Sonodynamic Therapy on Patients With Femoropopliteal PAD and Claudication
Paraules clau
Resum
Descripció
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.
Dates
| Darrera verificació: | 09/30/2017 |
| Primer enviat: | 10/11/2017 |
| Inscripció estimada enviada: | 10/17/2017 |
| Publicat per primera vegada: | 10/23/2017 |
| Última actualització enviada: | 10/17/2017 |
| Publicació de l'última actualització: | 10/23/2017 |
| Data d'inici de l'estudi real: | 10/31/2017 |
| Data estimada de finalització primària: | 10/31/2019 |
| Data estimada de finalització de l’estudi: | 10/31/2019 |
Condició o malaltia
Intervenció / tractament
Drug: Optimal Medical Care
Combination Product: Optimal Medical Care and SDT
Fase
Grups de braços
| Braç | Intervenció / tractament |
|---|---|
| Active Comparator: Optimal Medical Care 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. | |
| Experimental: Optimal Medical Care and SDT OMC and sonodynamic therapy (SDT) are administrated in this arm. | Combination Product: Optimal Medical Care and SDT 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%. |
Criteris d'elegibilitat
| Edats elegibles per estudiar | 40 Years Per a 40 Years |
| Sexes elegibles per estudiar | All |
| Accepta voluntaris saludables | Sí |
| Criteris | Inclusion Criteria: 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 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 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 Exclusion Criteria: 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. Allergic to DVDMS 6. Diagnosis of porphyria 7. Pregnant women and nursing mothers 8. Contraindications of PET/CT 9. Concurrent enrollment in another clinical trial 10. 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 |
Resultat
Mesures de resultats primaris
1. PWT change, mins [Measured at baseline, 1, 3 and 6 months.]
2. MDS TBR change, (%) [Measured at baseline, 1 and 3 months.]
Mesures de resultats secundaris
1. COT change, mins [Measured at baseline, 1, 3, and 6 months.]
2. AS TBR change, (%) [Measured at baseline, 1 and 3 months.]
3. WV TBR change, (%) [Measured at baseline, 1 and 3 months.]
4. Serum inflammation cytokine level [Measured at baseline, 1, 3, and 6 months.]
5. Pre-exercise ABI [Measured at baseline, 1, 3, and 6 months.]
6. Post-exercise ABI [Measured at baseline, 1, 3, and 6 months.]
7. Intimal-medial thickness, (mm) [Measured at baseline, 1, 3, and 6 months.]
8. Peak flow velocity, (cm/s) [Measured at baseline, 1, 3, and 6 months.]
9. Vessels' diameter, (mm) [Measured at baseline, 1, 3, and 6 months.]
10. Diameter stenosis, (%) [Measured at baseline, 1, 3, and 6 months.]
11. WIQ score [Measured at baseline, 1, 3, and 6 months.]
12. SF-36 score [Measured at baseline, 1, 3, and 6 months]
