Feasability Study of Autologous Bone Marrow Aspirate Concentrate for Treatment of CLI

Feasibility Study of the Safety and Activity of Autologous Bone Marrow Aspirate Concentrate (BMAC) for the Treatment of Non Reconstructable Critical Limb Ischemia Due to Peripheral Arterial Occlusive Disease

The purpose of this study is to determine if concentrated nucleated cells from your own bone marrow, injected or infused into an ischemic limb, will restore sufficient blood flow to avoid amputation.

Study Overview

• Status: Completed
• Conditions: Arterial Occlusive Diseases
• Intervention / Treatment: Device: centrifuge, laboratory, tabletop (SmartPReP2 BMAC System)

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• India
  • Chennai
    • Porur, Chennai, India, 600 116
      • Sri Ramachandra University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of Critical Limb Ischemia per protocol (see diagnostic criteria #2) with regard to the study limb.

   Existence of a PAOD with clinical presentation corresponding to Rutherford Category 4 or Category 5 as defined in the reporting standards adopted by the Society of Vascular Surgeons (table 1)

2. Patient meets at least one of the following diagnostic criteria in the study limb:

   • Ankle artery occlusion pressure absolute <50 mmHg or ABI <0.4
   • Toe artery occlusive pressure < 40mm Hg or TBI (<0.4)
   • TcPO2 <20 mmHg lying down breathing room air, if available.

3. There is no reasonable open surgical or endovascular revascularization option as determined by the treating vascular specialist. Factors that may contribute to the determination of inoperability may include:

   • Anatomical considerations

     • No outflow targets
     • No appropriate conduit (i.e. vein for bypass)
     • Long segment occlusions or calcified lesions that predict poor outcome with endovascular approaches.

   • High risk medical conditions

     • Unstable cardiac disease.
     • Renal insufficiency
   • History of prior failed revascularization attempts

   • The patient's unsuitability must be confirmed by 2 qualified physicians.

     • The attending vascular surgeon will provide the primary assessment.
     • The confirmatory opinion must come from a fully licensed physician. (not a resident)
     • If anatomical considerations are invoked, the second physician may be a vascular surgeon, interventional radiologist, cardiologist, or vascular medicine specialist.
     • If medical co-morbidity is deemed the high risk aspect, then the confirmatory opinion may be obtained from an internist, family physician, cardiologist, vascular medicine, nephrologists, or vascular surgeon.
4. Age >18 years and ability to understand the planned treatment
5. Subject has read and signed the IRB/IEC approved Informed Consent form
6. Patients for whom the following medication(s) is prescribed must have a one month stable baseline of appropriate/maximally tolerated therapy prior to enrollment: Plavix/asprin therapy, anticoagulation therapy, cholesterol lowering agent, and or blood pressure medication
7. Hematocrit ≥ 28.0%, White Blood Cell count ≤ 14,000, Platelet count ≥ 50,000, INR ≤ 1.6 unless on Coumadin, or PTT <1.5 x control (to avoid bleeding complications) Patients on Coumadin will be corrected prior to the procedure and must have an INR<1.6 at the time of randomization/surgery.

Exclusion Criteria:

1. Life expectancy <6 months due to concomitant illnesses
2. History of bone marrow diseases (especially NHL, MDS) that prohibit transplantation
3. Terminal renal failure with existing dependence on dialysis
4. Known active malignancy or results outside of normal limits from the following tests: PAP, Chest X-ray, PSA, Mammogram, Hemocult unless follow-up studies reveal patient to be cancer free..
5. Poorly controlled diabetes mellitus (HgbA1C>10%)
6. Medical risk that precludes anesthesia (conscious sedation), or ASA Class 5
7. Life-threatening complications of the ischemia necessitating immediate amputation
8. Uncorrected iliac artery occlusion on index side
9. Extensive necrosis of the index limb or other conditions that make amputation inevitable (Rutherford Category 6)
10. Active clinical infection being treated by antibiotics within one week of enrollment
11. Treatment with immunosuppressant drugs (including Prednisone > 5 mg per day).
12. Female who is pregnant or nursing, or of child bearing potential and is not using a reliable birth control method.
13. Underwent a major cardiovascular surgical procedure (carotid endarterectomy, open arterial aneurysm or bypass surgery, or coronary artery bypass surgery) or an adverse cardiovascular event (stroke or MI) within the 30 days prior to randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; injection of BMAC into ischemic limb	Device: centrifuge, laboratory, tabletop (SmartPReP2 BMAC System); autologous bone marrow aspirate will be concentrated using the SmartPRep2 BMAC system and then injected/infused into ischemic limbs; Other Names: SmartPReP2 BMAC System
Active Comparator: 2; Injection and Infusion of BMAC into ischemic lower limb	Device: centrifuge, laboratory, tabletop (SmartPReP2 BMAC System); autologous bone marrow aspirate will be concentrated using the SmartPRep2 BMAC system and then injected/infused into ischemic limbs; Other Names: SmartPReP2 BMAC System

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
avoid amputation	60 days

Secondary Outcome Measures

Outcome Measure	Time Frame
measurement of hemodynamic response	60 Days

Collaborators and Investigators

• Sponsor: Harvest Technologies
• Investigators: Study Director: R E Arasan, MD, LifeCell India

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: December 19, 2007
• First Submitted That Met QC Criteria: January 15, 2008
• First Posted (Estimate): January 16, 2008

Study Record Updates

• Last Update Posted (Estimate): March 9, 2012
• Last Update Submitted That Met QC Criteria: March 8, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: PAD, CLI, Critical Limb Ischemia, bone marrow, stem cell, injection, infusion
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arterial Occlusive Diseases
• Other Study ID Numbers: TriCell/CT/IND-001