COlchicine iN Circulating Inflammatory Markers After StrokE (CONCISE)

Sponsor

University College Dublin (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06062277

Collaborator

Mater Misericordiae University Hospital (Other)

Enrollment

Location

Arm

Anticipated Duration (Months)

4.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this phase 2, before-and-after interventional study is to investigate the effect of colchicine treatment on serum biomarkers of inflammation in patients with a history of stroke and atherosclerosis.

Participants meeting inclusion criteria will have blood samples drawn at baseline, will be dispensed colchicine 0.5mg daily for a treatment period of 30 days and have blood samples drawn again at follow-up. All blood samples will be analysed for a panel of inflammatory blood markers and the change in blood inflammatory markers from baseline to end of treatment will be calculated.

Condition or Disease	Intervention/Treatment	Phase
Ischemic Stroke Atherosclerosis	Drug: Colchicine 0.5 MG	Phase 2

Detailed Description

Patients with a history of stroke or TIA, atherosclerosis and hsCRP≥2mg/L at baseline will be eligible for inclusion. Participants ≥18 years and ≤90 years, with no race, ethnicity or sex exclusions will be recruited. The target sample size is 91 participants. The sample size was calculated based on a paired two-sided t-test, using a 33% effect size, setting alpha at 0.05 and power at 0.8, and allowing for up to 20% non-adherence with colchicine.

Participants will receive 30 days treatment with pleiotropic anti-inflammatory agent colchicine 0.5mg tablets orally once daily for 30 days. A panel of blood inflammatory markers will be drawn pre and post treatment. Outcomes will be the calculated change in blood inflammatory marker panel, including hsCRP and IL-6, comparing before treatment levels with after treatment levels. This is a before and after paired cohort study, each participant will act as their own control.

All participants will receive the intervention study medication, colchicine 0.5mg orally once daily. Medication adherence will be ascertained by pill count and tolerability assessed using the MAQ questionnaire. MAQ questionnaire is a 6 item questionnaire which will assess each participants perception of the convenience, taste, look and smell, effect, side-effects and overall acceptability of the study drug, colchicine, on a likert scale.

Baseline characteristics will be collected including participant demographics, past medical history, medication use, blood pressure, BMI. These assessments will be repeated at the follow-up visit. This information will be collected with participant consent via participant reported history, physical exam, office blood pressure and weight measurement, and with reference to medical notes.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

91 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Before and after intervention paired cohort studyBefore and after intervention paired cohort study

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Colchicine in Circulating Inflammatory Markers After Stroke

Anticipated Study Start Date :

Oct 1, 2023

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Jun 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Other: Single Arm Study Paired cohort before and after study. Each participant will act as their own control. All participants will receive the intervention: study drug colchicine 0.5mg orally once daily for a treatment period of 30 days.	Drug: Colchicine 0.5 MG one oral tablet daily for 30 days

Arm

Intervention/Treatment

Other: Single Arm Study

Paired cohort before and after study. Each participant will act as their own control. All participants will receive the intervention: study drug colchicine 0.5mg orally once daily for a treatment period of 30 days.

Drug: Colchicine 0.5 MG

one oral tablet daily for 30 days

Outcome Measures

Primary Outcome Measures

Change in hsCRP level [4 weeks]
Percentage change in hsCRP level

Secondary Outcome Measures

Change in IL-6 level [4 weeks]
Percentage change in IL-6 level
Change in TNF-alpha level [4 weeks]
Percentage change in TNF-alpha level
Change in MCP-1 level [4 weeks]
Percentage change in MCP-1 level

Other Outcome Measures

Medication tolerability, adherence and acceptability [4 weeks]
Assessed using MAQ questionnaire and pill count. The MAQ is a 6 item questionnaire which assesses the participants perception of convenience, taste, look and smell, effect, side effects, overall acceptability of the study drug on a likert scale.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Free of chronic kidney disease and eGFR>50ml/min on baseline blood tests
Serum hsCRP≥2mg/L measured during the screening phase or on routine bloods in the year prior to recruitment.
History of ischaemic stroke or TIA
presence of atheroma, including intracranial or extracranial atheroma causing ≥30% stenosis or occlusion ipsilateral to the infarct; any atheroma proximal to the infarct in patients with cryptogenic stroke or ESUS in whom an alternative mechanism is not felt to be more likely in the opinion of the physician; history of ischaemic heart disease, peripheral arterial disease or has undergone revascularisation procedures for either.

Exclusion Criteria:

Stroke or TIA likely caused by identified atrial fibrillation (permanent or paroxysmal)
Stroke or TIA caused by other identified cardiac source (intracardiac thrombus, endocarditis, metallic heart value, low ejection fraction <30%)
History of myalgia with raised CK on statin therapy
Blood dyscrasia (Hb <10g/dl; Plt <150x10^{9/L; WCC <4x10}9/L) or other history of blood dyscrasia requiring follow-up with Haematology
Impaired hepatic function (transaminases >twice ULN)
Concurrent treatment with contra-indicated drugs: CYP3A4 inhibitors (e.g. clarithromycin, erythomycin, telithromycin, macrolides, ketoconazole, itraconazole, voriconazole, tolbutamide, ritonavir, atazanavir, indinavir, other HIV protease inhibitors, verapamil, diltiazem, quinidine, digoxin, disulfiram) or P-GP inhibitors (e.g. cyclosporine) at screening
Symptomatic peripheral neuropathy or progressive neuromuscular disease
Pre-existing inflammatory bowel disease, Crohn's disease, Ulcerative colitis or chronic diarrhoea
Pre-existing inflammatory condition, intercurrent infection or other indication for regular anti-inflammatory therapies, e.g. steroid, NSAIDs, immunosuppressants.
Requirement for colchicine therapy for acute gout or gout prevention or other rheumatological disorder.
Known sensitivity of allergy to colchicine.
Active malignancy or known Hepatitis B, C or HIV infection.
Dementia or cognitive impairment sufficient to impair independence in basic activities of daily living.
People of childbearing potential (Must be >24 months free of menstrual periods)
Patient concurrently enrolled in the CONVINCE trial.