Sonodynamic Therapy Manipulates Atherosclerosis Regression Trial on Patients With Carotid Atherosclerotic Plaques (SMART-C)

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.

Study Overview

• Status: Withdrawn
• Conditions: Carotid Atherosclerosis
• Intervention / Treatment: Combination product: pseudo-SDT; Combination product: Sonodynamic therapy (SDT)

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.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo 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 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.	Combination product: pseudo-SDT; Pseudo-SDT combines saline injection and obstructed ultrasound exposure on targeted lesions to simulate real SDT progression.
Experimental: OMC and SDT; OMC and sonodynamic therapy (SDT) are administrated in this arm.	Combination product: Sonodynamic therapy (SDT); Sonodynamic therapy(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 for 15min of each lesion. Ultrasound parameters included intensity of 1.6W/cm2 for carotid lesions, resonance frequency: 1.0 MHz and duty factor: 30%.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in plaque LRNC volume, as assessed by MRI	The changes in plaque lipid-rich necrotic core (LRNC) volume as assessed by MRI.	Measured at Baseline, 1, 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in plaque FT volume, as assessed by MRI	The changes in plaque fibrous tissue(FT) volume as assessed by MRI.	Measured at Baseline, 1, 3 months
Change in IPH volume, as assessed by MRI	The changes in intraplaque hemorrhage (IPH) volume as assessed by MRI.	Measured at Baseline, 1, 3 months
Change in calcification volume, as assessed by MRI	The changes in calcification volume as assessed by MRI.	Measured at Baseline, 1, 3 months
Change in the status of fibrous cap, as assessed by MRI	The status of fibrous cap can be differentiated as thin/thick/ruptured assessed by MRI.	Measured at Baseline, 1, 3 months
Change in plaque burden, as assessed by MRI	The plaque burden including wall volume(mm3), vessel wall thicknesses(VWT)(mm) and percent wall volume(PWV)(%) .	Measured at Baseline, 1, 3 months
Change in MVE, as assessed by CEUS	The changes in normalised maximal video-intensity enhancement (MVE) are calculated to quantify the density of IPN as assessed by CEUS.	Measured at Baseline, 1, 3 months
Change in peak flow velocity, as assessed by doppler ultrasound	The changes of the systolic and diastolic peak flow velocity of the affected segments by doppler ultrasound.	Measured at Baseline, 1, 3 months
MACCE	incidence of major adverse cardiovascular and cerebrovascular events(MACCE)	Measured at Baseline, 1, 3 months
Incidence of adverse events	Allergic to sunshine,hepatic or renal dysfunction,thyroid dysfunction	Measured at Baseline, 1, 3 months
Lipid change	To evaluate the change in lipid and lipoprotein levels as assessed by percentage change from baseline.	Measured at Baseline, 1, 3 months

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Harbin Medical University
• Collaborators: Tsinghua University
• Investigators: Study Chair: TIAN YE, First Affiliated Hospital of Harbin Medical University

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2023
• Primary Completion (Actual): September 20, 2023
• Study Completion (Actual): September 20, 2023

Study Registration Dates

• First Submitted: December 4, 2017
• First Submitted That Met QC Criteria: December 18, 2017
• First Posted (Actual): December 22, 2017

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pathological Conditions, Anatomical; Carotid Artery Diseases; Atherosclerosis; Plaque, Atherosclerotic
• Other Study ID Numbers: Ye Tian carotid

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No