Critical Limb Ischemia (CLI)Phase 1/2NCT00987363
Intraarterial Infusion of Autologous Bone Marrow in Diabetic Patients With Chronic Ischemia of Lower Limbs (CLI) no Revascularization
A Phase 1/2 study testing Intraarterial infusion of autologous bone marrow cells in people with Critical Limb Ischemia (CLI) and Diabetic Foot, run by Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud at 5 sites in Spain.
Trial summary
The aim of the study is to evaluate the safety and feasibility of autologous bone marrow mononuclear cells autologous administered intra-arterially in the affected limb of diabetic patients with chronic critical ischemia of the lower limbs (CLI) without possibility of revascularization or other therapeutic… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Critical Limb Ischemia (CLI), Diabetic Foot
- What is being tested?
- Intraarterial infusion of autologous bone marrow cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 5 sitesSpain
- Study dates
- Jul 2009to Mar 2013
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 1 or 2 diabetes mellitus
- Grade II-III Rutherford-Becker peripheral vascular disease affecting at least one limb
- Arterial obstruction(s) located at infrapopliteal level
- No options of endoarterial or surgical revascularization
- Life expectancy more than 2 years
- Unlikelihood of major amputation of the leg during the next 12 months
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- Normal analytical parameters in blood: leucocytes>3000/micoL, neutrophils>1500 microL, Hb>10mg/dl, platelets>100000 microL,AST and ALT<2.5 standard value, creatinin<2.5 mg/dl
- Written informed consent
- Negative pregnancy test when applicable
Who cannot join
- History of neoplasm or hematological disease
- Uncontrolled high blood pressure (>180/110)
- Severe cardiac insufficiency (NYHA IV) or ejection fraction<30%
- Malignant ventricular arrythmia
- Deep venous thrombosis during the last 3 months
- Active bacterial infection
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- Treatment with hyperbaric oxygen, vasoactive drugs, Cox-II inhibitors or antiangiogenic agents
- Body mass index > 40
- Alcoholism
- Proliferative retinopathy
- HIV, HBV or HCV viral infection
- Stroke or myocardial infarction during the last 3 months
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Spain5 sites
Hospital Universitario Reina Sofia
Córdoba, 14004
Hospital Universitario San Cecilio
Granada, 18012
Hospital Universitario Virgen de la Nieves
Granada, 18014
Hospital Universitario Morales Meseguer
Murcia, 30008
Hospital Universitario Virgen del Rocio
Seville, 41013
About this study
Official title: Phase II Clinical Trial of Therapeutic Angiogenesis With Mononuclear Cells Autologous Bone Marrow in Patients With Chronic Ischemia Diabetics Critical Limb (CLI) no Revascularization.
The aim of the study is to evaluate the safety and feasibility of autologous bone marrow mononuclear cells autologous administered intra-arterially in the affected limb of diabetic patients with chronic critical ischemia of the lower limbs (CLI) without possibility of revascularization or other therapeutic alternatives.
The trial hypothesis we propose consists of mononuclear cells of bone marrow providing progenitor cells with regenerative capacity and secrete also several angiogenic factors, and their implantation into ischemic tissues with both elements should contribute to angiogenesis and tissue regeneration with recovery of the circulation in the affected limb
Read the detailed description
Phase II Clinical Trial, a prospective, multicenter, open, randomized, parallel-group controlled with three dose levels.
The study population will consist of a total of 60 diabetic patients with chronic critical ischemia of one leg (CLI) and no possibility of revascularization. In the experimental group will include a total of 45 patients divided into three dose levels, 15 patients in each level (increasing doses of mononuclear cells of bone marrow evenly) and 15 patients in control group (no cell therapy). Patients will be randomly assigned to either the control group or to any of the three experimental groups in which the dose of mononuclear cells of bone marrowo will be:
- Group 1(15 patients): no cell therapy.
- Group 2(15 patients): 1x108 mononuclear cells of bone marrow
- Gropu 3(15 patients): 5x108 mononuclear cells of bone marrow
- Group 4(15 patients): 1x109 mononuclear cells of bone marrow The cell therapy medicinal product shall be administered in all cases intraarterially.
