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Sonodynamic Therapy Manipulates Atherosclerosis Regression Trial on Patients With Carotid Atherosclerotic Plaques

Phase 1
Withdrawn
Conditions
Carotid Atherosclerosis
Interventions
Combination Product: pseudo-SDT
Combination Product: Sonodynamic therapy (SDT)
Registration Number
NCT03382249
Lead Sponsor
First Affiliated Hospital of Harbin Medical University
Brief Summary

Sonodynamic therapy (SDT) is a new treatment for carotid atherosclerotic plaque. The aim of this study is to assess the safety and efficacy of this technique.

Detailed Description

Carotid atherosclerotic plaque is an important cause of ischemic stroke, causes about 30% stroke/TIA attacks. Patients with carotid stenosis face an escalated risk of MI, PAD, and death. Treatments for patients with carotid plaque include lifestyle changes, medical management(such as control of hyperlipidemia, hypertension, and diabetes) and carotid revascularization(carotid endarterectomy or carotid artery stenting). Studies have suggested that plaque morphology and composition are important determinants of plaque stability, using serial MR imaging of the carotid artery allowed observation of changes in plaque composition. Contrast enhanced ultrasound (CEUS) is a well accepted technique for detection of intraplaque neovascularization(IPN) in carotid atherosclerotic disease.

The aim of this trial is to assess the safety and efficacy of SDT. The SDT can induce macrophage elimination and inhibiting matrix degradation, which will promote plaque lipid depletion, inflammation level decrease and changes in other plaque tissue components, leading to plaque stabilization and reduction.

An estimated 80 eligible patients will be randomly divided into two groups: optimal medical care (OMC) combined with pseudo-SDT and OMC combined with SDT. Recruitment will be performed over 1 year and patients will be followed for 3 months; the anticipated total study duration will be 2 years.

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
Inclusion Criteria
  • Age 18- 80 years
  • Carotid artery with 30%~70% stenosis by ultrasound and plaque thickness>2.5mm
  • Patients without transient ischemic attack, minor stroke or amaurosis fugax within 6 months
  • Patients' LDL-c level below 100 mg/dL(2.6mmol/L), well-controlled blood pressure(systolic BP<140 and diastolic BP<90 under resting conditions) and diabetes(HbA1c<7%)
  • Written informed consent
Exclusion Criteria
  • Non-atherosclerotic carotid artery stenosis
  • Contraindication to MRI( uses pacemaker, has metallic implants, claustrophobia)
  • Acute MI, acute coronary syndrome or stroke within 4 weeks prior to visit or during run-in
  • Severe cerebral artery stenosis, atrial fibrillation or MRI detected thrombosis that would cause stroke
  • Previous significant adverse reaction to a statin
  • Systemic disorders such as hepatic, renal, hematologic, and malignant disease
  • Medical history that might limit the individual's ability to take trial treatments for the duration of the study
  • Allergic to DVDMS or sonovue
  • Diagnosis of porphyria
  • Pregnant women and nursing mothers
  • History of bilateral carotid endarterectomy or has immediate plans for carotid endarterectomy
  • Not willing to be randomized into the 3 months trial
  • Patient who is attending other clinical trial

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
OMC and pseudo-SDTpseudo-SDTOptimal medical care (OMC) and pseudo-SDT are administrated in this arm. OMC is established according to the standards established by the 2017 China Guidelines for the Diagnosis and Treatment of Carotid Artery Stenosis in order to promote best practices for risk factor management. Pseudo-SDT combines saline injection and obstructed ultrasound exposure on targeted lesions to simulate real SDT progression.
OMC and SDTSonodynamic therapy (SDT)OMC and sonodynamic therapy (SDT) are administrated in this arm.
Primary Outcome Measures
NameTimeMethod
Change in plaque LRNC volume, as assessed by MRIMeasured at Baseline, 1, 3 months

The changes in plaque lipid-rich necrotic core (LRNC) volume as assessed by MRI.

Secondary Outcome Measures
NameTimeMethod
Change in the status of fibrous cap, as assessed by MRIMeasured at Baseline, 1, 3 months

The status of fibrous cap can be differentiated as thin/thick/ruptured assessed by MRI.

Change in plaque burden, as assessed by MRIMeasured at Baseline, 1, 3 months

The plaque burden including wall volume(mm3), vessel wall thicknesses(VWT)(mm) and percent wall volume(PWV)(%) .

Change in calcification volume, as assessed by MRIMeasured at Baseline, 1, 3 months

The changes in calcification volume as assessed by MRI.

MACCEMeasured at Baseline, 1, 3 months

incidence of major adverse cardiovascular and cerebrovascular events(MACCE)

Incidence of adverse eventsMeasured at Baseline, 1, 3 months

Allergic to sunshine,hepatic or renal dysfunction,thyroid dysfunction

Lipid changeMeasured at Baseline, 1, 3 months

To evaluate the change in lipid and lipoprotein levels as assessed by percentage change from baseline.

Change in plaque FT volume, as assessed by MRIMeasured at Baseline, 1, 3 months

The changes in plaque fibrous tissue(FT) volume as assessed by MRI.

Change in IPH volume, as assessed by MRIMeasured at Baseline, 1, 3 months

The changes in intraplaque hemorrhage (IPH) volume as assessed by MRI.

Change in MVE, as assessed by CEUSMeasured at Baseline, 1, 3 months

The changes in normalised maximal video-intensity enhancement (MVE) are calculated to quantify the density of IPN as assessed by CEUS.

Change in peak flow velocity, as assessed by doppler ultrasoundMeasured at Baseline, 1, 3 months

The changes of the systolic and diastolic peak flow velocity of the affected segments by doppler ultrasound.

Trial Locations

Locations (1)

The First Affiliated Hospital of Harbin Medical University

🇨🇳

Harbin, Heilongjiang, China

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