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

Carotid Atherosclerosis Clinical Trial

— SMART-C  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03382249
• Other study ID #: Ye Tian carotid
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: September 20, 2023
• Est. completion date: September 20, 2023

Study information

• Verified date: September 2023
• Source: First Affiliated Hospital of Harbin Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 20, 2023
• Est. primary completion date: September 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Atherosclerosis
• Carotid Artery Diseases
• Carotid Atherosclerosis
• Plaque, Atherosclerotic

Intervention

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

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang

Sponsors (2)

Lead Sponsor	Collaborator
First Affiliated Hospital of Harbin Medical University	Tsinghua University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Change in calcification volume, as assessed by MRI	The changes in calcification volume as assessed by MRI.	Measured at Baseline, 1, 3 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	MACCE	incidence of major adverse cardiovascular and cerebrovascular events(MACCE)	Measured at Baseline, 1, 3 months
Secondary	Incidence of adverse events	Allergic to sunshine,hepatic or renal dysfunction,thyroid dysfunction	Measured at Baseline, 1, 3 months
Secondary	Lipid change	To evaluate the change in lipid and lipoprotein levels as assessed by percentage change from baseline.	Measured at Baseline, 1, 3 months