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

NCT ID: NCT03382249

Last Updated: 2023-09-21

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-20
• Study Completion Date: 2023-09-20

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.

Conditions

Carotid Atherosclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

pseudo-SDT

Intervention Type: COMBINATION_PRODUCT

Pseudo-SDT combines saline injection and obstructed ultrasound exposure on targeted lesions to simulate real SDT progression.

OMC and SDT

OMC and sonodynamic therapy (SDT) are administrated in this arm.

Group Type: EXPERIMENTAL

Sonodynamic therapy (SDT)

Intervention Type: COMBINATION_PRODUCT

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%.

Interventions

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%.

Intervention Type: COMBINATION_PRODUCT

pseudo-SDT

Pseudo-SDT combines saline injection and obstructed ultrasound exposure on targeted lesions to simulate real SDT progression.

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tsinghua University

OTHER

Sponsor Role: collaborator

First Affiliated Hospital of Harbin Medical University

OTHER

Sponsor Role: lead

Responsible Party

Ye Tian

Professor, MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

TIAN YE

Role: STUDY_CHAIR

First Affiliated Hospital of Harbin Medical University

Locations

The First Affiliated Hospital of Harbin Medical University

Harbin, Heilongjiang, China

Countries

China

Other Identifiers

Ye Tian carotid

Identifier Type: -

Identifier Source: org_study_id