Atherosclerotic Cardiovascular Disease (ASCVD), Chronic Kidney Disease Mineral and Bone Disorder, Chronic Kidney Disease (Stage 3), Diabetes, Dyslipidemia, Hypertension
Conditions
Keywords
Chronic Kidney Disease, CVD, vascular calcification, Colchicine
Brief summary
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
Intervention group will receive LoDoCo (Colchicine 0.5mg), oral, once daily.
OTHERUsual Care
Participants will receive usual care according to standard clinical practice and treating physician discretion.
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Coronary Artery Calcification Agatston Scores | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Coronary Artery Calcification Volume Scores | Baseline, 12 months | Change in Coronary Artery Calcification volume (mm3) will be measured by non-contrast cardiac computed tomography (CCT) scans following standard cardiac imaging protocols. |
| Change in Cardiac Artery Calcification Mass Scores | Baseline, 12 months | Change in Cardiac Artery Calcification Mass (mg) score will be measured by non-contrast cardiac computed tomography (CCT) scans following standard cardiac imaging protocols. |
| Change in Serum Klotho Levels | Baseline, 6 months, 12 months | Circulating klotho levels (pg/mL) will be measured using standard clinical laboratory assays. |
| Change in Fetuin A Levels | Baseline, 6 months, 12 months | Circulating fetuin A levels (ng/mL) will be measured using standard clinical laboratory assays |
| Change in Serum Phosphate levels | Baseline, 6 months, 12 months | Circulating serum phosphate levels (mg/dL) will be measured using standard clinical laboratory assays. |
| Change in Serum Calcium Levels | Baseline, 6 months, 12 months | Circulating serum calcium levels (mg/dL) will be measured using standard clinical laboratory assays. |
| Change in Parathyroid Hormone (PTH) levels | Baseline, 6 months, 12 months | Circulating PTH levels (pg/mL) will be measured using standard clinical laboratory assays. |
| Change in C-terminal Fibroblast Growth Factor 23 (FGF23) Levels | Baseline, 6 months, 12 months | Circulating C-terminal FGF23 levels (RU/mL) will be measured using standard clinical laboratory assays. |
| Change in Fibroblast Growth Factor 23 (FGF23) Levels | Baseline, 6 months, 12 months | Circulating FGF23 levels (pg/mL) will be measured using standard clinical laboratory assays. |
| Change in Bone-Specific Alkaline Phosphatase (BSAP) Levels | Baseline, 6 months, 12 months | Circulating serum BSAP levels (ug/L) will be measured using standard clinical laboratory assays. |
| Change in C-terminal Telopeptide of Type I Collagen (CTX) | Baseline, 6 months, 12 months | Circulating CTX levels (ng/mL) will be measured using standard clinical laboratory assays. |
| Change in Tartrate-Resistant Acid Phosphatase 5b (TRAP-5b) Levels | Baseline, 6 months, 12 months | Circulating TRAP-5b levels (U/L) will be measured using standard clinical laboratory assays |
| Change in Sclerostin Levels | Baseline, 6 months, 12 months | Circulating sclerostin levels (pg/mL) will be measured using standard clinical laboratory assays. |
| Change in Lumbar Spine Bone Mineral Density (BMD) | Baseline, 12 months | BMD at the lumbar spine (g/cm2) will be measured by Hologic or GE Lunar DXA system following standard manufacturer protocols. |
| Change in Hip Bone Mineral Density (BMD) | Baseline, 12 months | BMD at the hip (g/cm2) will be measured by Hologic or GE Lunar DXA system following standard manufacturer protocols. |
| Change in Radius Bone Mineral Density (BMD) | Baseline, 12 months | BMD at the radius (g/cm2) will be measured by Hologic or GE Lunar DXA system following standard man |
| Change in Interleukin-6 (IL-6) Levels | Baseline, 6 months, 12 months | Circulating IL-6 levels (pg/mL) will be measured using standard clinical laboratory assays. |
| Change in Soluble Tumor Necrosis Factor Receptor 1 (sTNFR1) Levels | Baseline, 6 months, 12 months | Circulating sTNFR1 levels (pg/mL) will be measured using standard clinical laboratory assays. |
| Change in Interleukin-17 (IL-17) Levels | Baseline, 6 months, 12 months | Circulating IL-17 levels (pg/mL) will be measured using standard clinical laboratory assays. |
| Change in Intact N-Terminal Propeptide of Type I Procollagen (P1NP) Levels | Baseline, 6 months, 12 months | Circulating P1NP levels (pg/mL) will be measured using standard clinical laboratory assays. |
Countries
United States
Contacts
CONTACTAlexandra R Hartman
CONTACTPaola Lanza, MD
PRINCIPAL_INVESTIGATORJing Chen, MD
University of Texas
Outcome results
None listed