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CompletedNCT03457662SMART-PADUpdated Aug 21, 2024

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

A Phase 1/2 interventional study of OMC and pseudo-SDT and OMC and SDT in Peripheral Arterial Disease, Atherosclerosis and Cardiovascular Diseases, sponsored by First Affiliated Hospital of Harbin Medical University. Completed at 1 site in China. Open to participants aged 40 Years and older. Per ClinicalTrials.gov, last updated 2024-08-21.

Sponsored by First Affiliated Hospital of Harbin Medical University · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
32
Allocation
Randomized
Ages
40 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Peripheral Arterial Disease
  • Atherosclerosis
  • Cardiovascular Diseases
03

Who can participate

Ages eligible
40 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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)
    1. Aged ≥40 years
    1. Resting ABI \< 0.9 or ABI decreases > 0.15 after treadmill test regardless of the ABI at rest
    1. 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
    1. 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
    1. Written informed consent

Exclusion criteria

Exclusion Criteria:

    1. Critical limb ischemia or other comorbid conditions that limit walking ability (claudication must be the consistent primary exercise limitation)
    1. Inability to complete treadmill testing per protocol requirements
    1. Two treadmill tests are completed at baseline to confirm reproducibility of results; those who deviates >25% are excluded
    1. Severe aorto-iliac arteries stenosis or occlusion documented by noninvasive and invasive anatomic assessments
    1. Active systemic inflammatory disease or have an infectious disease within 1 month prior to enrollment
    1. Allergic to DVDMS
    1. Diagnosis of porphyria
    1. Pregnant women and nursing mothers
    1. Contraindications of PET/CT
    1. Concurrent enrollment in another clinical trial
    1. Presence of any clinical condition that in the opinion of the principal investigator makes the patient not suitable to participate in the trial
04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
32 participants (actual)

Study arms

  • Active comparator
    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.

    Combination Product: OMC and pseudo-SDT

  • Experimental
    OMC and SDT

    OMC and SDT are administrated in this arm.

    Combination Product: OMC and SDT

Interventions

  • Combination productOMC 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.

  • Combination productOMC 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.

05

What researchers measure

Primary outcomes

  1. Change in MDS TBR

    The primary efficacy endpoint is the change of target-to-background ratio (TBR) within the most diseased segment (MDS) of index-leg artery at 30-day follow-up after treatment, defined as ratio of the standardized uptake value (SUV) in artery wall to background venous activity within the MDS of index- leg artery assessed by PET/CT.

    Time frame: Measured at baseline, 1month.

Secondary outcomes

  1. AS TBR change, (%)

    Change from baseline to 30-day in active slice (AS) assessed by PET/CT. The mean max AS TBR is defined as average mean maximal TBR of only slices with TBR \>1.6 from index-leg at baseline.

    Time frame: Measured at baseline, 1month.

  2. WV TBR change, (%)

    Change from baseline to 30-day in whole vessel (WV) TBR assessed by PET/CT. The mean max WV TBR is defined as a single whole vessel average mean maximal TBR of all the slices that compose the index vessel.

    Time frame: Measured at baseline, 1month.

  3. PWT change, s

    Change 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.

    Time frame: Measured at baseline, 1month.

  4. COT change, s

    Change from baseline claudication onset time (COT) at 1 month is assessed by graded treadmill test (Gardner protocol). The patient continues the test until calf muscle discomfort is first noticed.

    Time frame: Measured at baseline, 1month.

  5. Pre-exercise ABI

    Ankle-Brachial Index (ABI) is the ratio of the blood pressure at the ankle to the blood pressure of the upper arm. Pre- exercise ABI is collected routinely with the patient supine immediately prior to a treadmill test.

    Time frame: Measured at baseline, 1month.

  6. Diameter stenosis, (%)

    Estimation of the maximum diameter stenosis of the affected segments by doppler ultrasound.

    Time frame: Measured at baseline, 1month.

  7. WIQ score

    The Walking Impairment Questionnaire (WIQ) assesses the severity of the subjective walking impairment on distance, speed, and stair climbing scales. It is administered as a self report. Range: Minimum score is 0.2, maximum 100.

    Time frame: Measured at baseline, 1month.

  8. SF-36 score

    The patient reported SF-36 data assesses subjective physical limitations, leg symptoms, social function, treatment satisfaction, and quality of life. It is administered as a self report. Higher scores are indicative of better outcome. The summary scores is compiled by taking the mean of five subscales generated from the original questions. Range: Minimum score is 11.1, maximum 85.

    Time frame: Measured at baseline, 1month.

Other outcomes

  1. The number and percentage of mildly/severely calcified sites

    According to the Hounsfield unit calcium density of PET/CT, the arterial sites were divided into 3 groups: non-calcified sites (\< 130 HU), mildly calcified sites (130-399 HU) and severely calcified sites (≥400 HU). The exploratory endpoints is the number and percentage of mildly/severely calcified sites.

    Time frame: Measured at baseline, 1month.

  2. The CT values of mildly and severely calcified sites

    The exploratory endpoints is the CT values of mildly and severely calcified sites.

    Time frame: Measured at baseline, 1month.

  3. The TBR values of mildly and severely calcified sites

    The exploratory endpoints is the TBR values of mildly and severely calcified sites.

    Time frame: Measured at baseline, 1month.

06

Study locations

1 site
  • The First Affiliated Hospital of Harbin Medical University
    Harbin, Heilongjiang 150000, China
07

References and documents

Publications

  • 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. PubMed 32966832 ↗
08

Registry details

Key details

Study ID
NCT03457662
Lead sponsor
First Affiliated Hospital of Harbin Medical University
Responsible party
Ye Tian (Professor, MD, PhD, First Affiliated Hospital of Harbin Medical University) — Principal investigator
First posted
Mar 7, 2018
Start date
Mar 15, 2018
Primary completion
Dec 18, 2018
Completion
Apr 11, 2019
Last update
Aug 21, 2024

Study contacts

YE TIAN, MD, PhD
study chair · First Affiliated Hospital of Harbin Medical University

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
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