Critical Limb IschemiaPhase 2NCT01745744
Application of Cell Regeneration Therapy With Mesenchymal Stem Cells From Adipose Tissue in Critical Chronic Ischemic Syndrome of Lower Limbs (CLI) in Nondiabetic Patients.
A Phase 2 study testing Mesenchymal stem cells from adipose tissue in people with Critical Limb Ischemia, run by Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud at 2 sites in Spain.
Trial summary
Clinical trial phase I / II, prospective, multicenter, open, randomized, parallel-groups controlled by two levels of dose to assess the safety and feasibility of the infusion of mesenchymal stem cells from adipose tissue administered intra-arterially in nondiabetic patients with chronic ischemia of lower limbs (CLI)… Read more about this study
- Who is it for?
- Ages 18 to 89 years
- Conditions the study is for
- Critical Limb Ischemia
- What is being tested?
- Mesenchymal stem cells from adipose tissue
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 2 sitesSpain
- Study dates
- Feb 2011to Jul 2018
- Phase
- Phase 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 to 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients of both sexes aged ≥ 18 and ≤ 89 years.
- Nondiabetic.
- Infrapopliteal atherosclerotic vascular disease of severe grade with either severe claudication or Rutherford-Becker grade II-III-IV, of at least one lower limb. It is defined critical ischemia of the lower limb as persistent/recurrent pain requiring analgesia and / or non-healing present ulcers > 4 weeks, with no evidence of improvement with conventional therapies and / or walking test (stress test) between 1-6 minutes in two exercise tests separated by at least 2 weeks and / or ankle-brachial index at rest <0.8.
- Inability of surgical or endovascular revascularization as recommended by the TransAtlantic InterSociety Consensus (TASC).
- Failure in the revascularization surgery performed at least 30 days before, with persistence or entry in critical ischemia phase.
- Life expectancy> 2 years.
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- Not expected major amputation in the limb to treat in the next 12 months after inclusion.
- Normal biochemical parameters defined by:
- Leukocytes ≥ 3000
- Neutrophils ≥ 1500
- Platelets ≥ 100,000
- Aspartate aminotransferase (AST) / Alanine aminotransferase (ALT) ≤ 2.5 standard range institution
- Creatinine ≤ 2.5 mg / dl.
- Patients give their written informed consent to participate in the study.
- Women of childbearing potential must have negative results on a pregnancy test done at the time of inclusion in the study and agree to use a medically approved method of contraception for the duration of the study.
Who cannot join
- History of malignancy or hematologic disease (myeloproliferative disease, myelodysplastic syndrome or leukemia) in the last two years.
- Patients with uncontrolled hypertension (defined as blood pressure> 180/110 on more than one occasion).
- Severe heart failure (New York Heart Association class IV) or ejection fraction of the left ventricle less than 30%.
- Patients with malignant ventricular arrhythmias or unstable angina at the time of infusion.
- Diagnosis of deep vein thrombosis in the previous 3 months.
- Active infection or wet gangrene at day of infusion of Mesenchymal Stem Cells from Adipose Tissue.
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- Concomitant therapy including hyperbaric oxygen. It is allowed the use of antiplatelet agents.
- Body mass index>40 kg/m2.
- Patients with a diagnosis of alcoholism at the time of inclusion.
- Untreated proliferative retinopathy.
- Concomitant disease that reduces life expectancy to less than a year.
- Predicted impossibility to obtain a biopsy providing 10 g of adipose tissue.
- human immunodeficiency virus, hepatitis B virus or hepatitis C virus.
- Difficulty in monitoring.
- Stroke or myocardial infarction within the last 3 months.
- Anemia (hemoglobin <7.9 mg / dl).
- Leukopenia.
- Thrombocytopenia (<100,000 platelets / ul).
- Pregnant women or women of childbearing age who do not have adequate contraception.
- Patients who participated in a clinical trial within the last 3 months prior to inclusion in this clinical trial.
