Peripheral Arterial DiseasePhase 1/2SMART-PADNCT03457662
Sonodynamic Therapy Manipulates Atherosclerosis Regression Trial on Patients With PAD and Claudication
A Phase 1/2 study testing OMC and pseudo-SDT and OMC and SDT in people with Peripheral Arterial Disease and Atherosclerosis, run by First Affiliated Hospital of Harbin Medical University at 1 site in China.
Trial summary
The purpose of this trial is to evaluate the safety and efficacy of sonodynamic therapy (SDT) on reducing atherosclerotic plaques inflammation among patients with symptomatic femoropopliteal peripheral artery disease. 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?
- OMC and pseudo-SDT and OMC and SDT
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteChina
- Study dates
- 15 Mar 2018to 11 Apr 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
- 1. 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)
- 2. Aged ≥40 years
- 3. Resting ABI < 0.9 or ABI decreases > 0.15 after treadmill test regardless of the ABI at rest
- 4. Presence of atherosclerotic plaque in 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
- 5. 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
- 6. Written informed consent
Who cannot join
- 1. Critical limb ischemia or other comorbid conditions that limit walking ability (claudication must be the consistent primary exercise limitation)
- 2. Inability to complete treadmill testing per protocol requirements
- 3. Two treadmill tests are completed at baseline to confirm reproducibility of results; those who deviates >25% are excluded
- 4. Severe aorto-iliac arteries stenosis or occlusion documented by noninvasive and invasive anatomic assessments
- 5. Active systemic inflammatory disease or have an infectious disease within 1 month prior to enrollment
- 6. Allergic to DVDMS
Show all 11Show fewer
- 7. Diagnosis of porphyria
- 8. Pregnant women and nursing mothers
- 9. Contraindications of PET/CT
- 10. Concurrent enrollment in another clinical trial
- 11. Presence of any clinical condition that in the opinion of the principal investigator makes the patient not suitable to participate in the trial
Trial locations and contacts
1 site in 1 country.
China1 site
The First Affiliated Hospital of Harbin Medical University
Harbin, Heilongjiang, 150000
About this study
The purpose of this trial is to evaluate the safety and efficacy of sonodynamic therapy (SDT) on reducing atherosclerotic plaques inflammation among patients with symptomatic femoropopliteal peripheral artery disease.
Read the detailed description
Atherosclerotic lower extremity PAD affects more than 202 million people in the worldwide. PAD is associated with a major decline in walking 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.
SDT is a novel anti-inflammatory regimen to atherosclerosis with non-invasive, plaque-based, macrophage-targeted characteristics. We hypothesize that reducing local arterial inflammation of affected limb will ameliorate claudication symptom in patients with PAD. The main objectives of this trial are to evaluate the efficacy and safety of SDT in patients with symptomatic femoropopliteal PAD.
Thirty-two eligible participants will be randomly assigned to SDT or sham-control groups. Results of PET/CT are the prespecified primary endpoint.
- Being tested
- OMC and pseudo-SDT, OMC and SDT
- 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.
OMC and pseudo-SDTCombination product
OMC is established according to the 2016 ACC-AHA Guidelines for the Management of Patients with PAD. Pseudo-SDT combines saline injection and obstructed ultrasound exposure on targeted lesions to simulate real SDT progression.
OMC and SDTCombination product
OMC is established according to the 2016 ACC-AHA Guidelines for the Management of Patients with PAD. 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 of each lesion.
| Study group | Role | What they receive |
|---|---|---|
| OMC and pseudo-SDT | Active comparator | Optimal medical care (OMC) and pseudo-SDT are 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: Combination Product: OMC and pseudo-SDT |
| OMC and SDT | Experimental | OMC and SDT are administrated in this arm. Receives: Combination Product: OMC and SDT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in MDS TBR
The primary efficacy endpoint is the change of target-to-background ratio (TBR) within the most diseased segment (MDS) of index-leg artery at 30-day follow-up after treatment, defined as ratio of the standardized uptake value (SUV) in artery wall to background venous activity within the MDS of index- leg artery assessed by PET/CT.
Measured: Measured at baseline, 1month.
Secondary outcomes (8)
AS TBR change, (%)
Change from baseline to 30-day in active slice (AS) assessed by PET/CT. The mean max AS TBR is defined as average mean maximal TBR of only slices with TBR >1.6 from index-leg at baseline.
Measured: Measured at baseline, 1month.
WV TBR change, (%)
Change from baseline to 30-day in whole vessel (WV) TBR assessed by PET/CT. 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, 1month.
PWT change, s
Change from baseline peak walking time (PWT) at 1 month 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, 1month.
COT change, s
Change from baseline claudication onset time (COT) at 1 month is assessed by graded treadmill test (Gardner protocol). The patient continues the test until calf muscle discomfort is first noticed.
Measured: Measured at baseline, 1month.
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, 1month.
Diameter stenosis, (%)
Estimation of the maximum diameter stenosis of the affected segments by doppler ultrasound.
Measured: Measured at baseline, 1month.
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, 1month.
