Back to resultsSonodynamic Therapy on Patients With Femoropopliteal PAD and Claudication
Primary Purpose
Peripheral Arterial Disease, Atherosclerosis, Cardiovascular Diseases
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Optimal Medical Care
Sonodynamic therapy
Sponsored by
About this trial
This is an interventional treatment trial for Peripheral Arterial Disease
Eligibility Criteria
Inclusion Criteria:
- Patients with atherosclerotic peripheral artery disease with symptoms of moderate to severe intermittent claudication (defined as ability to walk at least 2, but not more than 11, minutes on a graded treadmill test using the Gardner protocol)
- Aged ≥40 years
- Resting ABI < 0.9 or ABI decreases > 0.15 after treadmill test regardless of the ABI at rest
- Presence of significant stenosis but not occlusion of femoropopliteal arteries including the common femoral artery, superficial femoral artery and popliteal artery as determined by: Duplex ultrasound imaging OR lower extremity computed Tomography Angiography (CTA) OR lower extremity magnetic resonance angiography (MRA) OR lower extremity catheter-based contrast arteriography. Each of these noninvasive and invasive anatomic assessments will identify patients with at least a 50% stenosis in the affected segment
- Stable use of low to moderate dose statin and the permitted statin drugs/doses: atorvastatin 20 mg, simvastatin 40 mg, rosuvastatin 10 mg, pravastatin, 40 mg, fluvastatin 80 mg or lovastatin 40 mg for at least 6 weeks prior to screening
- Written informed consent
Exclusion Criteria:
- Critical limb ischemia or other comorbid conditions that limit walking ability (claudication must be the consistent primary exercise limitation)
- Inability to complete treadmill testing per protocol requirements
- Two treadmill tests are completed at baseline to confirm reproducibility of results; those who deviates >25% are excluded
- Severe aorto-iliac arteries stenosis or occlusion documented by noninvasive and invasive anatomic assessments
- Allergic to DVDMS
- Diagnosis of porphyria
- Pregnant women and nursing mothers
- Contraindications of PET/CT
- Concurrent enrollment in another clinical trial
- Presence of any clinical condition that in the opinion of the principal Investigator or the sponsor makes the patient not suitable to participate in the trial
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Optimal Medical Care
Optimal Medical Care and SDT
Arm Description
Optimal medical care (OMC) only is administrated in this arm. OMC is established according to the standards established by the 2016 ACC-AHA Guidelines for the Management of Patients with Peripheral Artery Disease in order to promote best practices for risk factor management.
OMC and sonodynamic therapy (SDT) are administrated in this arm.
Outcomes
Primary Outcome Measures
PWT change, mins
Change from baseline peak walking time (PWT) at 6 months is assessed by graded treadmill test (Gardner protocol). The patient continues the test until walking can no longer be tolerated because of claudication symptoms.
MDS TBR change, (%)
Change from baseline most disease segments (MDS) at 3 months is assessed by 18FDG-PET imaging. Uptake of FDG by the common and superficial femoral artery is expressed as the target, vessel wall to background, lumen ratio (TBR). The mean max MDS TBR is defined as the arterial segment centered on the slice of artery demonstrating the highest FDG uptake at baseline within the index vessel, and calculated as a mean of maximum TBR values derived from three contiguous axial segments.
Secondary Outcome Measures
COT change, mins
Change from baseline claudication onset time (COT) at 6 months is assessed by graded treadmill test (Gardner protocol). The patient continues the test until calf muscle discomfort is first noticed.
AS TBR change, (%)
Change from baseline active slice (AS) at 3 months is assessed by 18FDG-PET imaging. Uptake of FDG by the common and superficial femoral artery is expressed as the target, vessel wall to background, lumen ratio (TBR). The mean max AS TBR is defined as average mean maximal TBR of only slices with TBR >1.6 from index vessel at baseline.