Trial locations and contacts
2 sites in 1 country.
Spain2 sites
Hospital San Lazaro
Seville, 41009
University Hospital Virgen Macarena
Seville, 41009
About this study
Official title: Clinical Trial Phase I / II, Multicentre, Open, Randomized Study of the Use of Mesenchymal Stem Cells From Adipose Tissue (CeTMAd) as Cell Regeneration Therapy in Critical Chronic Ischemic Syndrome of Lower Limb in Nondiabetic Patients.
Clinical trial phase I / II, prospective, multicenter, open, randomized, parallel-groups controlled by two levels of dose to assess the safety and feasibility of the infusion of mesenchymal stem cells from adipose tissue administered intra-arterially in nondiabetic patients with chronic ischemia of lower limbs (CLI) and no possibility of revascularization.
Read the detailed description
A prospective, multicenter, open, randomized, parallel-group controlled study for two levels of dose.
The study population will consist of 30 non-diabetic patients with critical chronic ischemia in at least one of the lower limbs (CLI) and without possibility of revascularization, from whom results can clinically be evaluable, of whom, 20 patients will be included in the experimental group (10 for each dose level) and 10 in the control group.
In each of the two dose levels to be used in the study, 15 patients will be included, who will be randomized to the experimental group or the control group according to a distribution 2:1 (2 patients in the experimental group and 1 in control group), thus at each dose level, we will have 10 patients in the experimental group (treated with mesenchymal cells of adipose tissue) and 5 patients in the control group (conventional treatment, including the use of prostaglandins per protocol).
Patients who are randomized to experimental treatment Group with CeTMAd may receive one of the following dose levels:
- 0.5x106 cells / kg of patient weight
- 1x106 cells / kg of patient weight
The recruitment will be done with escalating doses, starting at the lower dose. To switch to the higher dose will require a favorable opinion of the Ethics Committee of the H. Universitario Virgen Macarena to evaluate the clinical status of patients and therapeutic safety and study procedures.
Patients who are randomized to the treatment control group will continue with conventional treatment which they were performing at the time of inclusion in the study (including the use of prostaglandins as protocol).
STUDY OBJECTIVE: To evaluate the safety and feasibility of regenerative treatment with mesenchymal stem cells from adipose tissue (CeTMAd), administered intraarterial in nondiabetic patients with chronic critical ischemia of at least one lower limb without possibilities of revascularization or alternative therapies. We will analyze the complications from regenerative therapy and / or study procedures.
- Main objectives:
- Security: It will be studied the possible complications due to the procedure in the first 24 hours of administration of CeTMAd, 1 month, 3 months, 6 months, 9 months and 12 months.
- Efficiency: It will be studied the generation of new vessels (vasculogenesis) and enhancement of collateral circulation (angiogenesis / arteriogenesis).
- Secondary objectives:
It will be studied the evolution of ankle brachial index, transcutaneous oxygen pressure, degree of Rutherford-Becker, ulcer size, calf perimeter, the score of pain and intermittent claudication (walking test).
Duration of the clinical trial: From the infusion to the patient of the Mesenchymal Stem Cells from Adipose Tissue to the end of the monitoring, there will be 12 months.
- Conditions
- Critical Limb Ischemia
- Being tested
- Mesenchymal stem cells from adipose tissue
- 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.
Mesenchymal stem cells from adipose tissueOther
- Infusion of mesenchymal stem cells from adipose tissue administered intraarterially: 0.5x106 cells / kg of patient weight and 1x106 cells / kg of patient weight.
| Study group | Role | What they receive |
|---|---|---|
| Low dose | Experimental | - Infusion of mesenchymal stem cells from adipose tissue: 0.5x106 cells / kg of patient weight. Receives: Other: Mesenchymal stem cells from adipose tissue |
| High dose | Experimental | - Infusion of mesenchymal stem cells from adipose tissue: 1x106 cells / kg of patient weight. Receives: Other: Mesenchymal stem cells from adipose tissue |
| Control | No intervention | Conventional treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of adverse events and serious adverse events
Number of adverse events and serious adverse events: 24h administration of CeTMAd, 1 month, 3 months, 6 months, 9 months and 12 months.
