Clinical trial NCT03318484: Sonodynamic Therapy on Patients With Femoropopliteal PAD and Claudication
Official title: Sonodynamic Therapy Manipulate Atherosclerosis Regression Trial Among Patients With Femoropopliteal PAD and Claudication
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Peripheral Arterial Disease
Atherosclerosis
Cardiovascular Diseases
Lead sponsor: First Affiliated Hospital of Harbin Medical University
Sponsor class: OTHER
Collaborators: name: Harbin Medical University
First posted: 2017-10-24
Enrollment: 0
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) 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.

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

Primary outcomes:
measure: PWT change, mins
timeFrame: Measured at baseline, 1, 3 and 6 months.
measure: MDS TBR change, (%)
timeFrame: Measured at baseline, 1 and 3 months.
Secondary outcomes:
measure: COT change, mins
timeFrame: Measured at baseline, 1, 3, and 6 months.
measure: AS TBR change, (%)
timeFrame: Measured at baseline, 1 and 3 months.
measure: WV TBR change, (%)
timeFrame: Measured at baseline, 1 and 3 months.
measure: Serum inflammation cytokine level
timeFrame: Measured at baseline, 1, 3, and 6 months.
measure: Pre-exercise ABI
timeFrame: Measured at baseline, 1, 3, and 6 months.
measure: Post-exercise ABI
timeFrame: Measured at baseline, 1, 3, and 6 months.
measure: Intimal-medial thickness, (mm)
timeFrame: Measured at baseline, 1, 3, and 6 months.
measure: Peak flow velocity, (cm/s)
timeFrame: Measured at baseline, 1, 3, and 6 months.
measure: Vessels' diameter, (mm)
timeFrame: Measured at baseline, 1, 3, and 6 months.
measure: Diameter stenosis, (%)
timeFrame: Measured at baseline, 1, 3, and 6 months.
measure: WIQ score
timeFrame: Measured at baseline, 1, 3, and 6 months.
measure: SF-36 score
timeFrame: Measured at baseline, 1, 3, and 6 months
Other outcomes:
Locations:
Study officials:
affiliation: First Affiliated Hospital of Harbin Medical University
name: YE TIAN, MD, PhD
role: STUDY_CHAIR
References: