Efficacy and Safety of Umbilical Cord Blood Injection for Critical Limb Ischemia

This study has been terminated.
(Only patient enrolled on study died -the cause of death not study related)
Sponsor:
Information provided by (Responsible Party):
Richard Burt, MD, Northwestern University
ClinicalTrials.gov Identifier:
NCT01019681
First received: November 19, 2009
Last updated: January 31, 2014
Last verified: January 2014
  Purpose

The purpose of this study is to determine whether treatment with umbilical cord blood stem cells will improve blood flow to the most severely affected leg of a participant with medically refractory and non-surgical peripheral vascular disease of the lower extremity.


Condition Intervention Phase
Critical Limb Ischemia
Biological: Cord blood stem cell injection
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Umbilical Cord Blood Stem Cell Injection for Critical Limb Ischemia

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Ankle brachial index (ABI), a 15% increase will be considered improvement [ Time Frame: Pre-transplant, 1, 6, 12 and 24 months after ] [ Designated as safety issue: Yes ]
  • Healing of ischemic ulcers [ Time Frame: Pre-transplant, 1, 6, 12 and 24 months after ] [ Designated as safety issue: Yes ]
  • Decreased pain level as reported by the patient [ Time Frame: Pre-transplant, 1, 6, 12 and 24 months after ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • SF-36 quality of life (QOL) [ Time Frame: Pre-transplant, 1, 6 , 12, and 24 months after HSC transplant ] [ Designated as safety issue: Yes ]
  • Walking Impairment Questionnaire [ Time Frame: Pre-transplant, 1, 6 , 12, and 24 months after HSC transplant ] [ Designated as safety issue: Yes ]
  • Increase in pain free ambulation time on treadmill by more than 25% [ Time Frame: Pre-transplant, 1, 6 , 12, and 24 months after HSC transplant ] [ Designated as safety issue: Yes ]
  • Increase in four meter walk or six minute walk by more than 25% [ Time Frame: Pre-transplant, 1, 6 , 12, and 24 months after HSC transplant ] [ Designated as safety issue: Yes ]

Enrollment: 1
Study Start Date: November 2009
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: UBC injection into one leg of PVD pt
25 participants with severe peripheral vascular disease in leg(s) and they do not qualify for surgical treatment.
Biological: Cord blood stem cell injection

The cord blood stem cells will be simply injected intramuscularly in the leg. 30 minutes prior to stem cell injection the patients will receive Vancomycin 1 gram IVPB x1 as a prophylactic measure. Patients will also receive Ativan 0.5 to 1 mg PO x 1 and Dilaudid 0.5 to 1 mg IV x1 to alleviate the discomfort of the procedure.

Cells will be injected by means of a 22 gauge sterile spinal needle after topical anesthesia of the injection site. The concentration will be at least 2 x 107 total nucleated cells per ml in phosphate buffered saline (PBS) with 5% human serum albumin (Baxter, Deerfield Illinois).

Other Name: HSCT

Detailed Description:

Umbilical cord blood is a safe alternative source of stem cells used for decades in hematopoietic stem cell transplants for malignancies. There is also a reported decreased incidence of acute GVHD compared to matched unrelated donor transplants.A cord blood registry will be searched for suitable units with compatibility in the ABO and HLA systems. The minimum total nucleated cell dose required which would be 1.0 x 107/kg, and one unit of cells will be procured to meet this requirement. Although it is likely that the transplanted cord blood cells will be rejected over time, we hypothesize that while they remain in the host's tissue these cells will be producing and releasing cytokines, growth factors and other humoral factors that might promote vasculogenesis by stimulating endogenous stem cells and endothelial cells. Since there is no need to collect the patient's own stem cells, the patient's cardiovascular system will not be subjected to any stress due to the leukapheresis procedure itself. No injections of exogenous growth factors, which have been associated with thrombosis, would be required to mobilize the patient's own stem cells. The procedure could conceivably even be performed in its entirety on an outpatient basis.

