Sonodynamic Therapy Manipulates Atherosclerosis Regression Trial on Patients With PAD and Claudication

NCT ID: NCT03457662

Last Updated: 2024-08-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-15
• Study Completion Date: 2019-04-11

Brief Summary

The purpose of this trial is to evaluate the safety and efficacy of sonodynamic therapy (SDT) on reducing atherosclerotic plaques inflammation among patients with symptomatic femoropopliteal peripheral artery disease.

Detailed Description

Atherosclerotic lower extremity PAD affects more than 202 million people in the worldwide. PAD is associated with a major decline in walking 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.

SDT is a novel anti-inflammatory regimen to atherosclerosis with non-invasive, plaque-based, macrophage-targeted characteristics. We hypothesize that reducing local arterial inflammation of affected limb will ameliorate claudication symptom in patients with PAD. The main objectives of this trial are to evaluate the efficacy and safety of SDT in patients with symptomatic femoropopliteal PAD.

Thirty-two eligible participants will be randomly assigned to SDT or sham-control groups. Results of PET/CT are the prespecified primary endpoint.

Conditions

Peripheral Arterial Disease; Atherosclerosis; Cardiovascular Diseases

Study Design

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

Study Groups

OMC and pseudo-SDT

Optimal medical care (OMC) and pseudo-SDT are 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

OMC and pseudo-SDT

Intervention Type: COMBINATION_PRODUCT

OMC is established according to the 2016 ACC-AHA Guidelines for the Management of Patients with PAD. Pseudo-SDT combines saline injection and obstructed ultrasound exposure on targeted lesions to simulate real SDT progression.

OMC and SDT

OMC and SDT are administrated in this arm.

Group Type: EXPERIMENTAL

OMC and SDT

Intervention Type: COMBINATION_PRODUCT

OMC is established according to the 2016 ACC-AHA Guidelines for the Management of Patients with PAD. 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 of each lesion.

Interventions

OMC and pseudo-SDT

OMC is established according to the 2016 ACC-AHA Guidelines for the Management of Patients with PAD. Pseudo-SDT combines saline injection and obstructed ultrasound exposure on targeted lesions to simulate real SDT progression.

Intervention Type: COMBINATION_PRODUCT

OMC and SDT

OMC is established according to the 2016 ACC-AHA Guidelines for the Management of Patients with PAD. 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 of each lesion.

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 atherosclerotic plaque in 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. Active systemic inflammatory disease or have an infectious disease within 1 month prior to enrollment
• 6. Allergic to DVDMS
• 7. Diagnosis of porphyria
• 8. Pregnant women and nursing mothers
• 9. Contraindications of PET/CT
• 10. Concurrent enrollment in another clinical trial
• 11. Presence of any clinical condition that in the opinion of the principal investigator makes the patient not suitable to participate in the trial

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

Sponsors

First Affiliated Hospital of Harbin Medical University

OTHER

Sponsor Role: lead

Responsible Party

Ye Tian

Professor, MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

YE TIAN, MD, PhD

Role: STUDY_CHAIR

First Affiliated Hospital of Harbin Medical University

Locations

The First Affiliated Hospital of Harbin Medical University

Harbin, Heilongjiang, China

Countries

China

References

Jiang Y, Fan J, Li Y, Wu G, Wang Y, Yang J, Wang M, Cao Z, Li Q, Wang H, Zhang Z, Wang Y, Li B, Sun F, Zhang H, Zhang Z, Li K, Tian Y. Rapid reduction in plaque inflammation by sonodynamic therapy inpatients with symptomatic femoropopliteal peripheral artery disease:A randomized controlled trial. Int J Cardiol. 2021 Feb 15;325:132-139. doi: 10.1016/j.ijcard.2020.09.035. Epub 2020 Sep 20.

Reference Type: DERIVED

PMID: 32966832 (View on PubMed)

Other Identifiers

Ye Tian PAD

Identifier Type: -

Identifier Source: org_study_id