Coronary Heart Disease (CHD)
Conditions
Keywords
Colchicine, Proteomics, Biomarkers, Olink, Anti-Inflammatory Therapy, Randomized Controlled Trial (RCT), High-Throughput Screening, Precision Medicine
Brief summary
The goal of this exploratory clinical trial is to investigate the proteomic changes induced by low-dose colchicine anti-inflammatory therapy in coronary heart disease (CHD) patients, with the aim of identifying novel biomarkers and therapeutic targets. The main questions it aims to answer are: * Whether short-term colchicine treatment induces significant changes in the plasma proteomic profile of post-PCI CHD patients with residual inflammation. * Which specific proteins or pathways are dynamically modulated by colchicine, indicating potential mechanisms of action and drug targets. * How the proteomic expression profiles differ between patients treated with colchicine and matched controls after one month. Participants, recruited based on a prior RCT framework, will be post-PCI CHD patients with elevated inflammation (hs-CRP ≥ 2 mg/L). A total of 176 participants will be enrolled: 88 in the trial group (colchicine 0.5 mg/day) and 88 in the matched control group (no intervention). All participants will complete a one-month follow-up. Peripheral blood samples will be collected at baseline and at the one-month visit for high-throughput proteomic analysis using Olink technology.
Interventions
DRUGcolchicine
Dosage form: Tablets; Dosage: 0.5mg; Frequency: Once daily; Duration: From randomization to one-year follow-up is completed
Sponsors
Chinese Academy of Medical Sciences, Fuwai Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
This is an open-lable study. But while the study is in progress, the grouping information is masked from outcome assessors.
Intervention model description
Open-label, Two-arm, Randomized, Superiority Trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis \& Treatment: Have symptoms or objective evidence of myocardial ischemia and have undergone successful Percutaneous Coronary Intervention (PCI). Inflammation Status: Have a plasma high-sensitivity C-reactive protein (hs-CRP) level ≥ 2 mg/L at the time of screening. Background Therapy: Be on guideline-directed standard medical therapy for coronary heart disease, tailored to their individual clinical condition. Informed Consent: The participant or their legally authorized representative must be capable of understanding the study and must provide written informed consent.
Exclusion criteria
* Recent Cardiac Event: Acute Myocardial Infarction within the past 1 month. Drug Intolerance: Known allergy or intolerance to colchicine. Hematologic Abnormalities: Platelet count \< 110 × 10⁹/L White blood cell count \< 4.0 × 10⁹/L Hemoglobin level \< 115 g/L Renal Impairment: Estimated Glomerular Filtration Rate (eGFR) \< 30 mL/min/1.73 m² (calculated using the MDRD formula), OR Serum creatinine level \> 2 times the upper limit of normal (ULN). Hepatic Impairment: Severe liver cirrhosis, biliary cirrhosis, or cholestasis, OR Liver enzyme (transaminase) levels \> 3 times the ULN. Bone Marrow Disorder: Known history of bone marrow hypoplasia. Severe Cardiac Conditions: New York Heart Association (NYHA) Class III-IV heart failure, OR Left Ventricular Ejection Fraction (LVEF) \< 35%, OR Moderate or severe valvular heart disease requiring intervention. Recent Cerebrovascular Event/Instability: Stroke within the past 3 months, or current cardiogenic shock or hemodynamic instability. Active Malignancy: Concurrent active tumor or cancer. Chronic Pulmonary Disease: Chronic Obstructive Pulmonary Disease (COPD) or other chronic lung diseases. Inflammatory Bowel Disease (IBD) or Chronic Diarrhea: e.g., Crohn's disease, ulcerative colitis. Uncontrolled Comorbidities: Any other uncontrolled disease or condition that, in the investigator's judgment, would place the participant at undue risk by participating in the study. Active Systemic Inflammation/Infection: Presence of systemic inflammation or acute infection at the time of enrollment. Concurrent Steroid Use: Current use or planned initiation of systemic corticosteroid therapy during the study period (excluding topical or inhaled steroids). Pregnancy/Breastfeeding: Women who are pregnant, planning to become pregnant, or breastfeeding. Concurrent Trial Participation: Participation in another interventional clinical trial within the past 3 months that may interfere with the outcomes of this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Differentially Expressed Proteins | From randomization to occurence of first event, assessed up to one year | Using high-throughput mass spectrometry techniques (such as Olink, SOMAscan , LC-MS/MS or NULISA), the identification and quantification of differentially expressed proteins in the blood (plasma/serum) samples of patients in the colchicine treatment group and the placebo control group were compared at baseline and after treatment. |
| Enrichment analysis of inflammatory response pathways (such as NLRP3 inflammasome-related proteins, IL-1β, IL-6, and TNF-α pathways) | From randomization to occurence of first event, assessed up to one year | Using high-throughput mass spectrometry techniques (such as Olink, SOMAscan , LC-MS/MS, ELISA or MSD), the identification and quantification of differentially expressed proteins in the blood (plasma/serum) samples of patients in the colchicine treatment group and the placebo control group were compared at baseline and after treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Genetic variants underlying the treatment-associated proteomic changes | From randomization to occurence of first event, assessed up to one year | To identify genetic variants underlying the treatment-associated proteomic changes |
| Validation of Candidate Biomarkers by ELISA | From randomization to occurence of first event, assessed up to one year | Top differentially expressed proteins from the primary proteomic screen will be confirmed using quantitative enzyme-linked immunosorbent assays in the entire cohort. |
| Measurement of Inflammatory Biomarkers | From randomization to occurence of first event, assessed up to one year | Serum levels of high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) were quantified using commercial enzyme-linked immunosorbent assay kits according to the manufacturers' instructions. |
| Cell-Type Deconvolution Analysis | From randomization to occurence of first event, assessed up to one year | To infer the predominant cellular origins contributing to the observed plasma proteomic changes, the investigators will perform deconvolution analysis using established reference datasets (e.g., from single-cell RNA sequencing studies of blood cells and vasculature). This will estimate the relative contributions of cell types such as neutrophils, platelets, monocytes, and endothelial cells to the protein signature. |
| Comparison of hs-CRP Change Between Groups | From randomization to occurence of first event, assessed up to one year | The absolute and relative (%) change in high-sensitivity C-reactive protein levels from baseline to the end of the treatment period will be compared between the colchicine and placebo groups. |
| The incidence of the composite major adverse cardiovascular event (MACE) endpoint, defined as cardiovascular death, nonfatal myocardial infarction, ischemia-driven revascularization or stroke. | From randomization to occurence of first event, assessed up to one year | — |
Outcome results
None listed