Colchicine for Amyotrophic Lateral Sclerosis

• Status: Active, not recruiting
• Trial end date: 2022-01-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Azienda Ospedaliero-Universitaria di Modena
• Collaborators: Catholic University of the Sacred Heart; IRCCS National Neurological Institute "C. Mondino" Foundation; IRCCS San Raffaele; Istituto Auxologico Italiano; Istituto Di Ricerche Farmacologiche Mario Negri; University of Bari; University of Campania "Luigi Vanvitelli"; University of Milan; University of Modena and Reggio Emilia; University of Padova; University of Turin, Italy
• Treatments: Colchicine; Riluzole

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

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).