Peripheral Artery Disease
Conditions
Keywords
colchicine, atherosclerotic cardiovascular disease, peripheral artery disease, atherosclerosis, inflammation
Brief summary
The goal of this mechanistic clinical trial is to test the effects of reducing inflammatory signaling in femoral artery atherosclerotic plaques. Researchers will compare patients receiving colchicine to patients receiving placebo to determine the effect of colchicine on the inflammatory state of atherosclerotic femoral arteries.
Detailed description
Patients with peripheral artery disease who will be undergoing femoral endarterectomy will be randomized 1:1 to receive colchicine (0.6mg oral) or placebo daily for 4 weeks prior to 18F-FDG PET/CT imaging. At the baseline visit, study procedures will be reviewed with eligible participants and the study team will obtain written informed consent. Baseline blood samples for laboratory studies will be collected and assayed, as well as additional blood samples for research. Participants will completed study questionnaires at baseline and at the imaging visit. Participants will receive follow-up phone calls with the study team. All eligible participants will be approached for participation in an imaging visit. At the imaging visit, participants will repeat laboratory tests and undergo non-invasive molecular imaging to evaluate the effects of colchicine on the extent of atherosclerotic plaque macrophage activity as assessed by 18F-FDG PET/CT.
Interventions
DRUGColchicine
See arm description.
DRUGPlacebo
See arm description.
Sponsors
University of Pennsylvania
Doris Duke Charitable Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age \>= 18 years 2. Diagnosis of peripheral artery disease 3. Stated willingness to comply with all study procedures and availability for the duration of the study
Exclusion criteria
1. Use of colchicine or systemic anti-inflammatory medication (eg. tocilizumab) in the past 3 months 2. Allergy to colchicine 3. Presence of medication with drug-drug interaction 4. Acute limb ischemia requiring emergent intervention 5. Autoimmune/autoinflammatory disorders affecting blood vessels or with planned need for systemic anti-inflammatory medication 6. Recent (\<14 days) systemic infection requiring hospitalization or ongoing treatment with antimicrobials 7. History of persistent anemia, thrombocytopenia, or neutropenia requiring hematology/oncology treatment or felt to pose unacceptable risk to colchicine by the principal investigator 8. Pregnant or lactating women 9. History of uncontrolled diabetes or an A1C \>10% prior to the baseline visit 10. History of CrCl \< 30 mL/minute or eGFR \< 30mL/minute or end-stage renal disease ESRD on dialysis 11. History of liver disease or chronically-elevated (\>3 months) ALT/AST \> 3.0 x ULN 12. Claustrophobia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Molecular imaging markers of inflammation | Imaging (Week 4) | Extent of atherosclerotic plaque macrophage activity as assessed by FDG PET/CT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Circulating markers of inflammation | Imaging (Week 4) | Expression of plasma IL6 and hsCRP levels |
| Patient-reported walking impairment | Imaging (Week 4) | Walking impairment as reported by Walking Impairment Questionnaire |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMichael Levin, MD
University of Pennsylvania
Outcome results
None listed