Proteomic and Inflammatory Omics Changes With Colchicine Therapy in Coronary Heart Disease

Official title

Proteomic Changes Before and After Colchicine Treatment in hsCRP-Elevated Coronary Heart Disease Patients: A Randomized Controlled Open-Label Study

Overview

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

• Drug colchicine
  Dosage form: Tablets; Dosage: 0.5mg; Frequency: Once daily; Duration: From randomization to one-year follow-up is completed

Primary outcome measures

• Differentially Expressed Proteins [Time frame: From randomization to occurence of first event, assessed up to one year]
• Enrichment analysis of inflammatory response pathways (such as NLRP3 inflammasome-related proteins, IL-1β, IL-6, and TNF-α pathways) [Time frame: From randomization to occurence of first event, assessed up to one year]

Secondary outcome measures (6)

• Genetic variants underlying the treatment-associated proteomic changes [Time frame: From randomization to occurence of first event, assessed up to one year]
• Validation of Candidate Biomarkers by ELISA [Time frame: From randomization to occurence of first event, assessed up to one year]
• Measurement of Inflammatory Biomarkers [Time frame: From randomization to occurence of first event, assessed up to one year]
• Cell-Type Deconvolution Analysis [Time frame: From randomization to occurence of first event, assessed up to one year]
• Comparison of hs-CRP Change Between Groups [Time frame: From randomization to occurence of first event, assessed up to one year]
• The incidence of the composite major adverse cardiovascular event (MACE) endpoint, defined as cardiovascular death, nonfatal myocardial infarction, ischemia-driven revascularization or stroke. [Time frame: From randomization to occurence of first event, assessed up to one year]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07462325 · 2025-GSP-GG-13

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