Critical Limb IschemiaPhase 1/2CLI-001NCT00392509
ALD-301 for Critical Limb Ischemia, Randomized Trial
A Phase 1/2 study testing ALDH-br bone marrow cells vs. mononuclear bone marrow cells in people with Critical Limb Ischemia and Peripheral Arterial Disease, run by Aldagen at 5 sites in United States.
Trial summary
This study will treat patients with such severe lower leg ischemia or vascular compromise that they have pain at rest. The goal is to compare treatment of the patient's painful disorder by injecting cells into the calf of the leg and testing for circulatory improvement. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Critical Limb Ischemia, Peripheral Arterial Disease, Peripheral Vascular Disease
- What is being tested?
- ALDH-br bone marrow cells vs. mononuclear bone marrow cells
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 5 sitesUnited States
- Study dates
- Oct 2006to Dec 2008
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients 18 years of age or greater with atherosclerotic vascular disease that is viewed as not readily amenable to reconstructive surgery and Rutherford Category 4 ischemia (ischemic rest pain) and Rutherford Category 5 ischemia (ulceration or tissue necrosis) and by the judgment of their referring physician are not reasonable candidates for revascularization options of either percutaneous balloon angioplasty or a surgical revascularization.
- Objective evidence of severe peripheral arterial disease will include an ankle brachial index (ABI) of less than 0.5, or, in the case of patients who have vessels calcified and thereby "non-compressible" vessels metatarsal pulse volume recording (PVR) that is flat or barely pulsatile in the diseased limb on two consecutive examinations performed at least one week apart.
- Patients competent to give informed consent.
- No active malignant disease that could involve the bone marrow, or history of treatment of malignant disease that could have damaged the bone marrow.
- Before being accepted for the study the patient must be screened for human immunodeficiency virus, hepatitis B virus, hepatitis C virus, human transmissible spongiform encephalopathy, including Creutzfeldt-Jacob Disease, Treponema pallidum, and have a negative standard infectious disease panel including a CMV PCR test.
- Patients who are hemodynamically stable.
Who cannot join
- Patients with poorly controlled diabetes mellitus (HbA1C > 8%)
- Patients with renal insufficiency (creatinine > 2.5).
- Patients with evidence of infectious disease as determined by e. above or other medical findings.
- Pregnant women (women capable of childbearing must have a negative pregnancy test).
- Patients with cognitive impairments.
- Other comorbid disease that would be expected to result in less than one year life expectancy
Show all 17Show fewer
- Past malignancy or history of chemotherapy or radiation affecting the bone marrow.
- History of inflammatory or progressively fibrotic conditions: .e.g., rheumatoid arthritis, systemic lupus erythematosis, vasculitic disorders, idiopathic pulmonary fibrosis, retroperitoneal fibrosis
- Infection as evidenced by WBC count of >15,000 and/or temperature >38 degrees C. Large area of cellulitis in the afflicted limb that in the opinion of the investigators would require the institution of antibiotics OR evidence of osteomyelitis corroborated by radiographic or scintigraphic examination
- Cardiovascular conditions:
- Exercise limiting angina ( Canadian Cardiovascular Society Class 3 (Appendix 7);
- Congestive heart failure (New York Heart Association class 3 (Appendix 5);
- Unstable angina;
- Acute ST elevation myocardial infarction (MI) within 1month;
- Transient ischemic attack or stroke within 1 month;
- Severe valvular disease
- Patients with any history of organ transplants;
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Saint Joseph's Research Institute
Atlanta, Georgia, 30342
Cardiology PC
Birmingham, Alabama, 35211
Duke University Medical Center
Durham, North Carolina, 27710
Texas Heart Institute, Stem Cell Center, 6770 Bertner, St Luke's Episcopal Hospital
Houston, Texas, 77030
University of Indiana at Indianapolis
Indianapolis, Indiana, 46202
About this study
Official title: A Phase I-II Randomized Autologous Bone Marrow Derived Aldehyde Dehydrogenase-Bright (ALDHbr) Cells Against Unfractionated Autologous Mononuclear Bone Marrow in Patients With Rutherford 4 or 5 Peripheral Arterial Occlusive Disease
This study will treat patients with such severe lower leg ischemia or vascular compromise that they have pain at rest. The goal is to compare treatment of the patient's painful disorder by injecting cells into the calf of the leg and testing for circulatory improvement. A treatment will given at random to two groups and will be injection into the calf muscle with ALD-301 (specially processed stem and progenitor cells) from the patient's own bone marrow, or with cells processed by more routine that minimally purifies the cells. The study goal is to see if the ALD-301 cells are more effective in generating new small blood vessels to improve the circulation to the affected leg.
