Colchicine for Peripheral Arterial Disease
Recruiting in Palo Alto (17 mi)
Overseen byMichael Levin, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: University of Pennsylvania
Must not be taking: Colchicine, Anti-inflammatories
Disqualifiers: Diabetes, Liver disease, Autoimmune, others
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?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.
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.
What data supports the effectiveness of the drug Colchicine for Peripheral Arterial Disease?
Colchicine is known for its anti-inflammatory properties, which are beneficial in treating atherosclerotic diseases like peripheral arterial disease. Research has shown that reducing inflammation can lower the risk of cardiovascular events, and colchicine, as an anti-inflammatory agent, may help in managing peripheral arterial disease by targeting inflammation.
12345Is colchicine generally safe for humans?
Colchicine has been used in humans for various conditions, and while it is generally considered safe, it can cause side effects like gastrointestinal issues (stomach problems) and, in rare cases, blood disorders. It's important to monitor for side effects and consult with a healthcare provider during treatment.
678910How does the drug colchicine differ from other treatments for peripheral arterial disease?
Colchicine is unique because it is primarily used to reduce inflammation, which may help in conditions like peripheral arterial disease (PAD) by potentially reducing the inflammatory processes involved in atherosclerosis (buildup of fats and cholesterol in artery walls). Unlike standard treatments for PAD that focus on improving blood flow or preventing blood clots, colchicine's anti-inflammatory action offers a novel approach.
1112131415Eligibility Criteria
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.
+2 more
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.
+10 more
Trial Timeline
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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: ColchicineExperimental Treatment1 Intervention
Colchicine (0.6 mg oral daily for 4-weeks) will be the drug administered in this study.
Group II: PlaceboPlacebo Group1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of PennsylvaniaPhiladelphia, PA
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Who Is Running the Clinical Trial?
University of PennsylvaniaLead Sponsor
Doris Duke Charitable FoundationCollaborator
References
Anti-inflammatory agents in peripheral arterial disease. [2019]Inflammation is pivotally involved in coronary and peripheral atherosclerotic disease. This established concept is based on both experimental animal models of vascular inflammation and Mendelian randomization studies demonstrating a causal relationship between pro-inflammatory cytokines (e.g. interleukin-6) and cardiovascular disease risk. More recently, the reduction of cardiovascular events by use of an interleukin-1β inhibitor (canakinumab) has revived interest in the use of anti-inflammatory agents for the treatment of atherosclerotic disease, including peripheral arterial disease. In this mini review article we provide an update on the pleiotropic anti-inflammatory properties of approved drugs for use in cardiovascular disease (e.g. antiplatelets, statins, PCSK9 inhibitors) and discuss the role of targeted or untargeted anti-inflammatory atheroprotection in peripheral arterial disease by agents such as colchicine, methotrexate, anti-TNF-α agents and monoclonal antibodies against interleukin-signaling.
Omega-3 polyunsaturated fatty acid in peripheral arterial disease: effect on lipid pattern, disease severity, inflammation profile, and endothelial function. [2015]Peripheral arterial disease (PAD) is strongly associated with endothelial dysfunction and inflammation, which portend a high cardiovascular risk. Accordingly, we investigated the effects of omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation on endothelial function and inflammatory status in affected individuals.
International Consortium of Vascular Registries Consensus Recommendations for Peripheral Revascularisation Registry Data Collection. [2021]To achieve consensus on the minimum core data set for evaluation of peripheral arterial revascularisation outcomes and enable collaboration among international registries.
COMPASS for Vascular Surgeons: Practical Considerations. [2020]To suggest a practical approach for the application of data from the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial in patients with peripheral artery disease (PAD).
Protective vascular treatment of patients with peripheral arterial disease: guideline adherence according to year, age and gender. [2021]To evaluate vasoprotective pharmacological treatment of patients with peripheral arterial disease (PAD) according to: 1) year, 2) age and 3) gender.
[D-penicillamine--side effects, pathogenesis and decreasing the risks]. [2013]D-penicillamine (DPA) leads to side effects in different ways: collagen and elastin crosslinking are inhibited, which results in thin and vulnerable skin, cutis laxa, elastosis perforans serpiginosa, wound healing defects and embryopathy. Toxic influences effect thrombo- and leukocytopenia (incidence 5-15%), gastrointestinal disturbances (10-30%), changes or loss of taste (5-30%), loss of hair (1-2%), and partly proteinuria (5-20%). Acute hypersensitive reactions include DPA-allergy (2-10%). Severe adverse effects are autoimmune phenomena such as pemphigus, DPA-induced lupus erythematosus, polymyositis/dermatomyositis, membranous glomerulopathy and hypersensitivity pneumonitis (like Good-pasture's syndrome) and myasthenia (all less than 1%). In addition there are a number of rare side effects, often single observations. Risk factors include a genetic disposition (especially HLA-B8 and -DR3), poor sulphoxidizers and, to a certain degree, higher age. During pregnancy and in clinically relevant disturbances of bone marrow, liver and renal function DPA is contraindicated. The total incidence of side effects amounts to 30-60%, the withdrawal rate is 20-30%; therefore clear indications and a regular survey of DPA therapy are necessary.
D-Penicillamine--induced pemphigus syndrome. [2019]D-Penicillamine is a chelating agent which is effective in the treatment of Wilson's disease, cystinuria, and lead poisoning. In recent years, it has also been used to treat patients with rheumatoid arthritis with good results. The adverse effects of D-penicillamine are many. These include loss of taste, nephrotic syndrome, lupus erythematosus--like syndrome, polymyositis, dermatomyositis, myasthenia gravis, and agranulocytosis. Beginning in 1969, D-penicillamine was reported to induce a pemphigus eruption. We present a patient with D-penicillamine--induced pemphigus erythematosus and review previously reported cases.
Gemcitabine induced digital ischaemia and necrosis. [2022]A 70-year-old woman presented with a 7-day history of severe pain, paresthesia, oedema, acrocyanosis and punctate haemorrhagic lesions on her fingertips. The complaints began 2 days after the second cycle of a first-line chemotherapy consisting of cisplatin or carboplatin, and gemcitabine due to advanced urothelial carcinoma. At the fingertips of both hands, haemorrhagic and partly ulcerative lesions were found; these were attributed to vascular toxicity of gemcitabine. Therapeutically sympathicolysis by bilateral blockade of the brachial plexus was performed, accompanied by intravenous administration of the prostacyclin analog iloprost, fractionated heparin subcutaneously and oral therapy with corticosteroids and aspirin. Digital amputation could be avoided. Acral ischemia is a rare but probably underreported adverse effect of gemcitabine therapy and a potential source of misdiagnosis.
Cutaneous alternariosis in a patient with idiopathic pulmonary fibrosis. [2019]A 78-year-old farmer presented with symptomless skin lesions for evaluation. Two years prior, he had developed idiopathic pulmonary fibrosis (IPF) and had been treated thereafter with oral prednisolone 20 mg/day and occasionally with colchicine 1 mg/day. On examination, erythematoviolaceous, slightly infiltrated plaques, measuring approximately 5 x 9 cm, rubbery in consistency, intermingled with pustules, sometimes eroded, with distinctive borders, were noted on the dorsum of both hands and on the extensor surface of both forearms. The lesions had developed over a 20-day period. The skin of these areas was atrophic or eroded with multiple ecchymoses (Fig. 1). The abnormal laboratory findings included an elevated white blood cell count of 17,100/mm3, with 79% neutrophils, 16% lymphocytes, and 5% monocytes, C-reactive protein of 33.15 mg/dL (normal,
Vascular toxicity associated with antineoplastic agents. [2017]Vascular complications associated with antineoplastic agents are being reported with increasing frequency. Such vascular toxicity is clinically heterogeneous, ranging from asymptomatic arterial lesions to a fatal thrombotic microangiopathic syndrome. Mitomycin is most commonly implicated in the thrombotic microangiopathic syndrome, while bleomycin, either alone or in combination with a vinca alkaloid or cisplatin, appears to be an important cause of Raynaud's phenomenon. Acute arterial ischemic events, ie, myocardial infarction and cerebrovascular accidents, occur most frequently after cisplatin-based combination chemotherapy. Putative mechanisms for such toxicity include drug-induced endovascular damage, perturbation of the clotting system, platelet activation, an abnormality of thromboxane-prostacyclin homeostasis, autonomic dysfunction, vasculitis, and stimulation of fibroblasts. More than one mechanism may be operative in an individual patient. Better documentation of the incidence and types of vascular toxicity and studies to help elucidate the pathogenesis and management of such toxicity are needed.
Drug treatment of peripheral arterial disease in the elderly. [2018]Peripheral arterial disease (PAD) may be asymptomatic, may be associated with intermittent claudication or may be associated with critical limb ischaemia. Coronary artery disease (CAD) and other atherosclerotic vascular disorders may coexist with PAD. Persons with PAD are at increased risk for all-cause mortality, cardiovascular mortality and mortality from CAD. Smoking should be stopped and hypertension, diabetes mellitus, dyslipidaemia and hypothyroidism treated. HMG-CoA reductase inhibitors (statins) reduce the incidence of intermittent claudication and improve exercise duration until the onset of intermittent claudication in persons with PAD and hypercholesterolaemia. Antiplatelet drugs such as aspirin or clopidogrel (especially the latter), ACE inhibitors and statins should be given to all persons with PAD. beta-Adrenoceptor antagonists should be given if CAD is present. The phosphodiesterase type 3 inhibitor cilostazol improves exercise time until intermittent claudication. Chelation therapy should be avoided. Correct implementation of medical therapy significantly reduces the excess mortality associated with PAD. In addition, medical therapy may result in significant improvements in walking ability that may obviate the need for lower extremity angioplasty with stenting and bypass surgery.
[Drug therapy in peripheral arterial occlusive disease]. [2006]Drugs used for improvement or stabilization of peripheral circulation include antiaggregants or anticoagulants for secondary prevention of arteriosclerosis, vasoactive substances and fibrinolytic agents. -Two prospective trials document that aspirin or the combination of aspirin and dipyridamole reduce progression of arterial occlusive disease significantly in comparison to placebo. Aspirin is best suited for secondary prevention of recurrent stenoses or occlusions after carotid or femoral endarterectomy, whereas anticoagulants are preferred in patients with embolism and after peripheral implantation of venous bypasses. -Significant improvement of walking distance is achieved by several compounds influencing blood rheology. The effect does not exceed that obtained by physical training. If reconstructive arterial surgery or percutaneous transluminal angioplasty are not possible, some patients with rest pain or gangrene may be successfully treated by intraarterial administration of prostaglandin E1.
[The clinico-instrumental evaluation of the efficacy of picotamide in treating chronic obstructive arteriopathies of the lower extremities]. [2012]In 25 patients (19 males and 6 females) suffering from chronic arteriopathy of lower extremities at Fontaine stage II, the clinical efficacy of picotamide was investigated in double blind, cross over placebo-controlled study. Patients were assigned randomly to the treatment with placebo or picotamide (900 mg/die) for three months and, after 15 days of wash-out, to the treatment with picotamide or placebo for the same period. Painfree walking distance and ankle/arm systolic pressure ratio improved significantly only during picotamide treatment. Laboratory monitoring revealed a significant decrease in platelet aggregation and an increase of fibrinogen degradation products only during picotamide treatment. Three patients during picotamide treatment referred transient gastrointestinal discomfort (nausea, vomiting and diarrhoea); however in no case the treatment was suspended because of the appearance of these symptoms. These results indicate that picotamide is an effective drug in the management of chronic arteriopathy of lower extremities.
Prevalence of peripheral arterial disease - results of the Heinz Nixdorf recall study. [2021]This report presents population-based estimates of the prevalence of peripheral arterial disease (PAD), chronic critical limb ischemia (CLI), and Moenckeberg's medial calcinosis (MC) in Germany.
Calcified plaque modification alters local drug delivery in the treatment of peripheral atherosclerosis. [2018]Calcific atherosclerosis is a major challenge to intraluminal drug delivery in peripheral artery disease (PAD).