Sonodynamic Therapy in the Treatment of Perivascular Adipose Tissue on Patients With PAD and Claudication

The purpose of this trial is to evaluate the safety and efficacy of sonodynamic therapy (SDT) in reducing the inflammation of perivascular adipose tissue and increasing peak walking time (PWT) among peripheral artery disease (PAD) patients with symptom of intermittent claudication.

Study Overview

• Status: Withdrawn
• Conditions: Peripheral Arterial Disease
• Intervention / Treatment: Combination product: Sonodynamic therapy(SDT)

Detailed Description

Atherosclerotic lower extremity PAD affects the living quality of more than 20 million people in the world. PAD is associated with a major decline in functional status and claudication is the most evident symptom. Current claudication therapies reveal significant limitations. Pharmacotherapy and exercise are recommended in 2016 AHA/ACC Guideline on the management of lower extremity PAD patients with claudication. However, they may not achieve an ideal clinical therapeutic effect. Furthermore, endovascular procedure may not be feasible, durable or cost-effective, especially in femoropopliteal arteries.

The aim of this trial is to verify the hypothesis that SDT can reduce the inflammation of PVAT and improve PWT among PAD patients with symptom of intermittent claudication.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 40-80 years
• Patients with atherosclerotic peripheral artery disease with symptoms of moderate to severe intermittent claudication (defined as ability to walk at least 2, but not more than 11 minutes on a graded treadmill test using the Gardner protocol)
• Femoral popliteal artery with 50% stenosis by ultrasound
• Stable use of low to moderate dose statin and the permitted statin drugs/ doses: atorvastatin 20 mg, simvastatin 40 mg, rosuvastatin 10 mg, pravastatin, 40 mg, fluvastatin 80 mg or lovastatin 40 mg for at least 6 weeks prior to screening
• Written informed consent

Exclusion Criteria:

• Severe aorto-iliac arteries stenosis or occlusion documented by noninvasive and invasive anatomic assessments
• Critical limb ischemia or other comorbid conditions that limit walking ability
• Non-atherosclerotic peripheral artery stenosis
• Active systemic inflammatory disease or have an infectious disease within 1 month prior to enrollment
• Systemic disorders such as hepatic, renal, hematologic, and malignant disease
• Allergic to contrast media with iodine
• Contraindication to CTA
• Allergic to DVDMS
• Diagnosis of porphyria
• Pregnant women and nursing mothers
• Patient who is attending other clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Sonodynamic therapy(SDT); Sonodynamic therapy(SDT) treatment is the combination of sonosensitizer administration and target atherosclerotic lesions ultrasound exposure.

Combination product: Sonodynamic therapy(SDT); Sonodynamic Therapy (SDT) Sinoporphyrin Sodium (DVDMS) as sonosensitizer, is dissolved in 0.9% sodium solution for following skin test and intravenous injection. 0.01mg/ml DVDMS solution (0.1ml) is prepared for skin test followed by 0.04 mg/ml DVDMS solution intravenous injection(0.2mg/kg).The target atherosclerotic lesions are marked on the corresponding skin with ultrasound guidance and underwent ultrasound exposure after 4 hours incubation. The therapeutic ultrasonic transducer is fixed to the marked skin site for 15 min of each lesion. Ultrasound parameters included intensity of 2.1W/cm2 for each lesion, resonance frequency: 1.0 MHz and duty factor: 30%.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in PVAT Density, as assessed by CTA	The changes in CT attenuation (HU) of perivascular adipose tissue(PVAT) as assessed by CTA.	Measured at Baseline, 1, 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in peak flow velocity, as assessed by doppler ultrasound	The changes of the systolic and diastolic peak flow velocity of the affected segments by doppler ultrasound.	Measured at Baseline, 1, 3 months
Incidence of adverse events	Allergic to sunshine,hepatic or renal dysfunction,thyroid dysfunction	Measured at Baseline, 1, 3 months
PWT change, mins	Changes from baseline peak walking time (PWT) at 1 month is assessed by graded treadmill test (Gardner protocol). The patient continues the test until walking can no longer be tolerated because of claudication symptoms.	Measured at Baseline, 1, 3 months
Plasma adipokines level	Including adiponectin, vaspin, apelin, leptin, visfatin, resistin and FABP	Measured at Baseline, 1, 3 months
Plasma inflammation cytokine level	Including Interleukin-6(IL-6), IL-10, IL-1β, TGF-α, CRP, EGF, glutathione(GSH) and TGSH.	Measured at Baseline, 1, 3 months

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Harbin Medical University
• Investigators: Principal Investigator: Ye Tian, MD,PHD, First Affiliated Hospital of Harbin Medical University

Study record dates

Study Major Dates

• Study Start (Anticipated): June 20, 2019
• Primary Completion (Anticipated): May 30, 2020
• Study Completion (Anticipated): May 30, 2020

Study Registration Dates

• First Submitted: May 27, 2019
• First Submitted That Met QC Criteria: May 27, 2019
• First Posted (Actual): May 30, 2019

Study Record Updates

• Last Update Posted (Actual): April 15, 2021
• Last Update Submitted That Met QC Criteria: April 13, 2021
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Peripheral Arterial Disease; Peripheral Vascular Diseases
• Other Study ID Numbers: Ye Tian PVAT

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No