Critical Limb IschemiaPhase 1NCT01019681
Efficacy and Safety of Umbilical Cord Blood Injection for Critical Limb Ischemia
A Phase 1 study testing Cord blood stem cell injection in people with Critical Limb Ischemia, run by Richard Burt, MD at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 72 years
- Conditions the study is for
- Critical Limb Ischemia
- What is being tested?
- Cord blood stem cell injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2009to Jan 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 72 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 21Show fewer
- 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%
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Umbilical Cord Blood Stem Cell Injection for Critical Limb Ischemia
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.
Read the 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.
- Conditions
- Critical Limb Ischemia
- Being tested
- Cord blood stem cell injection
- Keywords
- Cord blood injection in peripheral vascular disease
- Medical subject headings
- Chronic Limb-Threatening Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cord blood stem cell injectionBiological
Also called HSCT
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).
| Study group | Role | What they receive |
|---|---|---|
| UBC injection into one leg of PVD pt | Experimental | 25 participants with severe peripheral vascular disease in leg(s) and they do not qualify for surgical treatment. Receives: Biological: Cord blood stem cell injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ankle brachial index (ABI), a 15% increase will be considered improvement
Measured: Pre-transplant, 1, 6, 12 and 24 months after
Healing of ischemic ulcers
Measured: Pre-transplant, 1, 6, 12 and 24 months after
Decreased pain level as reported by the patient
Measured: Pre-transplant, 1, 6, 12 and 24 months after
Secondary outcomes (4)
SF-36 quality of life (QOL)
Measured: Pre-transplant, 1, 6 , 12, and 24 months after HSC transplant
Walking Impairment Questionnaire
Measured: Pre-transplant, 1, 6 , 12, and 24 months after HSC transplant
Increase in pain free ambulation time on treadmill by more than 25%
Measured: Pre-transplant, 1, 6 , 12, and 24 months after HSC transplant
Increase in four meter walk or six minute walk by more than 25%
Measured: Pre-transplant, 1, 6 , 12, and 24 months after HSC transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2009 (estimated)
- Study startNov 2009
- Primary completionJan 2014
- Study completionJan 2014
Why it stopped: Only patient enrolled on study died -the cause of death not study related
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Critical Limb IschemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Richard Burt, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Richard Burt, MD, Northwestern University
- Investigators
- Richard Burt, MD, Principal investigator, Northwestern University and Northwestern Memorial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01019681
- Sponsor's protocol ID
- PVD.Cord.Blood.2008
- Status last verified
- Jan 2014
- First submitted
- 19 Nov 2009
- Last updated
- 3 Feb 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Umbilical Cord Blood Stem Cell Injection for Critical Limb Ischemia
- ClinicalTrials.gov ID
- NCT01019681
- Acronym / sponsor ID
- PVD.Cord.Blood.2008
- Conditions
- Critical Limb Ischemia
- Keywords
- Cord blood injection in peripheral vascular disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Only patient enrolled on study died -the cause of death not study related
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Richard Burt, MDUniversity, hospital or other
- Study start
- Nov 2009
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 25 Nov 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| UBC injection into one leg of PVD pt | Experimental | Biological: Cord blood stem cell injection25 participants with severe peripheral vascular disease in leg(s) and they do not qualify for surgical treatment. |
Who may qualify
- Ages
- 18 to 72 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Atherosclerotic ischemic peripheral vascular disease or Thromboangiitis Obliterans with Critical Limb Ischemia (Fontaine stages III and IV)
- Participant must match either a or b
- 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.
Key exclusion criteria (21 listed)
- Popliteal vascular entrapment syndrome
- Lower extremity infection or infected ulcer
- Hypercoagulable state
- HIV positive
- HBsAg positive
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cord blood stem cell injectionAlso: HSCTThe 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). | Biological | UBC injection into one leg of PVD pt |
Primary outcome
Ankle brachial index (ABI), a 15% increase will be considered improvement
Time frame: Pre-transplant, 1, 6, 12 and 24 months after
Healing of ischemic ulcers
Time frame: Pre-transplant, 1, 6, 12 and 24 months after
Decreased pain level as reported by the patient
Time frame: Pre-transplant, 1, 6, 12 and 24 months after
4 secondary outcomes
SF-36 quality of life (QOL)
Time frame: Pre-transplant, 1, 6 , 12, and 24 months after HSC transplant
Walking Impairment Questionnaire
Time frame: Pre-transplant, 1, 6 , 12, and 24 months after HSC transplant
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
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
Results and safety
The study was stopped early (reason given: Only patient enrolled on study died -the cause of death not study related). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard Burt, MD principal investigator
Northwestern University and Northwestern Memorial Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cord blood stem cell injection in people with Critical Limb Ischemia, run by Richard Burt, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Only patient enrolled on study died -the cause of death not study related). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ankle brachial index (ABI), a 15% increase will be considered improvement (time frame: Pre-transplant, 1, 6, 12 and 24 months after). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2014.