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

Primary Purpose

Critical Limb Ischemia

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cord blood stem cell injection
Sponsored by
Richard Burt, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Critical Limb Ischemia focused on measuring Cord blood injection in peripheral vascular disease

Eligibility Criteria

18 Years - 72 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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%

Sites / Locations

  • Northwestern University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

UBC injection into one leg of PVD pt

Arm Description

25 participants with severe peripheral vascular disease in leg(s) and they do not qualify for surgical treatment.

Outcomes

Primary Outcome Measures

Ankle brachial index (ABI), a 15% increase will be considered improvement
Healing of ischemic ulcers
Decreased pain level as reported by the patient

Secondary Outcome Measures

SF-36 quality of life (QOL)
Walking Impairment Questionnaire
Increase in pain free ambulation time on treadmill by more than 25%
Increase in four meter walk or six minute walk by more than 25%

Full Information

First Posted
November 19, 2009
Last Updated
January 31, 2014
Sponsor
Richard Burt, MD
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1. Study Identification

Unique Protocol Identification Number
NCT01019681
Brief Title
Efficacy and Safety of Umbilical Cord Blood Injection for Critical Limb Ischemia
Official Title
Umbilical Cord Blood Stem Cell Injection for Critical Limb Ischemia
Study Type
Interventional

2. Study Status

Record Verification Date
January 2014
Overall Recruitment Status
Terminated
Why Stopped
Only patient enrolled on study died -the cause of death not study related
Study Start Date
November 2009 (undefined)
Primary Completion Date
January 2014 (Actual)
Study Completion Date
January 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Richard Burt, MD

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Critical Limb Ischemia
Keywords
Cord blood injection in peripheral vascular disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
UBC injection into one leg of PVD pt
Arm Type
Experimental
Arm Description
25 participants with severe peripheral vascular disease in leg(s) and they do not qualify for surgical treatment.
Intervention Type
Biological
Intervention Name(s)
Cord blood stem cell injection
Other Intervention Name(s)
HSCT
Intervention Description
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).
Primary Outcome Measure Information:
Title
Ankle brachial index (ABI), a 15% increase will be considered improvement
Time Frame
Pre-transplant, 1, 6, 12 and 24 months after
Title
Healing of ischemic ulcers
Time Frame
Pre-transplant, 1, 6, 12 and 24 months after
Title
Decreased pain level as reported by the patient
Time Frame
Pre-transplant, 1, 6, 12 and 24 months after
Secondary Outcome Measure Information:
Title
SF-36 quality of life (QOL)
Time Frame
Pre-transplant, 1, 6 , 12, and 24 months after HSC transplant
Title
Walking Impairment Questionnaire
Time Frame
Pre-transplant, 1, 6 , 12, and 24 months after HSC transplant
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
72 Years
Accepts Healthy Volunteers
No
Eligibility 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 Ankle brachial index (ABI) ≤ 0.7 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%
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Burt, MD
Organizational Affiliation
Northwestern University and Northwestern Memorial Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States

12. IPD Sharing Statement

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

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