Proteomic Changes Before and After Colchicine Treatment in hsCRP-Elevated Coronary Heart Disease Patients: A Randomized Controlled Open-Label Study
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 176
- 主要终点
- Differentially Expressed Proteins
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
This is an open-lable study. But while the study is in progress, the grouping information is masked from outcome assessors.
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Colchicine group
Drug: Colchicine Dosage form: Tablets Dosage: 0.5 mg Frequency: Once daily Duration: From enrollment to the one-month follow-up visit is completed.
干预措施: colchicine (Drug)
Control group
No Intervention
结局指标
主要结局
Differentially Expressed Proteins
时间窗: 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)
时间窗: 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.
次要结局
- Genetic variants underlying the treatment-associated proteomic changes(From randomization to occurence of first event, assessed up to one year)
- Validation of Candidate Biomarkers by ELISA(From randomization to occurence of first event, assessed up to one year)
- Measurement of Inflammatory Biomarkers(From randomization to occurence of first event, assessed up to one year)
- Cell-Type Deconvolution Analysis(From randomization to occurence of first event, assessed up to one year)
- Comparison of hs-CRP Change Between Groups(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.(From randomization to occurence of first event, assessed up to one year)
研究者
Xueyan Zhao
Chief physician, M.D., FACC, FESC, Doctoral supervisor
Chinese Academy of Medical Sciences, Fuwai Hospital