Colchicine Use in Intracranial Atherosclerotic Disease

NCT05503225 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CREC No. 2022.008
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

Intracranial atherosclerotic disease (ICAD) is a major ischaemic stroke aetiology in Asia. Influenced by genetics, lifestyle and metabolic risk factors. From the SAMMPRIS cohort, 1-year stroke recurrence risk was 13% even with intensive medical therapy. In this pilot randomized, double-blind, placebo-controlled trial, the investigators shall recruit 44 patients with recent ischaemic stroke due to intracranial atherosclerosis (ICAD) with ≥ 50% stenosis. Patients will be randomly assigned to either low-dose colchicine (0.5mg daily) (n=22) or placebo (n=22) for 12 months. High-resolution magnetic resonance vessel wall imaging will be performed at baseline and 12 months. The primary endpoint is a composite of regression of intracranial stenosis, plaque volume, or occurrence of any major adverse cardio- or cerebrovascular events at 12 months. The investigators shall also evaluate safety endpoints including diarrhea, marrow suppression, infections, neuromuscular dysfunction. No studies had focused on the use of colchicine in patients with ICAD, which is highly prevalent in Asia. Results from this pilot trial will provide an important basis for a larger-scale main trial in the future.

Conditions

ICAD - Intracranial Atherosclerotic Disease

Keywords

ICAD; CVA; colchicine

Outcome Measures

Primary Outcomes (3)

• Regression of intracranial stenosis

  Regression in stenosis of ≥ 15% using the WASID method.

  at 12 months

• Regression of plaque volume

  Regression of plaque burden of ≥ 15% compared to baseline.

  at 12 months

• Major adverse cardio- or cerebrovascular events (MACE)

  Occurrence of any major adverse cardio- or cerebrovascular events (MACE).

  at 12 months

Secondary Outcomes (6)

• Longitudinal changes in ICAD stenosis

  at 12 months

• Longitudinal changes in plaque volume

  at 1,3,6,9,12 months

• Longitudinal changes in resolution of plaque enhancement

  at 1,3,6,9,12 months

• Longitudinal changes in white matter hyperintensity volume

  at 12 months

• Longitudinal changes in number of silent lacunes

  at 12 months

Study Arms (2)

Colchicine

ACTIVE COMPARATOR

0.5 mg of Colchicine for 12 months to be orally taken

Drug: Colchicine 0.5 MG

Standard of care

NO INTERVENTION

Standard medical therapy

Interventions

Colchicine 0.5 MG DRUG

0.5mg Orally Taken Colchicine

Colchicine

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chinese patients aged 40-80 years old
• Patients with symptomatic ICAD of ≥ 50% stenosis in middle cerebral arteries, basilar artery. Degree of stenosis will be quantified by computer tomographic angiography (CTA), magnetic resonance imaging (MRI) or digital subtraction angiography (DSA) by the WASID method (13). Symptomatic ICAD is defined as ischemic stroke or transient ischemic attack with clinical or radiological signs correspond to the vascular territory supplied by the disease vessel.
• Patients with first-ever ischaemic stroke within 8 weeks of recruitment

You may not qualify if:

• Patients who are unable to provide an informed consent
• Patients who are contraindicated to contrast MRI scans, e.g. non-MRI compatible pacemaker, claustrophobia, known gadolinium-based contrast allergy, estimated glomerular filtration rate \< 30mL/min/1.73m2, etc.
• Patients who have absolute or relative contraindications to colchicine therapy, e.g. colchicine allergy, neuromuscular disorders, haematological diseases, chronic diarrhea, estimated glomerular filtration rate \< 30mL/min/1.73m2, chronic liver disease, etc.
• Patients with intracranial stenosis not due to atherosclerosis, e.g. vasculitis, vasospasm, Moyamoya disease, etc.
• Pregnancy
• Patients with elevated creatine kinase level at randomisation stage of study.
• Recurrent gouty arthritis that requires colchicine for \> 3 months per year;
• Inflammatory bowel disease or chronic diarrhea;
• Neuromuscular disease or a nontransient creatine kinase level that was greater than three times the upper limit of the normal range (unless due to infarction) for \> 3 months;
• Clinically significant nontransient hematologic abnormalities with hemoglobin \<10g/dL, white blood cell \< 4x10\^9, or platelet \< 100x10\^9/L for \> 3 months;
• Alcoholism;
• Long term systemic glucocorticoid therapy

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

Chinese University of Hong Kong

Hong Kong, Hong Kong

RECRUITING

MeSH Terms

Conditions

Intracranial Arteriosclerosis

Interventions

Colchicine

Condition Hierarchy (Ancestors)

Intracranial Arterial Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Central Study Contacts

Fung Tsang

CONTACT

+852 35051853; sftsang@cuhk.edu.hk

Trista Hung

CONTACT

tristahung@cuhk.edu.hk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: A 1:1 recruitment ratio of treatment to control group will be recruited. A sample size of 25 patients per arm will be required, therefore a total sample size of 50 will be required. Assuming a 30% rate of lost-to-follow-up, a sample size of 72 will be required.

Study Record Dates

• First Submitted: July 29, 2022
• First Posted: August 16, 2022
• Study Start: November 28, 2022
• Primary Completion: September 30, 2025
• Study Completion (Estimated): May 31, 2026
• Last Updated: September 4, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)