Umbilical Cord Blood Stem Cell Injection for Critical Limb Ischemia
Efficacy and Safety of Umbilical Cord Blood Injection for Critical Limb Ischemia
Sponsors
Source
Northwestern University
Oversight Info
Has Dmc
No
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.
Overall Status
Terminated
Start Date
2009-11-01
Completion Date
2014-01-01
Primary Completion Date
2014-01-01
Phase
Phase 1
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
|
Ankle brachial index (ABI), a 15% increase will be considered improvement |
Pre-transplant, 1, 6, 12 and 24 months after |
|
Healing of ischemic ulcers |
Pre-transplant, 1, 6, 12 and 24 months after |
|
Decreased pain level as reported by the patient |
Pre-transplant, 1, 6, 12 and 24 months after |
Secondary Outcome
Measure |
Time Frame |
|
SF-36 quality of life (QOL) |
Pre-transplant, 1, 6 , 12, and 24 months after HSC transplant |
|
Walking Impairment Questionnaire |
Pre-transplant, 1, 6 , 12, and 24 months after HSC transplant |
|
Increase in pain free ambulation time on treadmill by more than 25% |
Pre-transplant, 1, 6 , 12, and 24 months after HSC transplant |
|
Increase in four meter walk or six minute walk by more than 25% |
Pre-transplant, 1, 6 , 12, and 24 months after HSC transplant |
Enrollment
1
Condition
Intervention
Intervention Type
Biological
Intervention Name
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).
Arm Group Label
UBC injection into one leg of PVD pt
Other Name
HSCT
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
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%
Gender
All
Minimum Age
18 Years
Maximum Age
72 Years
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
|
Richard Burt, MD |
Principal Investigator |
Northwestern University and Northwestern Memorial Hospital |
Location
Facility |
|
Northwestern University Chicago Illinois 60611 United States |
Location Countries
Country
United States
Verification Date
2014-01-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor-Investigator
Investigator Affiliation
Northwestern University
Investigator Full Name
Richard Burt, MD
Investigator Title
MD
Keyword
Has Expanded Access
No
Condition Browse
Number Of Arms
1
Arm Group
Arm Group Label
UBC injection into one leg of PVD pt
Arm Group Type
Experimental
Description
25 participants with severe peripheral vascular disease in leg(s) and they do not qualify for surgical treatment.
Firstreceived Results Date
N/A
Why Stopped
Only patient enrolled on study died -the cause of death not study related
Firstreceived Results Disposition Date
N/A
Study Design Info
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)
Study First Submitted
November 19, 2009
Study First Submitted Qc
November 24, 2009
Study First Posted
November 25, 2009
Last Update Submitted
January 31, 2014
Last Update Submitted Qc
January 31, 2014
Last Update Posted
February 3, 2014
ClinicalTrials.gov processed this data on December 05, 2019
Conditions
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conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.