Colchicine for Peripheral Arterial Disease

Overseen By Clinical Research Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Pennsylvania

Must not be taking: Colchicine, Anti-inflammatories

Disqualifiers: Diabetes, Liver disease, Autoimmune, others

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how colchicine, a medication, might reduce inflammation in people with peripheral artery disease, specifically targeting the femoral arteries (the major blood vessels in the thighs). It compares the effects of colchicine to a placebo (a harmless pill with no active drug) to determine if it can lower inflammation in these arteries. Individuals diagnosed with peripheral artery disease who can commit to the study's requirements might be suitable candidates. As an Early Phase 1 trial, this research focuses on understanding how colchicine works in people, offering participants a chance to contribute to groundbreaking medical knowledge.

Will I have to stop taking my current medications?

The trial requires that you have not used colchicine or systemic anti-inflammatory medications in the past 3 months. If you are taking any medications that interact with the trial drug, you may need to stop those as well.

Is there any evidence suggesting that colchicine is likely to be safe for humans?

Research has shown that colchicine has been used in patients with peripheral artery disease (PAD) and may help lower the risk of major heart and limb problems. In these studies, most participants tolerated colchicine well, and some experienced fewer serious heart issues.

Colchicine, a common anti-inflammatory drug, has been safely used in low doses to manage inflammation in conditions like gout. It works by stopping certain proteins from causing inflammation, which helps reduce swelling in blood vessels—important for those with artery problems.

Other studies involving people with stable atherosclerosis (hardening of the arteries) found that low doses of colchicine safely reduced the risk of major heart problems by about 31%.

Overall, using colchicine in these situations appears safe and well-tolerated. However, since this is an early study phase, the specific effects and side effects in this trial may still require further investigation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Colchicine is unique for treating peripheral arterial disease because it offers a novel approach by targeting inflammation, which is a key factor in the progression of this condition. Most current treatments, like antiplatelet drugs and statins, focus on improving blood flow or reducing cholesterol levels. However, colchicine works differently by reducing inflammation directly, potentially slowing down the disease's progression. This anti-inflammatory action is the same mechanism that makes colchicine effective in treating gout, and researchers are excited to see if it could provide similar benefits for those with peripheral arterial disease.

What evidence suggests that colchicine might be an effective treatment for peripheral arterial disease?

Research has shown that colchicine, which participants in this trial may receive, can help treat lower extremity peripheral arterial disease (LEPAD), a condition affecting blood flow to the legs. Studies have found that colchicine significantly lowers the risk of serious limb problems and heart-related issues. It also reduces the chances of a stroke and the need for major amputations in people with LEPAD. Additionally, one study showed that colchicine decreased heart-related events by 31% in those with stable atherosclerosis, a condition where arteries become clogged with fatty deposits. These findings suggest that colchicine may help reduce inflammation and improve health outcomes for people with artery problems in their legs. ^{5 6 7 8 9}

Who Is on the Research Team?

Michael Levin, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for individuals with Peripheral Arterial Disease who are undergoing femoral endarterectomy. Specific eligibility criteria details were not provided, so interested participants should inquire further to determine if they qualify.

Inclusion Criteria

I am willing and able to follow all study rules and be available for its duration.

I have pain in my legs due to poor blood flow.

I need surgery to remove plaque from my artery.

Exclusion Criteria

I have a disorder affecting my blood vessels and connective tissues.

My diabetes is not under control (A1C >10%).

My kidney function is very low or I am on dialysis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive colchicine or placebo daily for 4 weeks prior to imaging

4 weeks

Baseline visit (in-person), follow-up phone calls

Imaging

Participants undergo 18F-FDG PET/CT imaging to evaluate the effects of colchicine on atherosclerotic plaque

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Follow-up phone calls

What Are the Treatments Tested in This Trial?

Interventions

• Colchicine

Trial Overview The study aims to see if colchicine can reduce inflammation in the arteries of the leg compared to a placebo. Participants will be randomly assigned to receive either colchicine or a dummy pill without any active ingredients.

How Is the Trial Designed?

Group I: Colchicine Experimental Treatment 1 Intervention

Colchicine (0.6 mg oral daily for 4-weeks) will be the drug administered in this study.

Group II: Placebo Placebo Group 1 Intervention

This arm is a matching placebo that will be administered in the same fashion as the experimental arm.

Colchicine is already approved in United States for the following indications:

Approved in United States as Colcrys for:

• Gout
• Familial Mediterranean Fever

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Doris Duke Charitable Foundation

Collaborator

Trials

65

Recruited

264,000+

Published Research Related to This Trial

Inflammation plays a crucial role in both coronary and peripheral atherosclerotic diseases, supported by studies showing a direct link between pro-inflammatory cytokines and cardiovascular risk.

