Reducing Inflammation to Improve Vascular and Bone Outcomes With Low-dose Colchicine in CKD: A Pilot Randomized Open-Label Trial (RESOLVE-CKD Trial)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Change in Coronary Artery Calcification Agatston Scores
研究概览
简要总结
The overall objective of this pilot randomized clinical trial is to determine whether low-dose Colchicine (LoDoCo) improves vascular disease including vascular calcification, peripheral arterial disease (PAD), and chronic kidney disease-mineral and bone disorder (CKD-MBD) biomarkers in patients with chronic kidney disease (CKD) stage 3 over a 12-month intervention period, compared with usual care.
Successful completion of this study will generate critical preliminary data to support a larger clinical trial aimed at evaluating inflammation-targeted therapies to mitigate CKD-MBD, including vascular calcification and related PAD, as well as osteoporosis, ultimately reducing cardiovascular events and mortality in patients with CKD. Additionally, this work has the potential to redefine the diagnostic framework for CKD-MBD.
详细描述
The investigators will conduct a randomized, open-label, outcome blinded mechanistic clinical trial in 60 adults with stage 3 chronic kidney disease (CKD) who have hypertension, diabetes, dyslipidemia, or established atherosclerotic cardiovascular disease (ASCVD).
The investigators will evaluate whether low-dose Colchicine (LoDoCo) improves coronary artery calcification (CAC) and mineral and bone disorders (MBD) over 12 months in patients with CKD, eGFR ≥30 to 59 mL/min/1.73 m², and urine albumin-to-creatinine ratio (uACR) ≥200 mg/g. Sixty participants with CKD stage 3 and increased risk of, or established, ASCVD will be randomized 1:1 to receive LoDoCo plus usual care or usual care alone. Primary outcomes include changes in Agaston scores assessed by cardiac computed tomography (CCT) from baseline to 12 months, second outcomes include changes in the individual biomarkers of MBD and vascular calcification (VC) from baseline and 12 months. Exploratory outcomes include changes in uACR, estimated glomerular filtration rate (eGFR), ankle-brachial index (ABI), and toe-brachial index (TBI). Safety and tolerability will also be evaluated. Participants will be followed at baseline, 6 months, and 12 months for data collection, with an in-person visit at 1 month for safety evaluation. Additional safety assessments for side effects may be conducted by phone at any time.
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)
入排标准
- 年龄范围
- 18 Years 至 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women aged 18-<70 years of all race/ethnicity groups
- •CKD stage 3 (estimated glomerular filtration rate (eGFR) >30 to 59 ml/min/1.73m2)
- •Urine albumin-to-creatinine ratio (uACR) ≥ 200 mg/g
- •Cardiac artery calcification (CAC) Agatston score ≥30
- •Hypertension, diabetes, dyslipidemia, or established atherosclerotic cardiovascular disease (ASCVD) (coronary artery disease (CAD), ischemic stroke, and peripheral artery disease), defined by self-report, ICD-10 codes, or the use of medications for these conditions.
- •Ability to provide informed consent.
排除标准
- •Current Colchicine therapy
- •Hepatic disease
- •Any clinically active diagnosed infection requiring systemic antimicrobial therapy, positive microbiologic evidence of infection, or infection-related hospitalization within 30 days prior to study enrollment.
- •Immunosuppression
- •Current use of chemotherapy drugs or active cancer
- •Pregnancy/breastfeeding
- •Hospitalized within the past 6 months
- •Allergic/intolerance to colchicine
- •Use of P-glycoprotein (p-gp) inhibitor (such as Verapamil, Quinidine, Amiodarone, Ritonavir, Lopinavir/ritonavir, Saquinavir, Nelfinavir)
- •Use of strong cytochrome P450 3A4 (CYP3A4) inhibitors (such as Ketoconazole, Itraconazole, Posaconazole, Voriconazole, Clarithromycin, Erythromycin)
- •Human immunodeficiency virus (HIV) infection
- •Gout attack ≥ 1 time per year
- •Severe anemia (hemoglobin < 8 g/dl for women and < 9 g/dl for men)
- •eGFR <30 ml/min/1.73m2
- •uACR <200 mg/g
- •White blood cell count (WBC) <3.0 x109/L
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 x Upper Limit of Normal (ULN)
- •Total bilirubin >2 x ULN
- •Glucose >300mg/dl
- •Uses nicotine products or other recreational drugs
- •Unable to read or speak English
- •Participant in other conflict clinical trial,
- •Unable to complete the study measurements
- •Unable to undergo to computed tomography (CT) or dual-energy X-ray absorptiometry (DXA) scans
- •Unsafe to participate in this study per investigator's judgement.
研究组 & 干预措施
Low-Dose Colchicine (LoDoCo)
Participants will receive low-dose Colchicine (LoDoCo) in addition to usual care.
干预措施: Low-dose Colchicine at 0.5mg daily (Drug)
Low-Dose Colchicine (LoDoCo)
Participants will receive low-dose Colchicine (LoDoCo) in addition to usual care.
干预措施: Usual Care (Other)
Usual Care
Participants will receive usual care alone.
干预措施: Usual Care (Other)
结局指标
主要结局
Change in Coronary Artery Calcification Agatston Scores
时间窗: Baseline, 12 months
Agatston scores (Agatston units) will be measured by non-contrast cardiac computed tomography (CCT) scans following standard cardiac imaging protocols. Coronary artery calcification will be quantified using the Coronary Artery Calcium (CAC) Agatston Score. Scores range from 0 Agatston units (no detectable coronary calcification), 1-99 Agatston units (mild calcification), 100-399 Agatston units (moderate calcification), and ≥400 Agatston units (severe calcification, high atherosclerotic burden). Higher scores indicate greater coronary artery calcification and are associated with worse outcomes.
次要结局
未报告次要终点
研究者
Jing Chen
Professor
University of Texas Southwestern Medical Center