Study Purpose:
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.Study Status:
Not recruiting
Disease:
Amyotrophic Lateral Sclerosis
Study Type:
Interventional
Type of Intervention:
Drug
Intervention Name:
Colchicine 1 MG Oral Tablet, Placebo Oral Tablet
Placebo:
Yes
Phase:
Phase 2
Study Chair(s)/Principal Investigator(s):
Jessica Mandrioli, Azienda Ospedaliero-Universitaria di Modena
Clinicaltrials.gov ID:
Neals Affiliated?
No
Coordinating Center Contact Information
Full Study Summary:
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.
Study Sponsor:
Azienda Ospedaliero-Universitaria di Modena
Estimated Enrollment:
54
Estimated Study Start Date:
04 / 10 / 2019
Estimated Study Completion Date:
01 / 03 / 2023
Posting Last Modified Date:
03 / 01 / 2023
Date Study Added to neals.org:
10 / 03 / 2018
Minimum Age:
18 Years
Maximum Age:
80 Years
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
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< 30ml/min/1.73m2), or liver failure or liver aminotransferase (ALT/AST > 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 the following ALS phenotypes: flail arm, flail leg, UMN-p, respiratory, PLS, progressive muscular atrophy.
- 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 known pathogenic mutations (SOD1, TARDBP, FUS, C9ORF72).
Centro Sla, University of Bari
Bari
Italy
Centro Sla, Istituto Auxologico Italiano, University of Milano, Milano
Milano
Italy
Irccs Carlo Besta
Milano
Italy
Irccs St. Raffaele Institute of Milano
Milano
Italy
Centro Sla, Ospedale Civile S. Agostino Estense, A.O.U. Modena
Modena 41126
Italy
Università della Campania Gianluigi Vanvitelli
Napoli
Italy
Als Centre, "C. Mondino" National Neurological Institute, University of Pavia
Pavia
Italy
, Neuromuscular Omnicentre Centre, Rome, Catholic University, Rome
Roma
Italy