Recent advancements, such as the use of the interleukin-1β inhibitor canakinumab, highlight the potential of anti-inflammatory treatments in reducing cardiovascular events and suggest that various approved drugs may offer additional anti-inflammatory benefits in managing atherosclerotic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-inflammatory agents in peripheral arterial disease. Antonopoulos, AS., Papanikolaou, E., Vogiatzi, G., et al.[2019]

In a study of 32 patients with peripheral arterial disease (PAD), supplementation with omega-3 polyunsaturated fatty acids (n-3 PUFAs) for 3 months significantly improved endothelial function, as indicated by reduced levels of soluble thrombomodulin and enhanced flow-mediated dilation.

However, n-3 PUFA supplementation did not lead to any changes in inflammatory markers, suggesting that while it may help with endothelial function, it does not impact inflammation in PAD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omega-3 polyunsaturated fatty acid in peripheral arterial disease: effect on lipid pattern, disease severity, inflammation profile, and endothelial function. Schiano, V., Laurenzano, E., Brevetti, G., et al.[2015]

A consensus was reached among 25 international vascular experts on a minimum core data set for evaluating outcomes of peripheral arterial revascularization, which includes 79 recommended items covering patient characteristics, comorbidities, procedures, and complications.

This standardized data set aims to enhance collaboration among global registries, improve data quality, and facilitate the development of real-world evidence in vascular surgery, addressing limitations of single-country studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

International Consortium of Vascular Registries Consensus Recommendations for Peripheral Revascularisation Registry Data Collection. Behrendt, CA., Bertges, D., Eldrup, N., et al.[2021]

In a study of 5962 patients with peripheral arterial disease (PAD) aged 50 and older, the use of vasoprotective treatments like antiplatelet agents, statins, and ACE inhibitors significantly increased from 1997 to 2006, indicating improved management of PAD over time.

Despite this improvement, treatment adherence remains suboptimal, especially among older patients and women, highlighting the need for targeted strategies to enhance compliance with treatment guidelines in these high-risk groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protective vascular treatment of patients with peripheral arterial disease: guideline adherence according to year, age and gender. Pâquet, M., Pilon, D., Tétrault, JP., et al.[2021]

A 70-year-old woman experienced severe fingertip symptoms, including pain and hemorrhagic lesions, after receiving gemcitabine chemotherapy for advanced urothelial carcinoma, indicating a rare vascular toxicity associated with the drug.

The treatment involved a combination of therapies, including brachial plexus blockade and iloprost, which successfully managed the symptoms and prevented the need for digital amputation, highlighting the importance of recognizing and addressing this adverse effect promptly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine induced digital ischaemia and necrosis. Holstein, A., Bätge, R., Egberts, EH.[2022]

D-penicillamine (DPA) can cause a wide range of side effects, affecting skin integrity, blood cell counts, and leading to autoimmune disorders, with an overall incidence of side effects reported between 30-60%.

Due to the potential for serious adverse effects, including severe autoimmune reactions and contraindications in certain populations (like pregnant women), careful monitoring and clear indications for use are essential when prescribing DPA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[D-penicillamine--side effects, pathogenesis and decreasing the risks]. Grasedyck, K.[2013]

In a study of 25 patients with chronic arteriopathy, picotamide (900 mg/day) significantly improved pain-free walking distance and ankle/arm systolic pressure ratio compared to placebo, indicating its efficacy in managing this condition.

While some patients experienced mild gastrointestinal discomfort during treatment, the side effects were transient and did not lead to treatment discontinuation, suggesting that picotamide is generally safe for use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The clinico-instrumental evaluation of the efficacy of picotamide in treating chronic obstructive arteriopathies of the lower extremities]. Canonico, V., Ammaturo, V., Guarini, P., et al.[2012]

A 78-year-old farmer with idiopathic pulmonary fibrosis developed skin lesions diagnosed as alternariosis, caused by the fungus Alternaria alternata, which was confirmed through laboratory tests and biopsy.

Treatment with oral itraconazole and a reduced dose of prednisolone led to complete healing of the skin lesions within 3 months, with no recurrence observed after two years, indicating the efficacy of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cutaneous alternariosis in a patient with idiopathic pulmonary fibrosis. Ioannidou, DJ., Stefanidou, MP., Maraki, SG., et al.[2019]

Vascular complications from cancer treatments are becoming more common, with serious conditions like thrombotic microangiopathic syndrome linked to drugs like mitomycin and bleomycin causing Raynaud's phenomenon.

Cisplatin-based chemotherapy is associated with acute arterial ischemic events, such as heart attacks and strokes, highlighting the need for better understanding and management of these vascular toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vascular toxicity associated with antineoplastic agents. Doll, DC., Ringenberg, QS., Yarbro, JW.[2017]

The COMPASS trial demonstrated that combining low-dose rivaroxaban (2.5 mg twice daily) with daily aspirin significantly reduces major cardiovascular and limb events in patients with peripheral artery disease (PAD) compared to aspirin alone.

However, this combination therapy also increases the risk of major bleeding, so it is recommended only for PAD patients with a low bleeding risk who are at higher risk for ischemic or limb events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

COMPASS for Vascular Surgeons: Practical Considerations. Hussain, MA., Wheatcroft, M., Nault, P., et al.[2020]

Effective management of peripheral arterial disease (PAD) includes stopping smoking and treating conditions like hypertension and diabetes, which can significantly reduce the risk of mortality associated with PAD.

