Colchicine for Amyotrophic Lateral Sclerosis

• Register: ClinicalTrials.gov
• Last refreshed on: 13 March 2023
• Main ID: NCT03693781
• Date of registration: 30/09/2018
• Prospective Registration: Yes
• Primary sponsor: Azienda Ospedaliero-Universitaria di Modena
• Public title: Colchicine for Amyotrophic Lateral Sclerosis Co-ALS
• Scientific title: Colchicine for Amyotrophic Lateral Sclerosis: a Phase II, Randomized, Double Blind, Placebo Controlled, Multicenter Clinical Trial
• Date of first enrolment: April 10, 2019
• Target sample size: 54
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03693781
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

Italy

Contacts

• Name: Jessica Mandrioli
• Affiliation: Azienda Ospedaliero-Universitaria di Modena

Key inclusion & exclusion 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).



Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Amyotrophic Lateral Sclerosis

Intervention(s)

Drug: Placebo Oral Tablet

Drug: Colchicine 1 MG Oral Tablet

Primary Outcome(s)

Decrease in ALS disease progression as measured by ALS Functional rating Scale Revised (ALSFRS-R) [Time Frame: comparison between baseline and treatment end (week 30)]

Secondary Outcome(s)

Changes in Forced Vital Capacity (FVC) [Time Frame: Up to week 54]

Tracheostomy-free survival rate [Time Frame: Up to week 54]

effects on biomarkers of inflammation [Time Frame: at week 30 compared to baseline]

changes in stress granules size, number and composition [Time Frame: at week 30 compared to baseline]

Incidence of Treatment-Emergent Adverse Events (safety and tolerability) [Time Frame: week 30 and 54]

Changes in quality of life [Time Frame: at 8,18,30 and 54 week]

enhancement of autophagy [Time Frame: at week 30 and 54, compared to baseline]

effects on biomarkers of neurodegeneration [Time Frame: at week 30 compared to baseline]

modifications on extracellular vesicles secretion in blood and CSF [Time Frame: at week 30 compared to baseline]

quantification of insoluble species [Time Frame: at week 30 compared to baseline]

Secondary ID(s)

Co-ALS

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

University of Milan

University of Bari

University of Campania "Luigi Vanvitelli"

IRCCS National Neurological Institute "C. Mondino" Foundation

IRCCS San Raffaele

Istituto Auxologico Italiano

Catholic University of the Sacred Heart

University of Modena and Reggio Emilia

Istituto Di Ricerche Farmacologiche Mario Negri

University of Padova

University of Turin, Italy