Definite or probable amyotrophic lateral sclerosis MedDRA version: 20.0 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders MedDRA version: 20.0 Level: LLT Classification code 10052889 Term: ALS System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: COLCHICINA LIRCA - 1 MG COMPRESSE 60 COMPRESSE
Product Name: Colchicina
Product Code: Colchicina
Pharmaceutical Form: Tablet
INN or Proposed INN: COLCHICINA
CAS Number: 64-86-8
Current Spo
Sponsors
AZIENDA OSPEDALIERO-UNIVERSITARIA POLICLINICO DI MODENA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients diagnosed with a laboratory supported , clinically “probable” or “definite” amyotrophic lateral sclerosis according to the Revised El Escorial criteria (Brooks, 2000) - Sporadic ALS - ALS phenotypes: classic or bulbar - Female or male patients aged between 18 and 80 years old - Disease duration from symptoms onset no longer than 18 months at the screening visit - Patients treated with a stable dose of Riluzole (100 mg/day) for at least 30 days prior to screening - Patients with a weight > 50 kg and a BMI =18 - Patients with a FVC (Forced Vital Capacity) equal or more than 65 % predicted normal value for gender, height, and age at the screening visit - Patients able and willing to comply with study procedures as per protocol - Patients able to understand, and capable of providing informed consent at screening visit prior to any protocol-specific procedures - Use of highly effective contraception both for males and females Are the trial subjects under 18? no Number of subjects for this age range: 1 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 29 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: - Prior use of colchicine - Prior allergy/sensitivity to colchicine - Receiving colchicine or other anti-inflammatory drugs (such as corticosteroids, methotrexate, anti-neoplastic, Interleukin 1-1b antagonist, Tumor necrosis factor-alpha inhibitor) - Receiving food or co-medications such as strong-moderate cytochrome P450 3A4 inhibitors that will result in elevated plasma level of colchicine - Inflammatory disorders (SLE, Rheumatoid arthritis, connective tissue disorder) or chronic infections (HIV, hepatitis B or C infection) or significant history of malignancy - Severe renal (eGFR 2x Upper limit of normal) - Existing blood dyscrasia (e.g., myelodysplasia) - White blood cells<4,000/mm³, platelets count<100,000/mm³, hematocrit<30% - Severe comorbidities (heart, renal, liver failure), autoimmune diseases or any type of interstitial lung disease - Patients who underwent non invasive ventilation, tracheotomy and /or gastrostomy - Women who are pregnant or breastfeeding - Participation in pharmacological studies within the last 30 days before screening - Patients with known pathogenic mutations (SOD1, TARDBP, FUS, C9ORF72) - Patients with familial ALS defined as presence of at least one first degree family member (parents/son/daughter/brother/sister) affected by ALS - Patients with the following ALS phenotypes: flail arm, flail leg, UMN-p, respiratory, PLS, progressive muscular atrophy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to assess whether different colchicine doses decrease disease progression, measured through ALSFRS-R (ALS Functional Rating Scale-Revised), in ALS patients compared to the control arm.;Secondary Objective: - To evaluate colchicin safety and tolerability in ALS patients; - To analyse colchicine efficacy in enhancing autophagy quantifying mRNA and protein levels of p62, LC3, TFEB, ATGs, HSPB8, BAG3, BAG1, HSP70, and HSF1, also in muscle biopsy of patients (optional); - To identify changes in stress granules response and composition; - Measure of the overall levels and the relative ratio between soluble and insoluble species of TDP-43, TDP-43 fragments, SQSTM1/p62, UBQLN, OPTN in fibroblasts and lymphoblasts; - To study colchicine effects on extracellular vesicles secretion of TDP-43, hyperphosphorylated TDP-43, SQSTM1/p62, UBQLN and OPTN; - To study colchicine effects on peripheral and CSF biomarkers: creatinine, albumin, CK, and vitamin D, phosphorylated neurofilaments heavy chain, IL18 and its endogenous inhibitor IL-18BP, MCP1 and IL17; - To evaluate colchicine efficacy in terms of survival and forced vital capacity (FVC) progression ;Primary end point(s): Proportion of patients exhibiting a positive response (considered as a decrease in ALS progression) comparing baseline and treatment end (week 30) between colchicine and placebo arm, using ALS Functional Rating Scale—Revised (ALSFRS-R);Timepoint(s) of evaluation of this end point: The primary endpoint will be assessed after 30 weeks from the start of treatment with colchicine or placebo | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Absolute and relative change from baseline of the score of ALSAQ-40 (Amyotrophic Lateral Sclerosis Specific Assessment Questionnnaire) at weeks 8, 30 and 54;Timepoint(s) of evaluation of this end point: The endpoint will be evaluated at weeks 8, 30 and 54 after the start of treatment with colchicine or placebo | — |
Countries
Italy
Contacts
Public ContactCentro coordinatore
Ospedale Civile S. Agostino Estense
Outcome results
None listed