WV TBR change, (%)
Change from baseline whole vessel (WV) TBR at 3 months is assessed by 18FDG-PET imaging. Uptake of FDG by the common and superficial femoral artery is expressed as the target, vessel wall to background, lumen ratio (TBR). The mean max WV TBR is defined as a single whole vessel average mean maximal TBR of all the slices that compose the index vessel.
Serum inflammation cytokine level
Including Interleukin-6, Interleukin-1β, and high-sensitivity C-reactive protein (hs-CRP) level in serum
Pre-exercise ABI
Ankle-Brachial Index (ABI) is the ratio of the blood pressure at the ankle to the blood pressure of the upper arm. Pre-exercise ABI is collected routinely with the patient supine immediately prior to a treadmill test.
Post-exercise ABI
Ankle-Brachial Index (ABI) is the ratio of the blood pressure at the ankle to the blood pressure of the upper arm. Post-exercise ABI is collected routinely with the patient supine immediately following a treadmill test.
Intimal-medial thickness, (mm)
Estimation of the intimal-medial thickness for common femoral artery by doppler ultrasound.
Peak flow velocity, (cm/s)
Estimation of the systolic and diastolic peak flow velocity of the affected segments by doppler ultrasound.
Vessels' diameter, (mm)
Estimation of the vessels' diameter for common femoral artery by doppler ultrasound.
Diameter stenosis, (%)
Estimation of the maximum diameter stenosis of the affected segments by doppler ultrasound.
WIQ score
The Walking Impairment Questionnaire (WIQ) assesses the severity of the subjective walking impairment on distance, speed, and stair climbing scales. It is administered as a self report. Range: Minimum score is 0.2, maximum 100.
SF-36 score
The patient reported SF-36 data assesses subjective physical limitations, leg symptoms, social function, treatment satisfaction, and quality of life. It is administered as a self report. Higher scores are indicative of better outcome. The summary scores is compiled by taking the mean of five subscales generated from the original questions. Range: Minimum score is 11.1, maximum 85.
Full Information
NCT ID
NCT03318484
First Posted
October 12, 2017
Last Updated
August 17, 2021
Sponsor
First Affiliated Hospital of Harbin Medical University
Collaborators
Harbin Medical University
1. Study Identification
Unique Protocol Identification Number
NCT03318484
Brief Title
Sonodynamic Therapy on Patients With Femoropopliteal PAD and Claudication
Official Title
Sonodynamic Therapy Manipulate Atherosclerosis Regression Trial Among Patients With Femoropopliteal PAD and Claudication
Study Type
Interventional
2. Study Status
Record Verification Date
October 2017
Overall Recruitment Status
Withdrawn
Why Stopped
Re-registered
Study Start Date
November 2017 (Anticipated)
Primary Completion Date
November 2019 (Anticipated)
Study Completion Date
November 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
First Affiliated Hospital of Harbin Medical University
Collaborators
Harbin Medical University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The purpose of this trial is to evaluate the safety and efficacy of sonodynamic therapy (SDT) in reducing atherosclerotic plaques inflammation and increasing peak walking time (PWT) among peripheral artery disease (PAD) patients with symptom of intermittent claudication.
Detailed Description
Atherosclerotic lower extremity PAD affects more than 20 million people in the world. PAD is associated with a major decline in functional status and claudication is the most frequent symptom. Current claudication therapies are associated with significant limitations. Pharmacotherapy cilostazol and supervised exercise are recommended in 2016 AHA/ACC Guideline on the management of lower extremity PAD patients with claudication, but cilostazol may not achieve an ideal response rate, and supervised exercise efficacy may be limited by co-morbidities and medicare reimburse. Furthermore endovascular procedure may not be feasible, durable or cost-effective, especially in femoropopliteal arteries.
