Sonodynamic Therapy in the Treatment of Carotid Atherosclerosis (SMART-C)

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

Sonodynamic therapy (SDT) is a new treatment for carotid atherosclerotic plaque. The purpose of this study is to evaluate the safety and initial effectiveness of this technique.

Study Overview

• Status: Completed
• Conditions: Carotid Atherosclerosis
• Intervention / Treatment: Combination product: Sonodynamic therapy (SDT)

Detailed Description

Carotid atherosclerotic plaque is an important cause of ischemic stroke. 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 purpose of this trial is to evaluate the safety and initial effectiveness of SDT. The SDT can induce macrophage elimination and inhibit matrix degradation, which will promote plaque lipid depletion, inflammation level decrease and changes in other plaque tissue components, leading to plaque stabilization and reduction.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: 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
• 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
• Patient who is attending other clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Sonodynamic therapy(SDT); Sonodynamic therapy(SDT) treatment is the combination of sonosensitizer administration and target atherosclerotic lesions ultrasound exposure.

Combination product: Sonodynamic therapy (SDT); 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 MaxWT, as assessed by MRI	The changes in plaque MaxWT (maximum wall thickness) as assessed by MRI.	Measured at Baseline, 1, 3, 6, and 9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in IPH volume, as assessed by MRI	The changes in intraplaque hemorrhage (IPH) volume as assessed by MRI.	Measured at Baseline, 1, 3, 6, and 9 months
Change in LRNC volume, as assessed by MRI	The changes in LRNC (lipid-rich necrotic core) volume as assessed by MRI.	Measured at Baseline, 1, 3, 6, and 9 months
Change in plaque LM volume, as assessed by MRI	The changes in LM (loose matrix) volume as assessed by MRI.	Measured at Baseline, 1, 3, 6, and 9 months
Change in calcification volume, as assessed by MRI	The changes in calcification (CA) volume as assessed by MRI.	Measured at Baseline, 1, 3, 6, and 9 months
Change in plaque volume, as assessed by MRI	The changes in plaque volume(mm3) as assessed by MRI	Measured at Baseline, 1, 3, 6, and 9 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, 6, and 9 months
MACCE	incidence of major adverse cardiovascular and cerebrovascular events(MACCE)	Measured at Baseline, 1, 3, 6, and 9 months
Incidence of adverse events	Allergic to sunshine,hepatic or renal dysfunction,thyroid dysfunction	Measured at Baseline, 1, 3, 6, and 9 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2019
• Primary Completion (Actual): January 30, 2020
• Study Completion (Actual): January 30, 2020

Study Registration Dates

• First Submitted: March 8, 2019
• First Submitted That Met QC Criteria: March 10, 2019
• First Posted (Actual): March 12, 2019

Study Record Updates

• Last Update Posted (Actual): July 10, 2024
• Last Update Submitted That Met QC Criteria: July 9, 2024
• Last Verified: July 1, 2024

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; Carotid Artery Diseases; Atherosclerosis
• Other Study ID Numbers: SMART-C pilot

Drug and device information, study documents

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