Autologous BMMNC Combined With HA Therapy for PAOD

Critical Limb Ischemia Clinical Trial

Official title:

Therapeutic Angiogenesis for Peripheral Artery Occlusive Disease Using Hyaluronan Combined With Autologous Bone Marrow Cell Therapy -- Phase I/II Safety and Efficacy Study

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03214887
• Other study ID #: AS-IRB-BM-14056
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: January 17, 2017
• Est. completion date: July 27, 2018

Study information

• Verified date: March 2022
• Source: Academia Sinica, Taiwan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and efficacy of hyaluronan combined with autologous bone marrow mononuclear cells for the treatment of critical PAOD patients.

Description:

This is a multicenter, non-blinded and randomized study to evaluate the safety and efficacy of hyaluronan (HA) combined with autologous bone marrow mononuclear cells (BMMNC) therapy for critical peripheral arterial occlusive disease (PAOD) patients.

A total of 30 subjects will be recruited into the study. The subjects will be randomized into 3 different arms. During the Phase I study, 9 subjects recruited while another 21 additional subjects will be recruited in Phase II after the review of DSMB and consultation of Taiwan FDA on the results of the Phase I study.

Each subject will be administered 5~10 injections of RV-P1501, the number of injections depends on the size of the subject's ischemic leg. Each subject will receive treatment once. Subjects will be assigned to the treatments in random order. Evaluations including ABI, PWT/PFWT, clinical status, EF, CTA, biochemistry and hematology checked during the inclusion and exclusion evaluation, and will be taken at baseline, 1 week, 2 weeks, 4 weeks, 12 weeks, and 24 weeks after the treatment.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: July 27, 2018
• Est. primary completion date: June 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Patient age = 20

• Patients with severe PAOD and diagnosed with Rutherford category 3, 4, or 5

• Contraindication to angioplasty or bypass surgery, or post-angioplasty or bypass surgery for once but with limited or no effect.

• Patient without hypertension or hypertensive patient with adequate-controlled blood pressure.

• With signed informed consent

Exclusion Criteria:

• Patient undergone any organ transplantation

• Inability to undergo bone marrow aspiration

• Pregnant woman

• Life expectancy < 1 year

• Cognitive impairment

• Active malignancy in 5 years prior to treatment

• Bleeding diathesis or pulmonary embolism

• Patient with active major cardiovascular diseases such as unstable angina, arrhythmia, heart failure, impaired cardiac function (ejection fraction < 45%), or stroke

• Estimated Glomerular Filtration Rate (eGFR) < 30

• Glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) values higher than 80 U/L

• Patient with severe diabetes mellitus (HbA1C > 8%)

• Patient with alcohol addiction

• Patient with drug abuse

• Patient with infections or skin disease on the ischemic leg.

• Allergic to HA

• Patient whose blockage region only occurred in the femoral artery or at foot.

Related Conditions & MeSH terms

• Arterial Occlusive Diseases
• Critical Limb Ischemia
• Ischemia
• Peripheral Arterial Occlusive Disease

Intervention

Biological:
• RV-P1501
Gel-like product with BMMNCs in each ml of hyaluronan (HA) solution

Locations

Country	Name	City	State
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (3)

Lead Sponsor	Collaborator
Academia Sinica, Taiwan	National Cheng-Kung University Hospital, National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ankle Brachial Index (ABI)	The percentage change of ABI from 3 follow-ups with the baseline.	Day 0, Week 4, Week 12, Week 24
Secondary	Clinical status (Rutherford category)	Improvement in Rutherford scale was recorded at baseline and each follow-up.	Day 0, Week 1, Week 2, Week 4, Week 12, Week 24
Secondary	Level of pain at rest	Rest pain was measured using Wong-Baker FACES pain rating scale at baseline and each follow-up visit.	Day 0, Week 1, Week 2, Week 4, Week 12, Week 24
Secondary	Ulcer size in cm2	Ulcer size was assessed and measured at each follow-up interval and compared to baseline.	Day 0, Week 1, Week 2, Week 4, Week 12, Week 24
Secondary	Ulcer category	Ulcer status was assessed at each follow-up interval and compared to baseline.	Day 0, Week 1, Week 2, Week 4, Week 12, Week 24
Secondary	PWT/PFWT in seconds	Peak walking time and pain-free walking time was measured at baseline and compared to W4, W12 and W24 by treadmill walking tests.	Day 0, Week 4, Week 12, Week 24
Secondary	Amputation free	Time to below the knee amputation of the ipsilateral leg after the treatment.	Week 1, Week 2, Week 4, Week 12, Week 24
Secondary	Ejection fraction	Ejection fraction was measured by echocardiogram to record the cardiac function at W12 and W24.	Week 12, Week 24
Secondary	CT angiography	CT angiography was performed to record the morphology of blood vessel, location, and the vessel cross section percentage.	Week 12, Week 24
Secondary	Biochemistry	Biochemistry tests were performed to interpret the health assessment at W12 and W24.	Week 12, Week 24
Secondary	Hematology	Hematology tests were performed to interpret the health assessment at W12 and W24.	Week 12, Week 24