The aim of this trial is to test the hypothesis that SDT improves PWT by inhibiting atherosclerotic plaques inflammation in femoropopliteal arteries PAD patients compared to optimal medical care (OMC) within 6 month. An estimated 80 eligible patients will be randomly divided into tow groups: OMC and SDT combined with OMC. Recruitment will be performed over 6 months and patients will be followed for 6 months; the anticipated total study duration will be 2 years.
Finally, this trial investigate the safety and efficacy of SDT in PAD patients with intermittent claudication and explore new end-points to evaluate therapeutic effects using PET-CT imaging as well as traditional endpoints.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peripheral Arterial Disease, Atherosclerosis, Cardiovascular Diseases
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Optimal Medical Care
Arm Type
Active Comparator
Arm Description
Optimal medical care (OMC) only is administrated in this arm. OMC is established according to the standards established by the 2016 ACC-AHA Guidelines for the Management of Patients with Peripheral Artery Disease in order to promote best practices for risk factor management.
Arm Title
Optimal Medical Care and SDT
Arm Type
Experimental
Arm Description
OMC and sonodynamic therapy (SDT) are administrated in this arm.
Intervention Type
Drug
Intervention Name(s)
Optimal Medical Care
Intervention Description
Aspirin 100mg once a day, Atorvastatin 20mg once a day and Antihypertensive Agents if necessary.
Intervention Type
Combination Product
Intervention Name(s)
Sonodynamic therapy
Intervention Description
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 1.8W/cm2 for femoral lesions, resonance frequency: 1.0 MHz and duty factor: 30%.
Primary Outcome Measure Information:
Title
PWT change, mins
Description
Change from baseline peak walking time (PWT) at 6 months is assessed by graded treadmill test (Gardner protocol). The patient continues the test until walking can no longer be tolerated because of claudication symptoms.
Time Frame
Measured at baseline, 1, 3 and 6 months.
Title
MDS TBR change, (%)
Description
Change from baseline most disease segments (MDS) at 3 months is assessed by 18FDG-PET imaging. Uptake of FDG by the common and superficial femoral artery is expressed as the target, vessel wall to background, lumen ratio (TBR). The mean max MDS TBR is defined as the arterial segment centered on the slice of artery demonstrating the highest FDG uptake at baseline within the index vessel, and calculated as a mean of maximum TBR values derived from three contiguous axial segments.
Time Frame
Measured at baseline, 1 and 3 months.
Secondary Outcome Measure Information:
Title
COT change, mins
Description
Change from baseline claudication onset time (COT) at 6 months is assessed by graded treadmill test (Gardner protocol). The patient continues the test until calf muscle discomfort is first noticed.
Time Frame
Measured at baseline, 1, 3, and 6 months.
Title
AS TBR change, (%)
Description
Change from baseline active slice (AS) at 3 months is assessed by 18FDG-PET imaging. Uptake of FDG by the common and superficial femoral artery is expressed as the target, vessel wall to background, lumen ratio (TBR). The mean max AS TBR is defined as average mean maximal TBR of only slices with TBR >1.6 from index vessel at baseline.
Time Frame
Measured at baseline, 1 and 3 months.
Title
WV TBR change, (%)
Description
Change from baseline whole vessel (WV) TBR at 3 months is assessed by 18FDG-PET imaging. Uptake of FDG by the common and superficial femoral artery is expressed as the target, vessel wall to background, lumen ratio (TBR). The mean max WV TBR is defined as a single whole vessel average mean maximal TBR of all the slices that compose the index vessel.
Time Frame
Measured at baseline, 1 and 3 months.
Title
Serum inflammation cytokine level
Description
Including Interleukin-6, Interleukin-1β, and high-sensitivity C-reactive protein (hs-CRP) level in serum
Time Frame
Measured at baseline, 1, 3, and 6 months.
Title
Pre-exercise ABI
Description
Ankle-Brachial Index (ABI) is the ratio of the blood pressure at the ankle to the blood pressure of the upper arm. Pre-exercise ABI is collected routinely with the patient supine immediately prior to a treadmill test.
Time Frame
Measured at baseline, 1, 3, and 6 months.
