Sonodynamic Therapy on Patients With Femoropopliteal PAD and Claudication

NCT ID: NCT03318484

Last Updated: 2021-08-23

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-30
• Study Completion Date: 2019-11-30

Brief Summary

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

Detailed Description

Atherosclerotic lower extremity PAD affects more than 20 million people in the world. PAD is associated with a major decline in functional status and claudication is the most frequent symptom. Current claudication therapies are associated with significant limitations. Pharmacotherapy cilostazol and supervised exercise are recommended in 2016 AHA/ACC Guideline on the management of lower extremity PAD patients with claudication, but cilostazol may not achieve an ideal response rate, and supervised exercise efficacy may be limited by co-morbidities and medicare reimburse. Furthermore endovascular procedure may not be feasible, durable or cost-effective, especially in femoropopliteal arteries.

The aim of this trial is to test the hypothesis that SDT improves PWT by inhibiting atherosclerotic plaques inflammation in femoropopliteal arteries PAD patients compared to optimal medical care (OMC) within 6 month. An estimated 80 eligible patients will be randomly divided into tow groups: OMC and SDT combined with OMC. Recruitment will be performed over 6 months and patients will be followed for 6 months; the anticipated total study duration will be 2 years.

Finally, this trial investigate the safety and efficacy of SDT in PAD patients with intermittent claudication and explore new end-points to evaluate therapeutic effects using PET-CT imaging as well as traditional endpoints.

Conditions

Peripheral Arterial Disease; Atherosclerosis; Cardiovascular Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Optimal Medical Care

Optimal medical care (OMC) only is administrated in this arm. OMC is established according to the standards established by the 2016 ACC-AHA Guidelines for the Management of Patients with Peripheral Artery Disease in order to promote best practices for risk factor management.

Group Type: ACTIVE_COMPARATOR

Optimal Medical Care

Intervention Type: DRUG

Aspirin 100mg once a day, Atorvastatin 20mg once a day and Antihypertensive Agents if necessary.

Optimal Medical Care and SDT

OMC and sonodynamic therapy (SDT) are administrated in this arm.

Group Type: EXPERIMENTAL

Optimal Medical Care

Intervention Type: DRUG

Aspirin 100mg once a day, Atorvastatin 20mg once a day and Antihypertensive Agents if necessary.

Sonodynamic therapy

Intervention Type: COMBINATION_PRODUCT

SDT treatment is the combination of sonosensitizer administration and target atherosclerotic lesions ultrasound exposure. 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 15min of each lesion. Ultrasound parameters included intensity of 1.8W/cm2 for femoral lesions, resonance frequency: 1.0 MHz and duty factor: 30%.

Interventions

Optimal Medical Care

Aspirin 100mg once a day, Atorvastatin 20mg once a day and Antihypertensive Agents if necessary.

Intervention Type: DRUG

Sonodynamic therapy

SDT treatment is the combination of sonosensitizer administration and target atherosclerotic lesions ultrasound exposure. 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 15min of each lesion. Ultrasound parameters included intensity of 1.8W/cm2 for femoral lesions, resonance frequency: 1.0 MHz and duty factor: 30%.

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

Inclusion Criteria

1. 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)

2. Aged ≥40 years

3. Resting ABI < 0.9 or ABI decreases > 0.15 after treadmill test regardless of the ABI at rest

4. Presence of significant stenosis but not occlusion of femoropopliteal arteries including the common femoral artery, superficial femoral artery and popliteal artery as determined by: Duplex ultrasound imaging OR lower extremity computed Tomography Angiography (CTA) OR lower extremity magnetic resonance angiography (MRA) OR lower extremity catheter-based contrast arteriography. Each of these noninvasive and invasive anatomic assessments will identify patients with at least a 50% stenosis in the affected segment

5. 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

6. Written informed consent

Exclusion Criteria

1. Critical limb ischemia or other comorbid conditions that limit walking ability (claudication must be the consistent primary exercise limitation)

2. Inability to complete treadmill testing per protocol requirements

3. Two treadmill tests are completed at baseline to confirm reproducibility of results; those who deviates >25% are excluded

4. Severe aorto-iliac arteries stenosis or occlusion documented by noninvasive and invasive anatomic assessments

5. Allergic to DVDMS

6. Diagnosis of porphyria

7. Pregnant women and nursing mothers

8. Contraindications of PET/CT

9. Concurrent enrollment in another clinical trial

10. Presence of any clinical condition that in the opinion of the principal Investigator or the sponsor makes the patient not suitable to participate in the trial

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Harbin Medical University

OTHER

Sponsor Role: collaborator

First Affiliated Hospital of Harbin Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

YE TIAN, MD, PhD

Role: STUDY_CHAIR

First Affiliated Hospital of Harbin Medical University

Other Identifiers

Ye Tian

Identifier Type: -

Identifier Source: org_study_id