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

NCT03457662 | Completed Phase 1

• 1 other identifier: Ye Tian PAD
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Peripheral Arterial Disease; Atherosclerosis; Cardiovascular Diseases

Outcome Measures

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.

  Measured at baseline, 1month.

Secondary Outcomes (8)

• AS TBR change, (%)

  Measured at baseline, 1month.

• WV TBR change, (%)

  Measured at baseline, 1month.

• PWT change, s

  Measured at baseline, 1month.

• COT change, s

  Measured at baseline, 1month.

• Pre-exercise ABI

  Measured at baseline, 1month.

Other Outcomes (3)

• The number and percentage of mildly/severely calcified sites

  Measured at baseline, 1month.

• The CT values of mildly and severely calcified sites

  Measured at baseline, 1month.

• The TBR values of mildly and severely calcified sites

  Measured at baseline, 1month.

Study Arms (2)

OMC and pseudo-SDT

ACTIVE COMPARATOR

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

OMC and SDT

EXPERIMENTAL

OMC and SDT are administrated in this arm.

Combination Product: OMC and SDT

Interventions

OMC and pseudo-SDT 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 pseudo-SDT

OMC and SDT 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.

OMC and SDT

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• First Affiliated Hospital of Harbin Medical University: lead

Study Sites (1)

The First Affiliated Hospital of Harbin Medical University

Harbin, Heilongjiang, 150000, China

Location

Related Publications (1)

• 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.

  PMID: 32966832 DERIVED

MeSH Terms

Conditions

Peripheral Arterial Disease; Atherosclerosis; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Peripheral Vascular Diseases

Study Officials

• YE TIAN, MD, PhD

  First Affiliated Hospital of Harbin Medical University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, MD, PhD

Study Record Dates

• First Submitted: March 1, 2018
• First Posted: March 7, 2018
• Study Start: March 15, 2018
• Primary Completion: December 18, 2018
• Study Completion: April 11, 2019
• Last Updated: August 21, 2024

Record last verified: 2024-08

Locations

CN (1)