Colchicine Use in Intracranial Atherosclerotic Disease
- Conditions
- ICAD - Intracranial Atherosclerotic Disease
- Interventions
- Registration Number
- NCT05503225
- Lead Sponsor
- Chinese University of Hong Kong
- 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.
- Detailed Description
Background:
Intracranial atherosclerotic disease (ICAD) is a major ischaemic stroke aetiology in Asia. Influenced by genetics, lifestyle and metabolic risk factors, over 40% of ischaemic strokes were related to ICAD in China. ICAD also predicted high risk of recurrence compared to other stroke aetiologies. From the SAMMPRIS cohort, 1-year stroke recurrence risk was 13% even with intensive medical therapy. While up-front endovascular intervention resulted in unacceptably high peri-procedural stroke risk of 20%-36%, minimal advances in medical therapy targeting ICAD had been made.
Literature clinical findings were supported by coronary plaque-imaging studies performed in human and animal models, which showed coronary plaque regression in patients with recent acute coronary syndrome and reduction in abdominal-aortic plaque inflammation in a rabbit-model. In parallel, under intensive medical therapy, ICAD plaque regression could be seen in 49% of patients. Nevertheless, recurrent stroke rate still exceeded 10% despite treatment targets of blood pressure ≤140/90, HbA1c ≤6.5%, and low-density lipoprotein (LDL) ≤1.8mmol/L in our previous cohort. There is a need to further reduce plaque growth, thrombogenicity and haemodynamic compromise by intensifying anti-atherosclerotic therapy. An updated meta-analysis showed that colchicine use in patients with high cardiovascular risk was associated with lower stroke incidence (12). However, no studies had focused on the use of colchicine in patients with ICAD, which is highly prevalent in Asia.
Objective:
In this pilot randomized, double-blind, placebo-controlled trial, the investigators aim to elucidate the efficacy and safety of low-dose colchicine (0.5mg daily) in patients with symptomatic intracranial atherosclerotic disease. The investigators hypothesize that low-dose colchicine in addition to intensive medical therapy, compared to intensive medical therapy alone, may result in more plaque regression in patients with symptomatic ICAD. Results from this pilot trial will provide an important basis for a larger-scale main trial in the future.
Methods:
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.
Significance:
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 72
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Colchicine Colchicine 0.5 MG 0.5 mg of Colchicine for 12 months to be orally taken
- Primary Outcome Measures
Name Time Method Regression of intracranial stenosis at 12 months Regression in stenosis of ≥ 15% using the WASID method.
Regression of plaque volume at 12 months Regression of plaque burden of ≥ 15% compared to baseline.
Major adverse cardio- or cerebrovascular events (MACE) at 12 months Occurrence of any major adverse cardio- or cerebrovascular events (MACE).
- Secondary Outcome Measures
Name Time Method Longitudinal changes in resolution of plaque enhancement at 1,3,6,9,12 months Longitudinal changes in resolution of plaque enhancement by DSA or equivalent imaging techniques.
Longitudinal changes in plaque volume at 1,3,6,9,12 months Longitudinal changes in plaque volume by DSA or equivalent imaging techniques.
Longitudinal changes in white matter hyperintensity volume at 12 months Longitudinal changes in white matter hyperintensity volume by MRI or equivalent imaging.
Longitudinal changes in number of silent lacunes at 12 months Longitudinal changes in number of silent lacunes by MRI or equivalent imaging.
Longitudinal changes in ICAD stenosis at 12 months Subjects will receive a novel high-resolution magnetic resonant vessel-wall imaging which depicts the degree of symptomatic stenosis, plaque burden, plaque enhancement, plaque remodelling and intraplaque haemorrhage.
Longitudinal changes in cognitive ability at 1,3,6,9,12 months Longitudinal changes in cognitive ability by assessment: Hong Kong Montreal Cognitive Assessment (5-min Protocol).
Trial Locations
- Locations (1)
Chinese University of Hong Kong
🇭🇰Hong Kong, Hong Kong