---
title: Colchicine for Amyotrophic Lateral Sclerosis
nct_id: NCT03693781
overall_status: COMPLETED
phase: PHASE2
sponsor: Azienda Ospedaliero-Universitaria di Modena
study_type: INTERVENTIONAL
primary_condition: Amyotrophic Lateral Sclerosis
countries: Italy
canonical_url: "https://parkinsonspathways.com/agent/trials/NCT03693781.md"
clinicaltrials_gov: "https://clinicaltrials.gov/study/NCT03693781"
ct_last_update_post_date: 2023-03-01
last_seen_at: "2026-05-12T06:30:10.385Z"
source: ClinicalTrials.gov (mirrored, no enrichment)
---
# Colchicine for Amyotrophic Lateral Sclerosis

**Official Title:** Colchicine for Amyotrophic Lateral Sclerosis: a Phase II, Randomized, Double Blind, Placebo Controlled, Multicenter Clinical Trial

**NCT ID:** [NCT03693781](https://clinicaltrials.gov/study/NCT03693781)

## Key Facts

- **Status:** COMPLETED
- **Phase:** PHASE2
- **Study Type:** INTERVENTIONAL
- **Target Enrollment:** 54
- **Lead Sponsor:** Azienda Ospedaliero-Universitaria di Modena
- **Collaborators:** University of Modena and Reggio Emilia, University of Turin, Italy, Istituto Auxologico Italiano, IRCCS National Neurological Institute "C. Mondino" Foundation, University of Bari, IRCCS San Raffaele, University of Padova, University of Milan, Istituto Di Ricerche Farmacologiche Mario Negri, University of Campania Luigi Vanvitelli, Catholic University of the Sacred Heart
- **Conditions:** Amyotrophic Lateral Sclerosis
- **Start Date:** 2019-04-10
- **Completion Date:** 2023-01-03
- **CT.gov Last Update:** 2023-03-01

## Brief 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.

## Detailed Description

Recent evidence supports the disruption of the ubiquitin-proteasome-system and autophagy as central events in ALS. ALS is characterized by the presence of misfolded proteins prone to oligomerize into aggregates, which exert a toxic effect by affecting several intracellular functions. Heat shock protein B8 (HSPB8) recognizes and promotes the autophagy-mediated removal of misfolded mutant SOD1 and TDP-43 fragments from ALS motor neurons (MNs). Moreover, HSPB8-BAG3-HSP70 maintains the so called "granulostasis", a surveillance mechanism that avoids the conversion of dynamic stress granules (SGs) into aggregation-prone assemblies, which are a hallmark of ALS.

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.

## Eligibility

- **Minimum age:** 18 Years
- **Maximum age:** 80 Years
- **Sex:** ALL
- **Healthy Volunteers:** No

```
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).
```

## Arms

- **Colchicine 0.01mg/kg/day + 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/day
- **Colchicine 0.005 mg/kg/day + 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/day
- **Placebo + Riluzole 100 mg** (PLACEBO_COMPARATOR) — Placebo pills will be administered at fast, while taking Riluzole 100 mg/day

## Interventions

- **Colchicine 1 MG Oral Tablet** (DRUG) — Colchicine tablets depending on arm (0.01 mg/kg/day, 0.005 mg/kg/day, placebo) and on weight (\>70 kg or \<71 kg) for 30 weeks of duration.
- **Colchicine 1 MG Oral Tablet** (DRUG) — Colchicine tablets depending on arm (0.01 mg/kg/day, 0.005 mg/kg/day, placebo) and on weight (\>70 kg or \<71 kg) for 30 weeks of duration.
- **Placebo Oral Tablet** (DRUG) — Corresponding tablets for 30 weeks

## Primary Outcomes

- **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))_ — ALSFRS-R is a scale that measures disability in ALS; the scores range from 0 (maximum disability, the worst score) to 48 (no disability, the best score). We will measure total score changes from baseline to week 30 in treatment and placebo arms.

## Secondary Outcomes

- **Incidence of Treatment-Emergent Adverse Events (safety and tolerability)** _(time frame: week 30 and 54)_
- **Tracheostomy-free survival rate** _(time frame: Up to week 54)_
- **Changes in Forced Vital Capacity (FVC)** _(time frame: Up to week 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)_
- **changes in stress granules size, number and composition** _(time frame: at week 30 compared to baseline)_
- **quantification of insoluble species** _(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)_
- **effects on biomarkers of neurodegeneration** _(time frame: at week 30 compared to baseline)_
- **effects on biomarkers of inflammation** _(time frame: at week 30 compared to baseline)_

## Locations (8)

- Centro Sla, University of Bari, Bari, Italy
- Centro Sla, Istituto Auxologico Italiano, University of Milano, Milano, Milan, Italy
- Irccs Carlo Besta, Milan, Italy
- Irccs St. Raffaele Institute of Milano, Milan, Italy
- Centro Sla, Ospedale Civile S. Agostino Estense, A.O.U. Modena, Modena, Italy
- Università della Campania Gianluigi Vanvitelli, Naples, Italy
- Als Centre, "C. Mondino" National Neurological Institute, University of Pavia, Pavia, Italy
- , Neuromuscular Omnicentre Centre, Rome, Catholic University, Rome, Roma, Italy

## Recent Field Changes (last 30 days)

- `status.overallStatus` — added _(2026-05-12)_
- `status.primaryCompletionDate` — added _(2026-05-12)_
- `status.completionDate` — added _(2026-05-12)_
- `status.lastUpdatePostDate` — added _(2026-05-12)_
- `design.phases` — added _(2026-05-12)_
- `design.enrollmentCount` — added _(2026-05-12)_
- `eligibility.criteria` — added _(2026-05-12)_
- `eligibility.minAge` — added _(2026-05-12)_
- `eligibility.maxAge` — added _(2026-05-12)_
- `eligibility.sex` — added _(2026-05-12)_
- `outcomes.primary` — added _(2026-05-12)_
- `outcomes.secondary` — added _(2026-05-12)_
- `armsInterventions.arms` — added _(2026-05-12)_
- `armsInterventions.interventions` — added _(2026-05-12)_
- `sponsor.lead` — added _(2026-05-12)_
- `sponsor.collaborators` — added _(2026-05-12)_
- `results.hasResults` — added _(2026-05-12)_
- `locations.centro sla, university of bari|bari||italy` — added _(2026-05-12)_
- `locations.centro sla, istituto auxologico italiano, university of milano, milano|milan||italy` — added _(2026-05-12)_
- `locations.irccs carlo besta|milan||italy` — added _(2026-05-12)_
- `locations.irccs st. raffaele institute of milano|milan||italy` — added _(2026-05-12)_
- `locations.centro sla, ospedale civile s. agostino estense, a.o.u. modena|modena||italy` — added _(2026-05-12)_
- `locations.università della campania gianluigi vanvitelli|naples||italy` — added _(2026-05-12)_
- `locations.als centre, "c. mondino" national neurological institute, university of pavia|pavia||italy` — added _(2026-05-12)_
- `locations., neuromuscular omnicentre centre, rome, catholic university, rome|roma||italy` — added _(2026-05-12)_

---

*Canonical: https://parkinsonspathways.com/agent/trials/NCT03693781.md*  
*Source data (authoritative): https://clinicaltrials.gov/study/NCT03693781*  
*This page is a raw mirror with no AI summary, no editorial enrichment, and no Parkinson's-specific filtering.*