Measured: 12 months.
Secondary outcomes (1)
Evolution of chronic critical ischemia
Parameters:Ankle brachial index, transcutaneous oxygen pressure, degree of Rutherford-Becker, larger ulcer size (as Texas classification), twin perimeter, score of pain and intermittent claudication (walking test).
Measured: 1 month, 3 months, 6 months, 9 months and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2012 (estimated)
- Study startFeb 2011
- Primary completionJul 2018
- Study completionJul 2018
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
- Sponsor type
- University, hospital or other
- Collaborators
- Iniciativa Andaluza en Terapias Avanzadas
- Responsible party
- Sponsor
- Investigators
- Rafael J. Ruiz-Salmerón, Principal investigator, Hemodynamics Unit. Hospital Universitario Virgen Macarena.Antonio de la Cuesta, Principal investigator, Chronic Critical Ischemia Unit. San Lazaro Hospital.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01745744
- Sponsor's protocol ID
- CeTMAd/ICC/2009
- Other IDs
- 2009-013554-32, 2009
- Status last verified
- Jul 2018
- First submitted
- 3 Dec 2012
- Last updated
- 9 Jul 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Trial Phase I / II, Multicentre, Open, Randomized Study of the Use of Mesenchymal Stem Cells From Adipose Tissue (CeTMAd) as Cell Regeneration Therapy in Critical Chronic Ischemic Syndrome of Lower Limb in Nondiabetic Patients.
- ClinicalTrials.gov ID
- NCT01745744
- Acronym / sponsor ID
- CeTMAd/ICC/2009
- Conditions
- Critical Limb Ischemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y SaludUniversity, hospital or other
- Collaborators
- Iniciativa Andaluza en Terapias Avanzadas
- Study start
- Feb 2011
- Primary completion
- Jul 2018 (actual)
- Study completion
- Jul 2018 (actual)
- First posted
- 10 Dec 2012 (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.
Clinical trial phase I / II, prospective, multicenter, open, randomized, parallel-groups controlled by two levels of dose to assess the safety and feasibility of the infusion of mesenchymal stem cells from adipose tissue administered intra-arterially in nondiabetic patients with chronic ischemia of lower limbs (CLI) and no possibility of revascularization.
Detailed description
A prospective, multicenter, open, randomized, parallel-group controlled study for two levels of dose.
The study population will consist of 30 non-diabetic patients with critical chronic ischemia in at least one of the lower limbs (CLI) and without possibility of revascularization, from whom results can clinically be evaluable, of whom, 20 patients will be included in the experimental group (10 for each dose level) and 10 in the control group.
In each of the two dose levels to be used in the study, 15 patients will be included, who will be randomized to the experimental group or the control group according to a distribution 2:1 (2 patients in the experimental group and 1 in control group), thus at each dose level, we will have 10 patients in the experimental group (treated with mesenchymal cells of adipose tissue) and 5 patients in the control group (conventional treatment, including the use of prostaglandins per protocol).
Patients who are randomized to experimental treatment Group with CeTMAd may receive one of the following dose levels:
- 0.5x106 cells / kg of patient weight
- 1x106 cells / kg of patient weight
The recruitment will be done with escalating doses, starting at the lower dose. To switch to the higher dose will require a favorable opinion of the Ethics Committee of the H. Universitario Virgen Macarena to evaluate the clinical status of patients and therapeutic safety and study procedures.
Patients who are randomized to the treatment control group will continue with conventional treatment which they were performing at the time of inclusion in the study (including the use of prostaglandins as protocol).
