Clinical trial NCT03457662: Sonodynamic Therapy Manipulates Atherosclerosis Regression Trial on Patients With PAD and Claudication
Official title: Sonodynamic Therapy Manipulates Atherosclerosis Regression Trial on Patients With PAD and Claudication
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Peripheral Arterial Disease
Atherosclerosis
Cardiovascular Diseases
Lead sponsor: First Affiliated Hospital of Harbin Medical University
Sponsor class: OTHER
First posted: 2018-03-07
Enrollment: 32
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in MDS TBR
timeFrame: Measured at baseline, 1month.
Secondary outcomes:
measure: AS TBR change, (%)
timeFrame: Measured at baseline, 1month.
measure: WV TBR change, (%)
timeFrame: Measured at baseline, 1month.
measure: PWT change, s
timeFrame: Measured at baseline, 1month.
measure: COT change, s
timeFrame: Measured at baseline, 1month.
measure: Pre-exercise ABI
timeFrame: Measured at baseline, 1month.
measure: Diameter stenosis, (%)
timeFrame: Measured at baseline, 1month.
measure: WIQ score
timeFrame: Measured at baseline, 1month.
measure: SF-36 score
timeFrame: Measured at baseline, 1month.
Other outcomes:
measure: The number and percentage of mildly/severely calcified sites
timeFrame: Measured at baseline, 1month.
measure: The CT values of mildly and severely calcified sites
timeFrame: Measured at baseline, 1month.
measure: The TBR values of mildly and severely calcified sites
timeFrame: Measured at baseline, 1month.
Locations:
city: Harbin
country: China
facility: The First Affiliated Hospital of Harbin Medical University
state: Heilongjiang
Study officials:
affiliation: First Affiliated Hospital of Harbin Medical University
name: YE TIAN, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.