Medications such as statins and cilostazol improve exercise capacity in PAD patients, potentially reducing the need for invasive procedures like angioplasty or bypass surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug treatment of peripheral arterial disease in the elderly. Aronow, WS.[2018]

The study found that the prevalence of peripheral arterial disease (PAD) in Germany is 6.4% for men and 5.1% for women, increasing to 8.2% for men and 5.5% for women when considering medical history, indicating that many cases may go undetected if only relying on the ankle-brachial index (ABI).

Chronic critical limb ischemia (CLI) was very rare, affecting only 0.1% of the population studied, while Moenckeberg's medial calcinosis (MC) was present in 13.3% of men and 6.9% of women at an ABI cut-off of 1.3, suggesting that the criteria for diagnosing MC may need to be reevaluated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of peripheral arterial disease - results of the Heinz Nixdorf recall study. Kröger, K., Stang, A., Kondratieva, J., et al.[2021]

Orbital atherectomy significantly improves the delivery of paclitaxel in calcified peripheral arteries, as shown by a 2 log orders increase in drug absorption rate compared to untreated segments.

The treatment not only reduced plaque calcification by 45% but also allowed for deeper penetration of the drug, enhancing its effectiveness in combating calcific atherosclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calcified plaque modification alters local drug delivery in the treatment of peripheral atherosclerosis. Tzafriri, AR., Garcia-Polite, F., Zani, B., et al.[2018]

Aspirin and the combination of aspirin with dipyridamole have been shown to significantly reduce the progression of arterial occlusive disease compared to placebo, making them effective options for secondary prevention after procedures like carotid or femoral endarterectomy.

For patients unable to undergo reconstructive surgery, intraarterial administration of prostaglandin E1 can be a successful treatment for severe conditions like rest pain or gangrene, although the improvement in walking distance from medications does not surpass that achieved through physical training.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Drug therapy in peripheral arterial occlusive disease]. Bollinger, A.[2006]

D-Penicillamine is an effective chelating agent used to treat conditions like Wilson's disease, cystinuria, lead poisoning, and has shown positive results in rheumatoid arthritis treatment.

However, it has a range of potential adverse effects, including serious conditions like nephrotic syndrome and pemphigus erythematosus, highlighting the need for careful monitoring in patients using this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

D-Penicillamine--induced pemphigus syndrome. Yung, CW., Hambrick, GW.[2019]

Citations

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Efficacy of colchicine in lower extremity peripheral arterial ... Conclusion: Colchicine may be a useful adjunctive therapy for reducing the risk of major cardiovascular and limb-related complications in patients with LEPAD, ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0147956325000895

Efficacy of colchicine in lower extremity peripheral arterial ... Colchicine significantly reduces the risk of MALE, MACE, and ischemic stroke in LEPAD. •. Colchicine also reduces the need for major amputations and ...

3. mayoclinicproceedings.org mayoclinicproceedings.org/article/S0025-6196(24)00368-9/fulltext

Colchicine, a Novel Treatment of Peripheral Artery Disease Effects of Colchicine on Major Adverse Limb and Cardiovascular Events in Patients With Peripheral Artery Disease

4. jacc.org jacc.org/doi/10.1016/j.jacc.2023.05.055

Low-Dose Colchicine for Secondary Prevention of ... Low-dose colchicine (0.5 mg/d orally) has been shown to safely lower major adverse cardiovascular events by 31% among those with stable atherosclerosis and by ...

5. ahajournals.org ahajournals.org/doi/10.1161/circ.148.suppl_1.14449

Abstract 14449: Long-Term Colchicine for Cardiovascular ... Evidence from randomized trials suggests colchicine may reduce major adverse cardiovascular events (MACE) in patients with coronary artery disease.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39115507/

Colchicine & Limb/CV Events in Peripheral Artery Disease In patients diagnosed with PAD, the use of colchicine is associated with lower risks of MALE and cardiovascular death.

7. sciencedirect.com sciencedirect.com/science/article/pii/S1078588425003818

Low Dose Colchicine in Patients with Peripheral Artery ... Colchicine is inexpensive and has a broad anti-inflammatory effect, inhibiting NLRP3 inflammasome assembly, thereby inhibiting interleukin 1β pathway activation ...

8. atherosclerosis-journal.com atherosclerosis-journal.com/article/S0021-9150(24)01135-3/fulltext

Colchicine Use: CV & Limb Events in PAD We demonstrated that colchicine was associated with reduced risks of major adverse cardiovascular and limb events in peripheral artery disease.

9. academic.oup.com academic.oup.com/eurheartj/article/44/Supplement_2/ehad655.2071/7392585

Colchicine: Cardiovascular Risk Reduction in PAD In a real-world sample of high-risk patients with PAD and gout, colchicine did not appear to reduce the risk of adverse cardiovascular or limb ...