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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Thermogenesis Corp.
Information provided by (Responsible Party):
TotipotentSC Scientific Product Pvt. Ltd.
ClinicalTrials.gov Identifier:
NCT01472289
First received: July 18, 2011
Last updated: September 2, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Critical Limb Ischemia
Other: Autologous Bone Marrow Mononuclear cells
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: To Study and Demonstrate the Safety and Efficacy of RES-Q Prepared Bone Marrow Mononuclear Cells Injected Into Ischemic Tissue of Patients With Non-Reconstructable Critical Limb Ischemia (CLI).

Further study details as provided by TotipotentSC Scientific Product Pvt. Ltd.:

Primary Outcome Measures:
  • Number of adverse events as a measure of Safety and limb salvage [ Time Frame: 12 Months ] [ Designated as safety issue: Yes ]
    The measure is the number of adverse events and major limb amputations within 12 months from the procedure.


Secondary Outcome Measures:
  • Disease severity [ Time Frame: 12 month ] [ Designated as safety issue: No ]
    Measurement of clinical endpoints such as Ankle brachial index (ABI), Transcutaneous Partial Pressure of Oxygen (TcPO2) and measurement of blood supply by CT angiography after the procedure.

  • Change in Rest Pain [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Ulcer Healing [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Assessment of Co-morbidity [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 15
Study Start Date: February 2011
Estimated Study Completion Date: November 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BMMNC treated group
Autologous bone marrow concentrate prepared using Res-Q60 (a point of care system) to be injected intramuscularly into multiple sites of the ischemic muscle tissue of the affected limb at 0.5 cc/injection for a total of 15-20 cc.
Other: Autologous Bone Marrow Mononuclear cells
Multiple intramuscular injections of concentrated bone marrow derived mononuclear cells (0.5 cc/injection) into the ischemic muscle of the affected limb.
Other Name: Autologous bone marrow concentrate

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 I/II, prospective, non randomized and open labeled study aimed to find out the safety and efficacy of intramuscular autologous bone marrow mononuclear cells implantation only 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, Healing of ulcers/ wounds and angiography of the affected limb.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Atherosclerotic ischemic peripheral vascular disease or Thromboangiitis Obliterans with severe Critical Limb Ischemia (Rutherford Category 4 and 5: ischemic pain at rest and minor tissue loss).
  • 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, control of hyperlipidemia with statins or other anti-hyperlipidemic drugs as indicated, control of hypertension as indicated C) 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, 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01472289

Locations
India
Fortis Escorts Heart Institute & Research Centre
New Delhi, India
Sponsors and Collaborators
TotipotentSC Scientific Product Pvt. Ltd.
Thermogenesis Corp.
Investigators
Study Director: Venkatesh Ponemone, PhD TotipotentRX, Center for Cellular Medicine
Study Chair: Kenneth Harris, MS TotipotentRX, Centre for Cellular Medicine
Principal Investigator: Suhail Bukhari, MBBS, FNBE Fortis Escorts Heart Institute and Research Centre
  More Information

No publications provided

Responsible Party: TotipotentSC Scientific Product Pvt. Ltd.
ClinicalTrials.gov Identifier: NCT01472289     History of Changes
Other Study ID Numbers: TPSC/POC/BMSC/CLI/1.1, 050343290-0702201132855389
Study First Received: July 18, 2011
Last Updated: September 2, 2013
Health Authority: India: Indian Council of Medical Research

Keywords provided by TotipotentSC Scientific Product Pvt. Ltd.:
CLI
Peripheral arterial disease

Additional relevant MeSH terms:
Ischemia
Pathologic Processes

ClinicalTrials.gov processed this record on July 26, 2014