STUDY OBJECTIVE: To evaluate the safety and feasibility of regenerative treatment with mesenchymal stem cells from adipose tissue (CeTMAd), administered intraarterial in nondiabetic patients with chronic critical ischemia of at least one lower limb without possibilities of revascularization or alternative therapies. We will analyze the complications from regenerative therapy and / or study procedures.
- Main objectives:
- Security: It will be studied the possible complications due to the procedure in the first 24 hours of administration of CeTMAd, 1 month, 3 months, 6 months, 9 months and 12 months.
- Efficiency: It will be studied the generation of new vessels (vasculogenesis) and enhancement of collateral circulation (angiogenesis / arteriogenesis).
- Secondary objectives:
It will be studied the evolution of ankle brachial index, transcutaneous oxygen pressure, degree of Rutherford-Becker, ulcer size, calf perimeter, the score of pain and intermittent claudication (walking test).
Duration of the clinical trial: From the infusion to the patient of the Mesenchymal Stem Cells from Adipose Tissue to the end of the monitoring, there will be 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Low dose | Experimental | Other: Mesenchymal stem cells from adipose tissue- Infusion of mesenchymal stem cells from adipose tissue: 0.5x106 cells / kg of patient weight. |
| High dose | Experimental | Other: Mesenchymal stem cells from adipose tissue- Infusion of mesenchymal stem cells from adipose tissue: 1x106 cells / kg of patient weight. |
| Control | No intervention | –Conventional treatment |
Who may qualify
- Ages
- 18 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patients of both sexes aged ≥ 18 and ≤ 89 years.
- Nondiabetic.
- Infrapopliteal atherosclerotic vascular disease of severe grade with either severe claudication or Rutherford-Becker grade II-III-IV, of at least one lower limb. It is defined critical ischemia of the lower limb as persistent/recurrent pain requiring analgesia and / or non-healing present ulcers > 4 weeks, with no evidence of improvement with conventional therapies and / or walking test (stress test) between 1-6 minutes in two exercise tests separated by at least 2 weeks and / or ankle-brachial index at rest <0.8.
- Inability of surgical or endovascular revascularization as recommended by the TransAtlantic InterSociety Consensus (TASC).
- Failure in the revascularization surgery performed at least 30 days before, with persistence or entry in critical ischemia phase.
Key exclusion criteria (20 listed)
- History of malignancy or hematologic disease (myeloproliferative disease, myelodysplastic syndrome or leukemia) in the last two years.
- Patients with uncontrolled hypertension (defined as blood pressure> 180/110 on more than one occasion).
- Severe heart failure (New York Heart Association class IV) or ejection fraction of the left ventricle less than 30%.
- Patients with malignant ventricular arrhythmias or unstable angina at the time of infusion.
- Diagnosis of deep vein thrombosis in the previous 3 months.
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 |
|---|---|---|
| Mesenchymal stem cells from adipose tissue- Infusion of mesenchymal stem cells from adipose tissue administered intraarterially: 0.5x106 cells / kg of patient weight and 1x106 cells / kg of patient weight. | Other | High dose, Low dose |
Primary outcome
Number of adverse events and serious adverse events
Time frame: 12 months.
Number of adverse events and serious adverse events: 24h administration of CeTMAd, 1 month, 3 months, 6 months, 9 months and 12 months.
1 secondary outcome
Evolution of chronic critical ischemia
Time frame: 1 month, 3 months, 6 months, 9 months and 12 months
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 9 Jul 2018.
- Andalusian Molecular Biology and Regenerative Medicine CentreLink 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.
Rafael J. Ruiz-Salmerón principal investigator
Hemodynamics Unit. Hospital Universitario Virgen Macarena.
Antonio de la Cuesta principal investigator
Chronic Critical Ischemia Unit. San Lazaro Hospital.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mesenchymal stem cells from adipose tissue in people with Critical Limb Ischemia, run by Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud at 2 sites in Spain.
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 15 inclusion and 20 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 9 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Spain. 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 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?
Number of adverse events and serious adverse events (time frame: 12 months.). 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 9 Jul 2018.