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

NCT01472289 | Completed Phase 1 Results DMC

• 2 other identifiers: TPSC/POC/BMSC/CLI/2010/1b050343290-0702201132855389
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Critical Limb Ischemia

Keywords

CLI; Peripheral arterial disease

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events as a Measure of Safety and Major Limb Amputation Free Survival Post BMMNC Administration

  The Primary objective of this study was to determine the safety of intramuscular administration of concentrated autologous BMMNCs harvested, and processed using the Res-Q 60 technology (a point-of-care system). Safety measurements included close vigilance for major limb amputation free survival at 1, 3, 6 and 12 months post BMMNCs administration and stringent reporting of AEs and SAEs.

  1, 3, 6 and 12 Months

Secondary Outcomes (6)

• Degree of Angiogenesis Measured by the Number of Collateral Blood Vessels Formed at 12 Months

  Baseline and 12 month

• Measurement of Mean Change in Ankle Brachial Index From Baseline to 12 Months

  Baseline, 1, 3, 6 and 12 months

• Measurement of Change in Transcutaneous Oxygen Pressure (TcPO2) From Baseline to 12 Months

  Baseline, 1, 3, 6 and 12 months

• Change in Rest Pain and Intermittent Claudication Assessment From Baseline to 12 Months

  Baseline, 1, 3, 6 and 12 months

• Clinical Evaluation for the Presence of Ulcer and/or Gangrene in the Affected Limb From Baseline to 12 Months

  Baseline, 1, 3, 6 and 12 months

Study Arms (1)

BMMNC treated group

EXPERIMENTAL

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.

Other: Autologous Bone Marrow Mononuclear cells (BMMNCs)

Interventions

Autologous Bone Marrow Mononuclear cells (BMMNCs) OTHER

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

Also known as: Autologous bone marrow mononuclear cell concentrate

BMMNC treated group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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%.

Sponsors & Collaborators

• TotipotentSC Scientific Product Pvt. Ltd.: lead
• Thermogenesis Corp.: collaborator

Study Sites (1)

Fortis Escorts Heart Institute & Research Centre

New Delhi, New Delhi, India

Location

MeSH Terms

Conditions

Chronic Limb-Threatening Ischemia; Peripheral Arterial Disease

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ischemia

Results Point of Contact

• Title: Dr. Venkatesh Ponemone
• Organization: TotipotentSC

venkatesh.ponemone@totipotentsc.com

+91-124-4976860

Study Officials

• Venkatesh Ponemone, PhD

  TotipotentRX, Center for Cellular Medicine

  STUDY DIRECTOR

• Kenneth Harris, MS

  TotipotentRX, Centre for Cellular Medicine

  STUDY CHAIR

• Suhail Bukhari, MBBS, FNBE

  Fortis Escorts Heart Institute and Research Centre

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2011
• First Posted: November 16, 2011
• Study Start: February 1, 2011
• Primary Completion: January 1, 2013
• Study Completion: July 1, 2013
• Last Updated: November 18, 2015
• Results First Posted: November 18, 2015

Record last verified: 2015-10

Locations

IN (1)