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, 1month.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2018
- Study start15 Mar 2018
- Primary completion18 Dec 2018
- Study completion11 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- First Affiliated Hospital of Harbin Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ye Tian, First Affiliated Hospital of Harbin Medical University
- Investigators
- YE TIAN, MD, PhD, Study chair, First Affiliated Hospital of Harbin Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03457662
- Sponsor's protocol ID
- Ye Tian PAD
- Acronym
- SMART-PAD
- Status last verified
- Aug 2024
- First submitted
- 1 Mar 2018
- Last updated
- 21 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Jiang Y, Fan J, Li Y, Wu G, Wang Y, Yang J, Wang M, Cao Z, Li Q, Wang H, Zhang Z, Wang Y, Li B, Sun F, Zhang H, Zhang Z, Li K, Tian Y. Rapid reduction in plaque inflammation by sonodynamic therapy inpatients with symptomatic femoropopliteal peripheral artery disease:A randomized controlled trial. Int J Cardiol. 2021 Feb 15;325:132-139. doi: 10.1016/j.ijcard.2020.09.035. Epub 2020 Sep 20.
PubMed 32966832
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sonodynamic Therapy Manipulates Atherosclerosis Regression Trial on Patients With PAD and Claudication
- ClinicalTrials.gov ID
- NCT03457662
- Acronym / sponsor ID
- SMART-PAD / Ye Tian PAD
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- First Affiliated Hospital of Harbin Medical UniversityUniversity, hospital or other
- Study start
- 15 Mar 2018 (actual)
- Primary completion
- 18 Dec 2018 (actual)
- Study completion
- 11 Apr 2019 (actual)
- First posted
- 7 Mar 2018 (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) on reducing atherosclerotic plaques inflammation among patients with symptomatic femoropopliteal peripheral artery disease.
Detailed description
Atherosclerotic lower extremity PAD affects more than 202 million people in the worldwide. PAD is associated with a major decline in walking 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.
SDT is a novel anti-inflammatory regimen to atherosclerosis with non-invasive, plaque-based, macrophage-targeted characteristics. We hypothesize that reducing local arterial inflammation of affected limb will ameliorate claudication symptom in patients with PAD. The main objectives of this trial are to evaluate the efficacy and safety of SDT in patients with symptomatic femoropopliteal PAD.
Thirty-two eligible participants will be randomly assigned to SDT or sham-control groups. Results of PET/CT are the prespecified primary endpoint.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| OMC and pseudo-SDT | Active comparator | Combination Product: OMC and pseudo-SDTOptimal medical care (OMC) and pseudo-SDT are 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 SDT | Experimental | Combination Product: OMC and SDTOMC and 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)
- 1. 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)
- 2. Aged ≥40 years
- 3. Resting ABI < 0.9 or ABI decreases > 0.15 after treadmill test regardless of the ABI at rest
- 4. Presence of atherosclerotic plaque in 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
- 5. 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 (11 listed)
- 1. Critical limb ischemia or other comorbid conditions that limit walking ability (claudication must be the consistent primary exercise limitation)
- 2. Inability to complete treadmill testing per protocol requirements
- 3. Two treadmill tests are completed at baseline to confirm reproducibility of results; those who deviates >25% are excluded
- 4. Severe aorto-iliac arteries stenosis or occlusion documented by noninvasive and invasive anatomic assessments
- 5. Active systemic inflammatory disease or have an infectious disease within 1 month prior to enrollment
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 |
|---|---|---|
| OMC and pseudo-SDTOMC is established according to the 2016 ACC-AHA Guidelines for the Management of Patients with PAD. Pseudo-SDT combines saline injection and obstructed ultrasound exposure on targeted lesions to simulate real SDT progression. | Combination product | OMC and pseudo-SDT |
| OMC and SDTOMC is established according to the 2016 ACC-AHA Guidelines for the Management of Patients with PAD. 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 of each lesion. | Combination product | OMC and SDT |
Primary outcome
Change in MDS TBR
Time frame: Measured at baseline, 1month.
The primary efficacy endpoint is the change of target-to-background ratio (TBR) within the most diseased segment (MDS) of index-leg artery at 30-day follow-up after treatment, defined as ratio of the standardized uptake value (SUV) in artery wall to background venous activity within the MDS of index- leg artery assessed by PET/CT.
8 secondary outcomes
AS TBR change, (%)
Time frame: Measured at baseline, 1month.
WV TBR change, (%)
Time frame: Measured at baseline, 1month.
PWT change, s
Time frame: Measured at baseline, 1month.
COT change, s
Time frame: Measured at baseline, 1month.
Pre-exercise ABI
Time frame: Measured at baseline, 1month.
Diameter stenosis, (%)
Time frame: Measured at baseline, 1month.
WIQ score
Time frame: Measured at baseline, 1month.
SF-36 score
Time frame: Measured at baseline, 1month.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2024.
- Derived from this study: PubMed 32966832Jiang Y, Fan J, Li Y, Wu G, Wang Y, Yang J, Wang M, Cao Z, Li Q, Wang H, Zhang Z, Wang Y, Li B, Sun F, Zhang H, Zhang Z, Li K, Tian Y. Rapid reduction in plaque inflammation by sonodynamic therapy inpatients with symptomatic femoropopliteal peripheral artery disease:A randomized controlled trial. Int J Cardiol. 2021 Feb 15;325:132-139. doi: 10.1016/j.ijcard.2020.09.035. Epub 2020 Sep 20.
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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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing OMC and pseudo-SDT and OMC and SDT in people with Peripheral Arterial Disease and Atherosclerosis, run by First Affiliated Hospital of Harbin Medical University at 1 site in China.
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 11 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: finished, as of the sponsor's last update on 21 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in MDS TBR (time frame: Measured at baseline, 1month.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03457662, which also lists 1 linked publication.
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 21 Aug 2024.