A total of 25 patients will be enrolled in the study. Patients will be followed for 24 months after the procedure with evaluation visits one day after the transplant and then at one month, six, twelve and twenty four months post-treatment. The visit one day after the transplant will involve a history and physical with a leg exam, a CBC and a chemistry panel to evaluate for possible infection, or other adverse event.

  Eligibility

Ages Eligible for Study:   18 Years to 72 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Atherosclerotic ischemic peripheral vascular disease or Thromboangiitis Obliterans with Critical Limb Ischemia (Fontaine stages III and IV)
  • Participant must match either a or b

    1. Ankle brachial index (ABI) ≤ 0.7
    2. Doppler waveforms at posterior tibial artery and dorsalis pedis artery are monophasic with toe pressure < 30 mmHg.
  • 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.
  • Age > 18 years old.
  • The non-index leg may be treated only in the event and it full fills the same eligibility criteria and exclusion criteria used in this protocol for the treatment leg.
  • Patients must be on maximal tolerated medical therapy for PVD including A) Cessation of smoking B) Referral to endocrinologist for control of HgA1c to < 7.0 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)

Exclusion Criteria:

  • Popliteal vascular entrapment syndrome
  • Lower extremity infection or infected ulcer
  • Hypercoagulable state
  • HIV positive
  • HBsAg positive
  • Uncontrolled arrhythmia, that is, persistence of an arrhythmia despite medical therapy
  • Unstable angina
  • Thrombocytopenia < 50,000/ul
  • Leukemia or myelodysplasia
  • Allergy to E coli or its products
  • Patients with metal in their bodies cannot undergo MRIs (MRA). Therefore, patients with, cochlear implants, or aneurysm clips are not eligible. Coronary artery stents are not a contraindication. Patients with pacemakers are still candidates provided they have normal creatinine (< 1.1 mg/dl) and can receive contrast dye (no allergy) for angiogram instead of MRA. MRI/MRA does not need to be repeated if a prior MRA or Angiogram Demonstrates inoperable disease.
  • Patients who are pregnant
  • Poorly controlled diabetes will not be a cause for exclusion but patient must see endocrinologist for better control
  • Current malignancy, except squamous cell or basal cell skin cancers thought to be easily controlled.
  • AST, ALT, or bilirubin more than twice the upper limit of normal.
  • WBC < 2.5 / ul.
  • Any patient who is actively bleeding, including blood on urine dipstick or fecal occult blood.
  • Patient is on chemotherapy or other immuno-suppressive medications such as steroids, cellcept, cyclosporine, cytoxan, azathioprine, rituxan, humira or remicade.
  • Donor is HLA homozygous and shares that HLA haplotype with the recipient (a different donor will have to be found)
  • Patients diagnosed with Thromboangiitis Obliterans (Buerger's Disease) who are smokers and are unwilling or unable to quit smoking
  • A) Patients with a myocardial infarction within the last 30 days or left ventricular ejection fraction < 35% B) Patients with a history of malignancy in the last 5 years (other than basal cell carcinoma or carcinoma in situ) C) Patients with a CVA within the last 6 months D) Patients with a HbA1c level > 7.0%
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01019681

Locations
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Richard Burt, MD
Investigators
Principal Investigator: Richard Burt, MD Northwestern University and Northwestern Memorial Hospital
  More Information

No publications provided

Responsible Party: Richard Burt, MD, MD, Northwestern University
ClinicalTrials.gov Identifier: NCT01019681     History of Changes
Other Study ID Numbers: PVD.Cord.Blood.2008
Study First Received: November 19, 2009
Last Updated: January 31, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Northwestern University:
Cord blood injection in peripheral vascular disease

Additional relevant MeSH terms:
Ischemia
Pathologic Processes

ClinicalTrials.gov processed this record on April 14, 2014