A Mechanistic Clinical Trial of Colchicine in Patients Undergoing Femoral Endarterectomy

A Randomized, Placebo-Controlled Mechanistic Clinical Trial of Colchicine in Patients Undergoing Femoral Endarterectomy

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Peripheral Artery Disease
• Intervention / Treatment: Drug: Placebo; Drug: Colchicine

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 Type: Interventional
• Enrollment (Estimated): 24
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Kevin Dougherty, MPH; Phone Number: 215-662-2243; Email: kevin.dougherty@pennmedicine.upenn.edu
• Study Contact Backup: Name: Thomas Carabuena; Phone Number: 215-662-4830; Email: thomas.carabuena@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
      • Principal Investigator: Michael Levin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Symptomatic PAD
2. Require endarterectomy
3. Age > 18 years
4. 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. Vascular connective tissue disorders
6. Autoimmune/autoinflammatory disorders
7. Systemic infection
8. Blood dyscrasia
9. Pregnant or lactating women
10. Uncontrolled diabetes (A1C >10%)
11. History of CrCl < 30 mL/minute or ESRD (HD)
12. History of liver disease or chronically-elevated (>3 months) ALT/AST > 3.0 x ULN
13. Claustrophobia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Colchicine; Colchicine (0.6 mg oral daily for 4-weeks) will be the drug administered in this study.	Drug: Colchicine; See arm description.
Placebo Comparator: Placebo; This arm is a matching placebo that will be administered in the same fashion as the experimental arm.	Drug: Placebo; See arm description.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NLRP-3 inflammasome transcripts in femoral artery plaque specimens	Expression of NLRP-3 inflammasome transcripts will be measured using RNA sequencing	Femoral endarterectomy (Week 4)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma IL6 and hsCRP levels	Expression of plasma IL6 and hsCRP levels will be measured using RNA sequencing	Femoral endarterectomy (Week 4)
Atherosclerotic plaque macrophage activity	Atherosclerotic plaque macrophage activity will be assessed by 18F-FDG PET/CT	Femoral endarterectomy (Week 4)

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: Doris Duke Charitable Foundation
• Investigators: Principal Investigator: Michael Levin, MD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: January 8, 2024
• First Submitted That Met QC Criteria: January 8, 2024
• First Posted (Actual): January 18, 2024

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: atherosclerosis; inflammation; peripheral artery disease; colchicine; atherosclerotic cardiovascular disease
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Vascular Diseases; Peripheral Arterial Disease; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: 854429

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes