Exploratory Study of the Efficacy of Standard of Care Revascularization of the Lower Extremity

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of the standard of care revascularization of the lower extremity with the addition of revascularization of the lateral plantar artery and anterior pedal loop of the foot as treatment for diabetic peripheral neuropathy.

Detailed Description
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This is a 26 week, single arm, single-site, Investigator-initiated, exploratory trial evaluating the efficacy of the standard of care revascularization of the lower extremity with the addition of revascularization of the lateral plantar artery and anterior pedal loop of the foot as treatment for participants with PAD, diabetic neuropathy and have a clinical diagnosis of type 1 or type 2 diabetes whose main symptoms are numbness and/or tingling of the feet with or without pain. Participants who satisfy eligibility criteria may undergo standard of care revascularization of one lower extremity as required, with the addition of revascularization of the lateral plantar artery and anterior pedal loop followed by a 26-week follow-up phase. Standard of Care revascularization will be performed in any limb with ≥ 50% stenosis as determined by intra-vascular ultrasound (IVUS) at the time of planned study intervention. Participants will be evaluated prior to intervention and at 2, 4, 14 and 26 weeks after the pedal loop intervention.

Official Title
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Revascularization of the Lateral Plantar Artery and Anterior Pedal Loop of the Foot as Treatment for Diabetic Peripheral Neuropathy.

Conditions
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Diabetic Peripheral Neuropathy

Intervention / Treatment
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* Procedure: Revascularization


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female age 30 to 80 years (inclusive at first screening visit) Clinical diagnosis of type 1 or type 2 diabetes as diagnosed by HbA1c ≥ 6.5% or current treatment Clinical signs and symptoms of diabetic peripheral neuropathy bilaterally affecting the lower extremities, in the investigator's opinion, which may include neuropathic symptoms (e.g., numbness, tingling, burning sensation, sharp pains, sensitivity to touch) and decreased distal sensation (e.g., decreased vibration, pinprick or pain sensation, monofilament) HbA1c ≤ 11% (historical results allowed if performed within the past 90 days) Females of child-bearing potential who are willing to use contraceptive measures to prevent pregnancy for the duration of the study Willing to attend all scheduled study visits and undergo all study procedures Clinical diagnosis of Peripheral Artery Disease (PAD) Be able to understand, speak, read and write English Have medical insurance or financial means to cover the cost of the revascularization procedure and follow-up visits with the Interventional Radiologist Exclusion Criteria: Inability to undergo angiogram with revascularization Unilateral neuropathic findings or symptoms Vitamin B-12 level < 400 pg/ml (historical results allowed if performed within the past 30 days) * Known causes of peripheral neuropathy other than diabetes, e.g., Amyloidosis, Tangier disease, Fabry's disease, hereditary sensory autonomic neuropathy, alcohol-related neuropathy, drug-induced neuropathy (e.g., chemotherapy, antibiotics, anti-retroviral agents, other neurotoxic agents) hypothyroidism that is not well controlled, rheumatoid arthritis or autoimmune disorders requiring treatment with corticosteroids, anti-tumor necrosis factor or immune-modulating medicines Known history of Hepatitis B, C, or HIV Lower limb amputation, including toe Lower extremity inoperable occlusive vascular disease Inability to provide informed consent History of bleeding disorders History of diabetic ulcers to the lower extremities History of any surgical bypass of the lower extremities prior to randomization History of previous revascularization of the lower extremities prior to randomization End Stage Renal Disease (ESRD) requiring or on dialysis Thyroid Stimulating Hormone -TSH >10.0 uu/mL* Potassium > 5.5 mmol/L. * Calcium < 8.5 mg/dL or > 11mg/dL * Hemoglobin < 9.0 g/dL * Female that is pregnant, breastfeeding or intends to become pregnant during the study period Clinically significant abnormal ECG findings, in the opinion of the Investigator Participation in another clinical trial with investigational drug or device at time of screening Any other clinically significant disorders or prior therapy that, in the opinion of the Investigator, would make the participant unsuitable for the study or unable to comply with the protocol requirements

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: 26 week, single arm, single site
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Single Arm<br>This is a 26 week, single arm, single-site, Investigator-initiated, exploratory trial evaluating the efficacy of the standard of care revascularization of the lower extremity with the addition of revascularization of the lateral plantar artery and anterior pedal loop of the foot as treatment for participants with PAD, diabetic neuropathy and have a clinical diagnosis of type 1 or type 2 diabetes whose main symptoms are numbness and/or tingling of the feet with or without pain. | Procedure: Revascularization<br>* Angiogram and IVUS with revascularization of the lateral plantar artery and pedal arch on target foot.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intra-epidermal Nerve Fiber Density | Change from baseline in intra-epidermal nerve fiber density (IENFD) via skin biopsy of the revascularized foot over the extensor digitorum brevis muscle (EDBM) at week 26. | 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intra-epidermal Nerve Fiber Density | Number and percent of participants whose IENFD have increased by at least 20% from baseline | 14 and 26 weeks | 
| Utah Early Neuropathy Scale | Number and percentage of participants with improvement on Utah Neuropathy Scale (UENS) | 14 and 26 weeks | 
| Sural Nerve Action Potential Amplitude | Number and percentage of participants with improvement of sural nerve action potential amplitude | 14 and 26 weeks | 
| Sudoscan | Number and percentage of participants with 20% improvement on Sudoscan | 14 and 26 weeks | 
| Intra-epidermal Nerve Fiber Density | Number and percentage of participants with improvement of intra-epidermal nerve fiber density | 14 weeks | 
| Neuropathic Pain Syndrome Inventory | Improvement in quality of life as measured by the Neuropathic Pain Syndrome Inventory | 14 and 26 weeks | 
| Patency of Lateral Plantar Artery | Number and percentage of participants with patency of lateral plantar artery per ultrasound | 14 and 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Type 1 Diabetes, Type 2 Diabetes, Neuropathy, Diabetic Peripheral Neuropathy, Peripheral Artery Disease, PAD