Read the detailed description
Patients will be recruited who have critical limb ischemia with pain at rest. The study will select patients for treatment and follow them for three months after intervention. The treatment will consist of drawing about 2/3 of a cup of bone marrow from the patient's hip bone, then processing the collected bone marrow will be as follows:
- The test group's bone marrow will be processed and sorted to identify the aldehyde dehydrogenase bright ALDH-br stem and progenitor cells (ALD-301). These cells will be injected into the calf muscle of the patient in clinic.
- The control group will have the same amount of bone marrow collected but it will undergo a simpler process to isolate the mononuclear cells from the whole bone marrow, removing most of the red cells and granulocytes from cell preparation for injection.
The patients will be monitored for adverse events related to this process to determine the safety of the approach. They will also be tested at intervals during the study to compare baseline values of each patient with the post-treatment values of:
- ankle-brachial index of systolic blood pressure
- the transcutaneous oxygen measurements obtained from the skin of the treated leg
- the patient's perception of his/her quality of life as measured by two different, validated questionnaires
- Measurements of of heel/foot ulcers, if present, to monitor degree of healing if it occurs
- the patient's perception of his/her level of pain in the leg
The patients will receive a call at 6 months to report on additional life events following the study.
- Being tested
- ALDH-br bone marrow cells vs. mononuclear bone marrow cells
- Keywords
- critical limb ischemia, cell therapy for angiogenesis, aldehyde dehydrogenase-bright cells, peripheral artery disease, peripheral vascular disease, leg pain, PVD, PAD, CLI, amputation, limb salvage
- Medical subject headings
- Chronic Limb-Threatening Ischemia, Peripheral Arterial Disease, Peripheral Vascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALDH-br bone marrow cells vs. mononuclear bone marrow cellsProcedure or surgery
Surgery
| Study group | Role | What they receive |
|---|---|---|
| 2 | Experimental | Unfractionated Autologous Mononuclear Bone Marrow Receives: Procedure: ALDH-br bone marrow cells vs. mononuclear bone marrow cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
adverse events
Measured: 6 months
ankle-brachial systolic pressure index
Measured: 3 mo
transcutaneous oxygen value (mm Torr)
Measured: 3 mo
quality of life (questionnaires)
Measured: 3 mo
Secondary outcomes (4)
size of lower extremity ulcer(s)
Measured: 3 mo
peripheral nerve conduction exam
Measured: 3 mo
level of pain at rest (questionnaire)
Measured: 3 mo
limb clinical status
Measured: 3 mo
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2006 (estimated)
- Study startOct 2006
- Primary completionDec 2008
- Study completionDec 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aldagen
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Emerson C Perin, M.D., Ph.D., Principal investigator, Stem Cell Center, Texas Heart Institute, St Luke's Episcopal Hospital, 6770 Bertner , Suite 1020 Texas Medical Center,Houston, Texas 77030Robert Mitchell, MD, Principal investigator, Duke UniversityMichael Murphy, MD, Principal investigator, University of Indiana at IndianapolisNicolas Chronos, MD, Principal investigator, Saint Joseph's Research InstituteFarrell Mendelsohn, MD, Principal investigator, Cardiology PC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00392509
- Sponsor's protocol ID
- BB IND 12875
- Acronym
- CLI-001
- Status last verified
- May 2009
- First submitted
- 25 Oct 2006
- Last updated
- 14 May 2009
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Perin EC, Silva G, Gahremanpour A, Canales J, Zheng Y, Cabreira-Hansen MG, Mendelsohn F, Chronos N, Haley R, Willerson JT, Annex BH. A randomized, controlled study of autologous therapy with bone marrow-derived aldehyde dehydrogenase bright cells in patients with critical limb ischemia. Catheter Cardiovasc Interv. 2011 Dec 1;78(7):1060-7. doi: 10.1002/ccd.23066. Epub 2011 May 18.
PubMed 21594960
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I-II Randomized Autologous Bone Marrow Derived Aldehyde Dehydrogenase-Bright (ALDHbr) Cells Against Unfractionated Autologous Mononuclear Bone Marrow in Patients With Rutherford 4 or 5 Peripheral Arterial Occlusive Disease
- ClinicalTrials.gov ID
- NCT00392509
- Acronym / sponsor ID
- CLI-001 / BB IND 12875
- Keywords
- critical limb ischemia, cell therapy for angiogenesis, aldehyde dehydrogenase-bright cells, peripheral artery disease, peripheral vascular disease, leg pain, PVD, PAD
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- AldagenIndustry (pharma, biotech, devices)
- Study start
- Oct 2006
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 26 Oct 2006 (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.
This study will treat patients with such severe lower leg ischemia or vascular compromise that they have pain at rest. The goal is to compare treatment of the patient's painful disorder by injecting cells into the calf of the leg and testing for circulatory improvement. A treatment will given at random to two groups and will be injection into the calf muscle with ALD-301 (specially processed stem and progenitor cells) from the patient's own bone marrow, or with cells processed by more routine that minimally purifies the cells. The study goal is to see if the ALD-301 cells are more effective in generating new small blood vessels to improve the circulation to the affected leg.
