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

Official title

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

Overview

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.

Detailed description

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.

Interventions

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

Primary outcome measures

• Change in Coronary Artery Calcification Agatston Scores [Time frame: Baseline, 12 months]

Secondary outcome measures (12)

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

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

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

United States · 1 center

• University of Texas Southwestern Medical Center — Dallas

Publications

• Budoff MJ, Bhandari M, Iskander B, Ghanem AK, Kinninger A, Stark J, Garikapati V, Chilukuri S, Hankil V, Krishnan S, Punnanithinont N, Ichikawa K, Kambalapalli S, Hamal S, Lakshmanan S. Effect of colchicine on progression of known coronary atherosclerosis in patients with stable coronary artery disease: EKSTROM randomized placebo controlled trial. Eur Heart J Cardiovasc Imaging. 2026 Mar 27;27(4): PMID 41670023
• Nidorf SM, Fiolet ATL, Mosterd A, Eikelboom JW, Schut A, Opstal TSJ, The SHK, Xu XF, Ireland MA, Lenderink T, Latchem D, Hoogslag P, Jerzewski A, Nierop P, Whelan A, Hendriks R, Swart H, Schaap J, Kuijper AFM, van Hessen MWJ, Saklani P, Tan I, Thompson AG, Morton A, Judkins C, Bax WA, Dirksen M, Alings M, Hankey GJ, Budgeon CA, Tijssen JGP, Cornel JH, Thompson PL; LoDoCo2 Trial Investigators. Colc PMID 32865380
• Absalon-Aguilar A, Rull-Gabayet M, Perez-Fragoso A, Mejia-Dominguez NR, Nunez-Alvarez C, Kershenobich-Stalnikowitz D, Sifuentes-Osornio J, Ponce-de-Leon A, Gonzalez-Lara F, Martin-Nares E, Montesinos-Ramirez S, Ramirez-Alemon M, Ramirez-Rangel P, Marquez MF, Plata-Corona JC, Juarez-Vega G, Gomez-Martin D, Torres-Ruiz J. Colchicine Is Safe Though Ineffective in the Treatment of Severe COVID-19: a R PMID 34755269
• Pan Y, Fan F, Jiang J, Zhang Y. Clinical outcomes of anti-inflammatory therapies inhibiting the NLRP3/IL-1beta/IL-6/CRP pathway in coronary artery disease patients: a systemic review and meta-analysis of 37,056 individuals from 32 randomized trials. Inflamm Res. 2025 Jun 30;74(1):99. doi: 10.1007/s00011-025-02058-9. PMID 40583093
• Yang S, Huang H, Jiang K, Peng Y, Liang Z, Gong X, Li L, Li Y, Zhang B, Chen Y, Yang X. Colchicine inhibits vascular calcification by suppressing inflammasome activation through the enhancement of the Sirt2-PP2Ac signaling pathway. J Biol Chem. 2025 Jul;301(7):110381. doi: 10.1016/j.jbc.2025.110381. Epub 2025 Jun 14. PMID 40523615
• Pan Z, Cheng J, Yang W, Chen L, Wang J. Effect of colchicine on inflammatory markers in patients with coronary artery disease: A meta-analysis of clinical trials. Eur J Pharmacol. 2022 Jul 15;927:175068. doi: 10.1016/j.ejphar.2022.175068. Epub 2022 May 27. PMID 35644423
• 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
• Shi M, Zhang X, Li L, Wang Y, Zhao Q, Zhen Y, Huang Y, Liu C. Colchicine reduces inflammatory cytokines and improves symptoms in HFpEF: an observational pilot study. Front Med (Lausanne). 2026 Jan 16;12:1702293. doi: 10.3389/fmed.2025.1702293. eCollection 2025. PMID 41625765

Identifiers

NCT: NCT07654231 · STU20260896 · 99077

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