Title
Post-exercise ABI
Description
Ankle-Brachial Index (ABI) is the ratio of the blood pressure at the ankle to the blood pressure of the upper arm. Post-exercise ABI is collected routinely with the patient supine immediately following a treadmill test.
Time Frame
Measured at baseline, 1, 3, and 6 months.
Title
Intimal-medial thickness, (mm)
Description
Estimation of the intimal-medial thickness for common femoral artery by doppler ultrasound.
Time Frame
Measured at baseline, 1, 3, and 6 months.
Title
Peak flow velocity, (cm/s)
Description
Estimation of the systolic and diastolic peak flow velocity of the affected segments by doppler ultrasound.
Time Frame
Measured at baseline, 1, 3, and 6 months.
Title
Vessels' diameter, (mm)
Description
Estimation of the vessels' diameter for common femoral artery by doppler ultrasound.
Time Frame
Measured at baseline, 1, 3, and 6 months.
Title
Diameter stenosis, (%)
Description
Estimation of the maximum diameter stenosis of the affected segments by doppler ultrasound.
Time Frame
Measured at baseline, 1, 3, and 6 months.
Title
WIQ score
Description
The Walking Impairment Questionnaire (WIQ) assesses the severity of the subjective walking impairment on distance, speed, and stair climbing scales. It is administered as a self report. Range: Minimum score is 0.2, maximum 100.
Time Frame
Measured at baseline, 1, 3, and 6 months.
Title
SF-36 score
Description
The patient reported SF-36 data assesses subjective physical limitations, leg symptoms, social function, treatment satisfaction, and quality of life. It is administered as a self report. Higher scores are indicative of better outcome. The summary scores is compiled by taking the mean of five subscales generated from the original questions. Range: Minimum score is 11.1, maximum 85.
Time Frame
Measured at baseline, 1, 3, and 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with atherosclerotic peripheral artery disease with symptoms of moderate to severe intermittent claudication (defined as ability to walk at least 2, but not more than 11, minutes on a graded treadmill test using the Gardner protocol)
Aged ≥40 years
Resting ABI < 0.9 or ABI decreases > 0.15 after treadmill test regardless of the ABI at rest
Presence of significant stenosis but not occlusion of femoropopliteal arteries including the common femoral artery, superficial femoral artery and popliteal artery as determined by: Duplex ultrasound imaging OR lower extremity computed Tomography Angiography (CTA) OR lower extremity magnetic resonance angiography (MRA) OR lower extremity catheter-based contrast arteriography. Each of these noninvasive and invasive anatomic assessments will identify patients with at least a 50% stenosis in the affected segment
Stable use of low to moderate dose statin and the permitted statin drugs/doses: atorvastatin 20 mg, simvastatin 40 mg, rosuvastatin 10 mg, pravastatin, 40 mg, fluvastatin 80 mg or lovastatin 40 mg for at least 6 weeks prior to screening
Written informed consent
Exclusion Criteria:
Critical limb ischemia or other comorbid conditions that limit walking ability (claudication must be the consistent primary exercise limitation)
Inability to complete treadmill testing per protocol requirements
Two treadmill tests are completed at baseline to confirm reproducibility of results; those who deviates >25% are excluded
Severe aorto-iliac arteries stenosis or occlusion documented by noninvasive and invasive anatomic assessments
Allergic to DVDMS
Diagnosis of porphyria
Pregnant women and nursing mothers
Contraindications of PET/CT
Concurrent enrollment in another clinical trial
Presence of any clinical condition that in the opinion of the principal Investigator or the sponsor makes the patient not suitable to participate in the trial
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
YE TIAN, MD, PhD
Organizational Affiliation
First Affiliated Hospital of Harbin Medical University
Official's Role
Study Chair
12. IPD Sharing Statement
Learn more about this trial
Sonodynamic Therapy on Patients With Femoropopliteal PAD and Claudication
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