Peripheral Arterial DiseasePhase 1/2NCT03318484
Sonodynamic Therapy on Patients With Femoropopliteal PAD and Claudication
A Phase 1/2 study testing Optimal Medical Care and Sonodynamic therapy in people with Peripheral Arterial Disease and Atherosclerosis, run by First Affiliated Hospital of Harbin Medical University.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Peripheral Arterial Disease, Atherosclerosis, Cardiovascular Diseases
- What is being tested?
- Optimal Medical Care and Sonodynamic therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Nov 2017to Nov 2019
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
About this study
Official title: Sonodynamic Therapy Manipulate Atherosclerosis Regression Trial Among Patients With Femoropopliteal PAD and Claudication
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.
Read the 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.
- Being tested
- Optimal Medical Care, Sonodynamic therapy
- Medical subject headings
- Peripheral Arterial Disease, Atherosclerosis, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Optimal Medical CareDrug
Aspirin 100mg once a day, Atorvastatin 20mg once a day and Antihypertensive Agents if necessary.
Sonodynamic therapyCombination product
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%.
| Study group | Role | What they receive |
|---|---|---|
| Optimal Medical Care | Active comparator | 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. Receives: Drug: Optimal Medical Care |
| Optimal Medical Care and SDT | Experimental | OMC and sonodynamic therapy (SDT) are administrated in this arm. Receives: Drug: Optimal Medical Care; Combination Product: Sonodynamic therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Measured at baseline, 1, 3 and 6 months.
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.
Measured: Measured at baseline, 1 and 3 months.
Secondary outcomes (12)
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.
Measured: Measured at baseline, 1, 3, and 6 months.
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.
Measured: Measured at baseline, 1 and 3 months.
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.
Measured: Measured at baseline, 1 and 3 months.
Serum inflammation cytokine level
Including Interleukin-6, Interleukin-1β, and high-sensitivity C-reactive protein (hs-CRP) level in serum
Measured: Measured at baseline, 1, 3, and 6 months.
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.
Measured: Measured at baseline, 1, 3, and 6 months.
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.
Measured: Measured at baseline, 1, 3, and 6 months.
Intimal-medial thickness, (mm)
Estimation of the intimal-medial thickness for common femoral artery by doppler ultrasound.
Measured: Measured at baseline, 1, 3, and 6 months.
Peak flow velocity, (cm/s)
Estimation of the systolic and diastolic peak flow velocity of the affected segments by doppler ultrasound.
Measured: Measured at baseline, 1, 3, and 6 months.
Vessels' diameter, (mm)
Estimation of the vessels' diameter for common femoral artery by doppler ultrasound.
Measured: Measured at baseline, 1, 3, and 6 months.
Diameter stenosis, (%)
Estimation of the maximum diameter stenosis of the affected segments by doppler ultrasound.
Measured: Measured at baseline, 1, 3, and 6 months.
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.
Measured: Measured at baseline, 1, 3, and 6 months.
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.
Measured: Measured at baseline, 1, 3, and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2017
- Study startNov 2017 (estimated)
- Primary completionNov 2019 (estimated)
- Study completionNov 2019 (estimated)
Why it stopped: Re-registered
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Peripheral Arterial DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- First Affiliated Hospital of Harbin Medical University
- Sponsor type
- University, hospital or other
- Collaborators
- Harbin Medical University
- Responsible party
- Sponsor
- Investigators
- YE TIAN, MD, PhD, Study chair, First Affiliated Hospital of Harbin Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03318484
- Sponsor's protocol ID
- Ye Tian
- Status last verified
- Oct 2017
- First submitted
- 12 Oct 2017
- Last updated
- 23 Aug 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sonodynamic Therapy Manipulate Atherosclerosis Regression Trial Among Patients With Femoropopliteal PAD and Claudication
- ClinicalTrials.gov ID
- NCT03318484
- Acronym / sponsor ID
- Ye Tian
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Re-registered
- Enrolment
- 0 participants (actual)
- Lead sponsor
- First Affiliated Hospital of Harbin Medical UniversityUniversity, hospital or other
- Collaborators
- Harbin Medical University
- Study start
- Nov 2017 (estimated)
- Primary completion
- Nov 2019 (estimated)
- Study completion
- Nov 2019 (estimated)
- First posted
- 24 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Optimal Medical Care | Active comparator | Drug: Optimal Medical CareOptimal 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. |
| Optimal Medical Care and SDT | Experimental | Drug: Optimal Medical Care, Combination Product: Sonodynamic therapyOMC and sonodynamic therapy (SDT) are administrated in this arm. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Optimal Medical CareAspirin 100mg once a day, Atorvastatin 20mg once a day and Antihypertensive Agents if necessary. | Drug | Optimal Medical Care, Optimal Medical Care and SDT |
| Sonodynamic therapySDT 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%. | Combination product | Optimal Medical Care and SDT |
Primary outcome
PWT change, mins
Time frame: Measured at baseline, 1, 3 and 6 months.
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, (%)
Time frame: Measured at baseline, 1 and 3 months.
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.
12 secondary outcomes
COT change, mins
Time frame: Measured at baseline, 1, 3, and 6 months.
AS TBR change, (%)
Time frame: Measured at baseline, 1 and 3 months.
WV TBR change, (%)
Time frame: Measured at baseline, 1 and 3 months.
Serum inflammation cytokine level
Time frame: Measured at baseline, 1, 3, and 6 months.
Pre-exercise ABI
Time frame: Measured at baseline, 1, 3, and 6 months.
Post-exercise ABI
Time frame: Measured at baseline, 1, 3, and 6 months.
Intimal-medial thickness, (mm)
Time frame: Measured at baseline, 1, 3, and 6 months.
Peak flow velocity, (cm/s)
Time frame: Measured at baseline, 1, 3, and 6 months.
Vessels' diameter, (mm)
Time frame: Measured at baseline, 1, 3, and 6 months.
Diameter stenosis, (%)
Time frame: Measured at baseline, 1, 3, and 6 months.
WIQ score
Time frame: Measured at baseline, 1, 3, and 6 months.
SF-36 score
Time frame: Measured at baseline, 1, 3, and 6 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
YE TIAN, MD, PhD study chair
First Affiliated Hospital of Harbin Medical University
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Optimal Medical Care and Sonodynamic therapy in people with Peripheral Arterial Disease and Atherosclerosis, run by First Affiliated Hospital of Harbin Medical University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 23 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PWT change, mins (time frame: Measured at baseline, 1, 3 and 6 months.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2021.