,"class":6},"University of Milan",{"name":190,"class":6},"Istituto Di Ricerche Farmacologiche Mario Negri","100655517","phase-2-colchicine-effect-on-amyotrophic-lateral-sclerosis-patients-100655517",false,"NCT07813858","Colchicine Effect on Amyotrophic Lateral Sclerosis Patients","A Randomized, Placebo-controlled, Multicenter, Clinical Trial of Colchicine in Amyotrophic Lateral Sclerosis","CO-ALSII","Inclusion Criteria:\n\n* Patient age strictly between 18 and 80 years at the time of screening.\n* Definitively established diagnosis of ALS (sporadic or familial) matching standardized clinical consensus parameters.\n* Stable background regimen of European gold-standard Riluzole therapy maintained at a fixed dose of 100 mg\u002Fday for a minimum of 1 month prior to baseline randomization.\n* BMI\\>17.5 Kg\u002Fm2\n* Sufficient respiratory capability, verified by an upright Forced Vital Capacity (FVC) \\>= 70% of predicted normal values at screening (highest value of three sequential tests).\n* 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.\n* Use of highly effective contraception both for males and females\n\nExclusion Criteria:\n\n* Concurrent participation or treatment within any other interventional or drug-based clinical trial.\n* 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).\n* Severe renal insufficiency, documented bone marrow suppression, or significant hematological abnormalities.\n* Known hypersensitivity or systemic intolerance to colchicine or any of the manufacturing excipients (lactose, sucrose, magnesium stearate, arabic gum).\n* Pregnancy, active lactation, or unwillingness of fertile male\u002Ffemale subjects to strictly comply with highly effective double-barrier contraception regimens throughout the study and for 100 days post-final dose.","ALL","18 Years","80 Years",{"count":203,"type":204},87,"ESTIMATED","INTERVENTIONAL",[207],"PHASE2","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.\n\nThe 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.\n\nResearchers will compare participants receiving colchicine at a dose of 0.005 mg\u002Fkg\u002Fday with those receiving placebo, both in addition to standard-of-care therapy with riluzole, to assess potential differences in disease progression.\n\nParticipants 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.",[210],"Amyotrophic Lateral Sclerosis",[210,212,213,214,215,216,217],"Colchicine","ALSFRS-R","TDP-43","Randomized Controlled Trial","Disease progression","survival","NOT_YET_RECRUITING","2026-09-07",{"date":221,"type":222},"2026-09-10","ACTUAL",{"date":224,"type":204},"2026-10",{"date":226,"type":204},"2028-12",{"name":5,"class":6},5]