Detailed description
Patients will be recruited who have critical limb ischemia with pain at rest. The study will select patients for treatment and follow them for three months after intervention. The treatment will consist of drawing about 2/3 of a cup of bone marrow from the patient's hip bone, then processing the collected bone marrow will be as follows:
- The test group's bone marrow will be processed and sorted to identify the aldehyde dehydrogenase bright ALDH-br stem and progenitor cells (ALD-301). These cells will be injected into the calf muscle of the patient in clinic.
- The control group will have the same amount of bone marrow collected but it will undergo a simpler process to isolate the mononuclear cells from the whole bone marrow, removing most of the red cells and granulocytes from cell preparation for injection.
The patients will be monitored for adverse events related to this process to determine the safety of the approach. They will also be tested at intervals during the study to compare baseline values of each patient with the post-treatment values of:
- ankle-brachial index of systolic blood pressure
- the transcutaneous oxygen measurements obtained from the skin of the treated leg
- the patient's perception of his/her quality of life as measured by two different, validated questionnaires
- Measurements of of heel/foot ulcers, if present, to monitor degree of healing if it occurs
- the patient's perception of his/her level of pain in the leg
The patients will receive a call at 6 months to report on additional life events following the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 2 | Experimental | Procedure: ALDH-br bone marrow cells vs. mononuclear bone marrow cellsUnfractionated Autologous Mononuclear Bone Marrow |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients 18 years of age or greater with atherosclerotic vascular disease that is viewed as not readily amenable to reconstructive surgery and Rutherford Category 4 ischemia (ischemic rest pain) and Rutherford Category 5 ischemia (ulceration or tissue necrosis) and by the judgment of their referring physician are not reasonable candidates for revascularization options of either percutaneous balloon angioplasty or a surgical revascularization.
- Objective evidence of severe peripheral arterial disease will include an ankle brachial index (ABI) of less than 0.5, or, in the case of patients who have vessels calcified and thereby "non-compressible" vessels metatarsal pulse volume recording (PVR) that is flat or barely pulsatile in the diseased limb on two consecutive examinations performed at least one week apart.
- Patients competent to give informed consent.
- No active malignant disease that could involve the bone marrow, or history of treatment of malignant disease that could have damaged the bone marrow.
- Before being accepted for the study the patient must be screened for human immunodeficiency virus, hepatitis B virus, hepatitis C virus, human transmissible spongiform encephalopathy, including Creutzfeldt-Jacob Disease, Treponema pallidum, and have a negative standard infectious disease panel including a CMV PCR test.
Key exclusion criteria (17 listed)
- Patients with poorly controlled diabetes mellitus (HbA1C > 8%)
- Patients with renal insufficiency (creatinine > 2.5).
- Patients with evidence of infectious disease as determined by e. above or other medical findings.
- Pregnant women (women capable of childbearing must have a negative pregnancy test).
- Patients with cognitive impairments.
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 |
|---|---|---|
| ALDH-br bone marrow cells vs. mononuclear bone marrow cellsSurgery | Procedure or surgery | 2 |
Primary outcome
adverse events
Time frame: 6 months
ankle-brachial systolic pressure index
Time frame: 3 mo
transcutaneous oxygen value (mm Torr)
Time frame: 3 mo
quality of life (questionnaires)
Time frame: 3 mo
4 secondary outcomes
size of lower extremity ulcer(s)
Time frame: 3 mo
peripheral nerve conduction exam
Time frame: 3 mo
level of pain at rest (questionnaire)
Time frame: 3 mo
limb clinical status
Time frame: 3 mo
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2009.
- Derived from this study: PubMed 21594960Perin EC, Silva G, Gahremanpour A, Canales J, Zheng Y, Cabreira-Hansen MG, Mendelsohn F, Chronos N, Haley R, Willerson JT, Annex BH. A randomized, controlled study of autologous therapy with bone marrow-derived aldehyde dehydrogenase bright cells in patients with critical limb ischemia. Catheter Cardiovasc Interv. 2011 Dec 1;78(7):1060-7. doi: 10.1002/ccd.23066. Epub 2011 May 18.
- Sponsor's WebsiteLink provided by the sponsor.
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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.
Emerson C Perin, M.D., Ph.D. principal investigator
Stem Cell Center, Texas Heart Institute, St Luke's Episcopal Hospital, 6770 Bertner , Suite 1020 Texas Medical Center,Houston, Texas 77030
Robert Mitchell, MD principal investigator
Duke University
Michael Murphy, MD principal investigator
University of Indiana at Indianapolis
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ALDH-br bone marrow cells vs. mononuclear bone marrow cells in people with Critical Limb Ischemia and Peripheral Arterial Disease, run by Aldagen at 5 sites 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 6 inclusion and 17 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: finished, as of the sponsor's last update on 14 May 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
adverse events (time frame: 6 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00392509, which also lists 1 linked publication.
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 14 May 2009.