A Randomized, Placebo-Controlled Mechanistic Clinical Trial of Colchicine in Patients Undergoing Femoral Endarterectomy
Trial Snapshot
- Phase
- Early Phase 1
- Status
- Recruiting
- Sponsor
- University of Pennsylvania
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Molecular imaging markers of inflammation
Study Overview
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 surgery. 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. A urine pregnancy test will be done for women of childbearing age prior to starting study intervention. The study team will also obtain one 10 mL tube of research blood for future research. Participants will receive follow-up phone calls with the study team. All eligible participants will be approached for participation in an imaging visit. As part of this imaging visit, participants will 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. At the time of femoral endarterectomy, participants will repeat laboratory tests and have a sample of the femoral artery plaque stored for analysis. Participants will then have a follow-up phone call after the femoral endarterectomy to assess for any adverse events.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Other
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age >= 18 years
- •Diagnosis of peripheral artery disease
- •Stated willingness to comply with all study procedures and availability for the duration of the study
Exclusion Criteria
- •Use of colchicine or systemic anti-inflammatory medication (eg. tocilizumab) in the past 3 months
- •Allergy to colchicine
- •Presence of medication with drug-drug interaction
- •Acute limb ischemia requiring emergent intervention
- •Autoimmune/autoinflammatory disorders affecting blood vessels or with planned need for systemic anti-inflammatory medication
- •Recent (<14 days) systemic infection requiring hospitalization or ongoing treatment with antimicrobials
- •History of persistent anemia, thrombocytopenia, or neutropenia requiring hematology/oncology treatment or felt to pose unacceptable risk to colchicine by the principal investigator
- •Pregnant or lactating women
- •History of uncontrolled diabetes or an A1C >10% prior to the baseline visit
- •History of CrCl < 30 mL/minute or eGFR < 30mL/minute or end-stage renal disease ESRD on dialysis
- •History of liver disease or chronically-elevated (>3 months) ALT/AST > 3.0 x ULN
- •Claustrophobia
Arms & Interventions
Colchicine
Colchicine (0.6 mg oral daily for 4-weeks) will be the drug administered in this study.
Intervention: Colchicine (Drug)
Placebo
This arm is a matching placebo that will be administered in the same fashion as the experimental arm.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Molecular imaging markers of inflammation
Time Frame: Imaging (Week 4)
Extent of atherosclerotic plaque macrophage activity as assessed by FDG PET/CT
Secondary Outcomes
- Circulating markers of inflammation(Imaging (Week 4))
- Patient-reported walking impairment(Imaging (Week 4))