Reducing Inflammation to Improve Vascular and Bone Outcomes With Low-dose Colchicine in CKD

Официальное название

Reducing Inflammation to Improve Vascular and Bone Outcomes With Low-dose Colchicine in CKD: A Pilot Randomized Open-Label Trial (RESOLVE-CKD Trial)

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Low-dose Colchicine at 0.5mg daily
  Intervention group will receive LoDoCo (Colchicine 0.5mg), oral, once daily.
• Другое Usual Care
  Participants will receive usual care according to standard clinical practice and treating physician discretion.

Первичные конечные точки

• Change in Coronary Artery Calcification Agatston Scores [Срок оценки: Baseline, 12 months]

Вторичные конечные точки (12)

• Change in Coronary Artery Calcification Volume Scores [Срок оценки: Baseline, 12 months]
• Change in Cardiac Artery Calcification Mass Scores [Срок оценки: Baseline, 12 months]
• Change in Serum Klotho Levels [Срок оценки: Baseline, 6 months, 12 months]
• Change in Fetuin A Levels [Срок оценки: Baseline, 6 months, 12 months]
• Change in Serum Phosphate levels [Срок оценки: Baseline, 6 months, 12 months]
• Change in Serum Calcium Levels [Срок оценки: Baseline, 6 months, 12 months]
• Change in Parathyroid Hormone (PTH) levels [Срок оценки: Baseline, 6 months, 12 months]
• Change in C-terminal Fibroblast Growth Factor 23 (FGF23) Levels [Срок оценки: Baseline, 6 months, 12 months]
• Change in Fibroblast Growth Factor 23 (FGF23) Levels [Срок оценки: Baseline, 6 months, 12 months]
• Change in Bone-Specific Alkaline Phosphatase (BSAP) Levels [Срок оценки: Baseline, 6 months, 12 months]
• Change in C-terminal Telopeptide of Type I Collagen (CTX) [Срок оценки: Baseline, 6 months, 12 months]
• Change in Tartrate-Resistant Acid Phosphatase 5b (TRAP-5b) Levels [Срок оценки: Baseline, 6 months, 12 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of Texas Southwestern Medical Center — Dallas

Публикации

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• Kiraz S, Ertenli I, Arici M, Calguneri M, Haznedaroglu I, Celik I, Pay S, Kirazli S. Effects of colchicine on inflammatory cytokines and selectins in familial Mediterranean fever. Clin Exp Rheumatol. 1998 Nov-Dec;16(6):721-4. PMID 9844766
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Идентификаторы

NCT: NCT07654231 · STU20260896 · 99077

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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