ICAD - Intracranial Atherosclerotic DiseasePhase 2NCT05503225
Colchicine Use in Intracranial Atherosclerotic Disease
A Phase 2 study testing Colchicine 0.5 MG in people with ICAD - Intracranial Atherosclerotic Disease, run by Chinese University of Hong Kong at 1 site in Hong Kong.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- ICAD - Intracranial Atherosclerotic Disease
- What is being tested?
- Colchicine 0.5 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteHong Kong
- Study dates
- 28 Nov 2022to 31 May 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Trista Hung contact
Hong Kong1 site, 1 recruiting
- Recruiting
Chinese University of Hong Kong
Hong Kong
Bonaventure Yiu Ming IP, MB ChB, 852-28902002, bonaventureip@cuhk.edu.hk
About this study
Official title: Colchicine Use in Intracranial Atherosclerotic Disease - a Pilot Open-labelled Randomized Trial
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.
Read the 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.
- Being tested
- Colchicine 0.5 MG
- Keywords
- ICAD, CVA, colchicine
- Medical subject headings
- Intracranial Arteriosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Colchicine 0.5 MGDrug
0.5mg Orally Taken Colchicine
| Study group | Role | What they receive |
|---|---|---|
| Colchicine | Active comparator | 0.5 mg of Colchicine for 12 months to be orally taken Receives: Drug: Colchicine 0.5 MG |
| Standard of care | No intervention | Standard medical therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Regression of intracranial stenosis
Regression in stenosis of ≥ 15% using the WASID method.
Measured: at 12 months
Regression of plaque volume
Regression of plaque burden of ≥ 15% compared to baseline.
Measured: at 12 months
Major adverse cardio- or cerebrovascular events (MACE)
Occurrence of any major adverse cardio- or cerebrovascular events (MACE).
Measured: at 12 months
Secondary outcomes (6)
Longitudinal changes in ICAD stenosis
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.
Measured: at 12 months
Longitudinal changes in plaque volume
Longitudinal changes in plaque volume by DSA or equivalent imaging techniques.
Measured: at 1,3,6,9,12 months
Longitudinal changes in resolution of plaque enhancement
Longitudinal changes in resolution of plaque enhancement by DSA or equivalent imaging techniques.
Measured: at 1,3,6,9,12 months
Longitudinal changes in white matter hyperintensity volume
Longitudinal changes in white matter hyperintensity volume by MRI or equivalent imaging.
Measured: at 12 months
Longitudinal changes in number of silent lacunes
Longitudinal changes in number of silent lacunes by MRI or equivalent imaging.
Measured: at 12 months
Longitudinal changes in cognitive ability
Longitudinal changes in cognitive ability by assessment: Hong Kong Montreal Cognitive Assessment (5-min Protocol).
Measured: at 1,3,6,9,12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2022
- Study start28 Nov 2022
- Primary completion30 Sep 2027 (estimated)
- Study completion31 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ICAD - Intracranial Atherosclerotic DiseaseStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. IP Yiu Ming Bonaventure, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05503225
- Sponsor's protocol ID
- CREC No. 2022.008
- Status last verified
- Jul 2026
- First submitted
- 29 Jul 2022
- Last updated
- 30 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No