Clinical trial NCT03214887: Autologous BMMNC Combined With HA Therapy for PAOD
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Peripheral Arterial Occlusive Disease
Critical Limb Ischemia
Keywords: Hyaluronan
Bone marrow mononuclear cells
Lead sponsor: Academia Sinica, Taiwan
Sponsor class: OTHER
Collaborators: name: National Taiwan University Hospital
name: National Cheng-Kung University Hospital
First posted: 2017-07-12
Enrollment: 0
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: RV-P1501-4: Gel-like product with 10 thousand BMMNCs in each ml of 1% hyaluronan (HA) solution

RV-P1501-5: Gel-like product with 100 thousand BMMNCs in each ml of 1% hyaluronan (HA) solution

RV-P1501-6: Gel-like product with 1 million BMMNCs in each ml of 1% hyaluronan (HA) solution
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Ankle Brachial Index (ABI)
timeFrame: Day 0, Week 4, Week 12, Week 24
Secondary outcomes:
measure: Clinical status (Rutherford category)
timeFrame: Day 0, Week 1, Week 2, Week 4, Week 12, Week 24
measure: Level of pain at rest
timeFrame: Day 0, Week 1, Week 2, Week 4, Week 12, Week 24
measure: Ulcer size in cm2
timeFrame: Day 0, Week 1, Week 2, Week 4, Week 12, Week 24
measure: Ulcer category
timeFrame: Day 0, Week 1, Week 2, Week 4, Week 12, Week 24
measure: PWT/PFWT in seconds
timeFrame: Day 0, Week 4, Week 12, Week 24
measure: Amputation free
timeFrame: Week 1, Week 2, Week 4, Week 12, Week 24
measure: Ejection fraction
timeFrame: Week 12, Week 24
measure: CT angiography
timeFrame: Week 12, Week 24
measure: Biochemistry
timeFrame: Week 12, Week 24
measure: Hematology
timeFrame: Week 12, Week 24
Other outcomes:
Locations:
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
References: