Safety and Efficacy of Autologous Bone Marrow Mononuclear Cells in Patients With Severe Critical Limb Ischemia

NCT ID: NCT01472289

Last Updated: 2015-11-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-28
• Study Completion Date: 2013-07-31

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of the concentrated autologous bone marrow derived stem cells for the treatment of Critical Limb Ischemia patients.

Detailed Description

A total of 15 patients suffering from end stage IV and V Rutherford /CLI in whom all previous therapeutic strategies failed (e.g. surgical revascularization) will be selected and undergo local transplantation of autologous BMMNCs. Conventional treatments include angioplasty and /or bypass to remove blood vessel blockage for restoring blood supply, along with prescribed medicines that aid in ulcer recovery and wound healing and debridement of damaged/infected tissue. Amputation is inevitable in many cases because some blood capillaries cannot be corrected and restenosis of vessels is very common. Cell therapies with mononuclear cells from patients own bone marrow is promising because these stem cells are capable of stimulating and regenerating capillaries and blood vessels (neovascularization).

This is a Phase Ib (feasibility study), prospective, non randomized and open labeled study aimed to find out the safety and efficacy of intramuscular autologous bone marrow mononuclear cells implantation in patients with chronic critical limb ischemia.

The efficacy/safety of this therapy will be assessed by using several endpoints such as (a) prevention of amputation, (b) wound healing and (c) degree of angiogenesis. In order to assess the limb ischemia, the measurements will be performed at pre- and post transplantation at a variety of time intervals. The measurements include: ABI-ankle brachial index, Transcutaneous partial pressure of Oxygen (TcPO2), 6 min walk test, Rest pain and intermittent Claudication assessment, Healing of ulcers/ wounds and angiography of the affected limb.

Conditions

Critical Limb Ischemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BMMNC treated group

Autologous bone marrow mononuclear cell concentrate (BMMNCs) prepared using the Res-Q 60 technology (a point of care system) to be injected intramuscularly into multiple sites in the ischemic muscle tissue of the affected limb at 0.5 cc/injection for a total of 15-20 cc.

Group Type: EXPERIMENTAL

Autologous Bone Marrow Mononuclear cells (BMMNCs)

Intervention Type: OTHER

Multiple intramuscular injections of concentrated bone marrow derived mononuclear cells (0.5 cc/injection) into the ischemic muscle of the affected limb.

Interventions

Autologous Bone Marrow Mononuclear cells (BMMNCs)

Multiple intramuscular injections of concentrated bone marrow derived mononuclear cells (0.5 cc/injection) into the ischemic muscle of the affected limb.

Intervention Type: OTHER

Other Intervention Names

Autologous bone marrow mononuclear cell concentrate

Eligibility Criteria

Inclusion Criteria

• Atherosclerotic ischemic peripheral vascular disease (PVD) or Thromboangiitis Obliterans with severe Critical Limb Ischemia (Rutherford Category 4 and 5: ischemic pain at rest and minor tissue loss and Fontaine Class 4: Ischemic ulcers or gangrene, whivh may be dry or humid).
• A non-surgical candidate for revascularization e.g. prior vascular reconstruction, inability to locate a suitable vein for grafting, diffuse multi- segment disease, or extensive infra-popliteal disease not amenable to a vascular graft.
• Major amputation recommended patients due to severe life threatening PAD.
• Subjects must be on maximal tolerated medical therapy for peripheral vascular disease including A) Cessation of smoking B) Referral to endocrinologist for control of HgA1c to < 8% mg/dl, C) control of hyperlipidemia with statins or other anti-hyperlipidemic drugs as indicated, D) control of hypertension as indicated E) Antiplatelet therapy with aspirin and / or cilostazol (unless medically contraindicated, e.g. bleeding or allergy).
• Ankle Brachial Pressure Index (ABI) ≤ 0.6 or ankle systolic pressure ≤ 60 mm Hg or TcPO2 ≤ 35 mmHg in the foot.
• Subjects who are able to understand the requirements of the study, and willing to provide voluntary written informed consent, which abide by the study requirements, and agree to return for required follow-up visits.

Exclusion Criteria

• Subjects with CLI suitable for surgical or percutaneous revascularization and Subjects with acute and chronic inflammatory condition.
• CLI patient requiring amputation proximal to trans-metatarsal level
• Subjects with spreading (wet) gangrene
• Subjects with gait disturbance for reasons other than CLI.
• Subjects with poorly controlled diabetes mellitus.
• Subjects diagnosed with Thromboangiitis Obliterans (Buerger's Disease) who are smokers and are unwilling or unable to quit smoking or the physician feels the smoking cessation is doubtful.
• Subjects having moderate to severe COPD with GOLD Classification IIb or III.
• Uncontrolled congestive heart failure or Subjects with left ventricular ejection fraction < 25% or AHA Stage C or D heart failure or NYHA Class IV CHF
• Stroke or myocardial infarction within last 3 months.
• Subjects who are contraindicated for CT Angiogram.
• Illnesses or conditions that are uncontrolled or whose control, in the opinion of the Principal Investigator, may be jeopardized by participation in this study or by the complications of this therapy.
• Documented terminal illness or cancer or any concomitant disease process with a life expectancy of less than 1 year.
• Subjects already enrolled in another investigational drug trial or completed within 3 months.
• History of severe alcohol or drug abuse within 3 months of screening.
• Hb% < 10 gm%; Serum creatinine ≥ 2.0mg%; Serum total bilirubin ≥2.0mg%; HbA1c > 8.0%.
• Women of child bearing potential; pregnant and lactating women.
• Subjects with a) myocardial infarction within the last 30 days or left ventricular ejection fraction < 35%, B) Subjects with a cerebrovascular accident within the last 6 months.
• INR > 1.5 at the time of Bone Marrow harvest.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Thermogenesis Corp.

INDUSTRY

Sponsor Role: collaborator

TotipotentSC Scientific Product Pvt. Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Venkatesh Ponemone, PhD

Role: STUDY_DIRECTOR

TotipotentRX, Center for Cellular Medicine

Kenneth Harris, MS

Role: STUDY_CHAIR

TotipotentRX, Centre for Cellular Medicine

Suhail Bukhari, MBBS, FNBE

Role: PRINCIPAL_INVESTIGATOR

Fortis Escorts Heart Institute and Research Centre

Locations

Fortis Escorts Heart Institute & Research Centre

New Delhi, New Delhi, India

Countries

India

Other Identifiers

050343290-0702201132855389

Identifier Type: REGISTRY

Identifier Source: secondary_id

TPSC/POC/BMSC/CLI/2010/1b

Identifier Type: -

Identifier Source: org_study_id