Patients were evaluated by clinical, radiological and angiologist methods. This is a randomized controlled trial in which the safety and feasibility of cell therapy medicinal product shall be measured by comparing the response variables after treatment compared to baseline prior to implementation. Secondarily the results obtained are compared with each of the dose groups.
Patients will receive in a concomitant way the drug treatment established by the good practice, so it would certainly be possible that some improvement occurs due to drug treatment.
The primary variable is the improvement in the vascularización of the treated limb determined by clinical, angiologic and angiographic parameters.
It is estimated that the inclusion period lasts between twelve and eighteen months with twelve months follow-up. Therefore the total study duration range between twenty-four and thirty months from the inclusion of the first patient to the end of the follow-up of the last patient included.
Objectives of the study:
- Main objective: To evaluate the safety and feasibility of mononuclear cells of autologous bone marrow administered intra-arterially in the affected limb of diabetic patients with chronic critical ischemia of the lower limbs without possibility of revascularization or other therapeutic alternatives.
Secondary objectives:
- Conditions
- Critical Limb Ischemia (CLI), Diabetic Foot
- Being tested
- Intraarterial infusion of autologous bone marrow cells
- Keywords
- critical limb ischemia (CLI), diabetic foot, bone marrow derived mononuclear cells, cell therapy
- Medical subject headings
- Chronic Limb-Threatening Ischemia, Diabetic Foot
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intraarterial infusion of autologous bone marrow cellsOther
Autologous bone marrow-derived mononuclear cells will be infused by an intraarterial catheter into de ischemic limb. The number of infused cells will be 1x10 E8, 5x10E8 and 1x10 E9 in the low,intermediate and high dose arms respectively
| Study group | Role | What they receive |
|---|---|---|
| Low dose (1x10 E8) | Experimental | Dose of 1x10 E8 autologous bone marrow-derived mononuclear cells Receives: Other: Intraarterial infusion of autologous bone marrow cells |
| Intermediate dose (5x10 E8) | Experimental | Dose of 5x10 E8 autologous bone marrow-derived mononuclear cells Receives: Other: Intraarterial infusion of autologous bone marrow cells |
| High dose (1x10 E9) | Experimental | Dose of 1x10 E9 autologous bone marrow-derived mononuclear cells Receives: Other: Intraarterial infusion of autologous bone marrow cells |
| Control | No intervention | Conventional treatment established by the good clinical practice |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of adverse events
Measured: 24 h, 1,3 ,6 ,9 and 12 months
AngioRNM and/or AngioTC changes
Measured: baseline and 12 months
Secondary outcomes (1)
Clinically objective improvement in the ischemic limb
(Ankle/brachial index, transcutaneous oxygen pressure, degree of Rutherford-Becker, greater ulcer size and perimeter calf muscle)
Measured: 1, 3, 6, 9 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 posted30 Sep 2009 (estimated)
- Study startJul 2009
- Primary completionMar 2013
- Study completionMar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Critical Limb Ischemia (CLI)Studies 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
- None (open label)
- Enrolment
- 60 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
- Inmaculada Herrera, MD, PhD, Study chair, Hospital Universitario Reina Sofia de CordobaFrancisco Tadeo Gomez, MD, PhD, Principal investigator, Hospital Virgen del RocioJose Patricio Linares, MD, PhD, Principal investigator, Hospital Universitario San CecilioDiego Martinez, MD, PhD, Principal investigator, Hospital Universitario Morales MesseguerVicente García, MD,PhD, Principal investigator, University Hospital Virgen de las NievesAntonio Chacon, MD, PhD, Principal investigator, Hospital General Universitario Reina Sofía de Murcia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00987363
- Sponsor's protocol ID
- CMMo/ICPD/2008
- Other IDs
- 2008-004064-39, 2008
- Status last verified
- Nov 2014
- First submitted
- 29 Sep 2009
- Last updated
- 16 Mar 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Clinical Trial of Therapeutic Angiogenesis With Mononuclear Cells Autologous Bone Marrow in Patients With Chronic Ischemia Diabetics Critical Limb (CLI) no Revascularization.
- ClinicalTrials.gov ID
- NCT00987363
- Acronym / sponsor ID
- CMMo/ICPD/2008
- Conditions
- Critical Limb Ischemia (CLI), Diabetic Foot
- Keywords
- critical limb ischemia (CLI), diabetic foot, bone marrow derived mononuclear cells, cell therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 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
- Jul 2009
- Primary completion
- Mar 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 30 Sep 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 aim of the study is to evaluate the safety and feasibility of autologous bone marrow mononuclear cells autologous administered intra-arterially in the affected limb of diabetic patients with chronic critical ischemia of the lower limbs (CLI) without possibility of revascularization or other therapeutic alternatives.
The trial hypothesis we propose consists of mononuclear cells of bone marrow providing progenitor cells with regenerative capacity and secrete also several angiogenic factors, and their implantation into ischemic tissues with both elements should contribute to angiogenesis and tissue regeneration with recovery of the circulation in the affected limb
Detailed description
Phase II Clinical Trial, a prospective, multicenter, open, randomized, parallel-group controlled with three dose levels.
The study population will consist of a total of 60 diabetic patients with chronic critical ischemia of one leg (CLI) and no possibility of revascularization. In the experimental group will include a total of 45 patients divided into three dose levels, 15 patients in each level (increasing doses of mononuclear cells of bone marrow evenly) and 15 patients in control group (no cell therapy). Patients will be randomly assigned to either the control group or to any of the three experimental groups in which the dose of mononuclear cells of bone marrowo will be:
- Group 1(15 patients): no cell therapy.
- Group 2(15 patients): 1x108 mononuclear cells of bone marrow
- Gropu 3(15 patients): 5x108 mononuclear cells of bone marrow
- Group 4(15 patients): 1x109 mononuclear cells of bone marrow The cell therapy medicinal product shall be administered in all cases intraarterially.
Patients were evaluated by clinical, radiological and angiologist methods. This is a randomized controlled trial in which the safety and feasibility of cell therapy medicinal product shall be measured by comparing the response variables after treatment compared to baseline prior to implementation. Secondarily the results obtained are compared with each of the dose groups.
Patients will receive in a concomitant way the drug treatment established by the good practice, so it would certainly be possible that some improvement occurs due to drug treatment.
The primary variable is the improvement in the vascularización of the treated limb determined by clinical, angiologic and angiographic parameters.
It is estimated that the inclusion period lasts between twelve and eighteen months with twelve months follow-up. Therefore the total study duration range between twenty-four and thirty months from the inclusion of the first patient to the end of the follow-up of the last patient included.
Objectives of the study:
- Main objective: To evaluate the safety and feasibility of mononuclear cells of autologous bone marrow administered intra-arterially in the affected limb of diabetic patients with chronic critical ischemia of the lower limbs without possibility of revascularization or other therapeutic alternatives.
Secondary objectives:
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Low dose (1x10 E8) | Experimental | Other: Intraarterial infusion of autologous bone marrow cellsDose of 1x10 E8 autologous bone marrow-derived mononuclear cells |
| Intermediate dose (5x10 E8) | Experimental | Other: Intraarterial infusion of autologous bone marrow cellsDose of 5x10 E8 autologous bone marrow-derived mononuclear cells |
| High dose (1x10 E9) | Experimental | Other: Intraarterial infusion of autologous bone marrow cellsDose of 1x10 E9 autologous bone marrow-derived mononuclear cells |
| Control | No intervention | –Conventional treatment established by the good clinical practice |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Type 1 or 2 diabetes mellitus
- Grade II-III Rutherford-Becker peripheral vascular disease affecting at least one limb
- Arterial obstruction(s) located at infrapopliteal level
- No options of endoarterial or surgical revascularization
- Life expectancy more than 2 years
Key exclusion criteria (12 listed)
- History of neoplasm or hematological disease
- Uncontrolled high blood pressure (>180/110)
- Severe cardiac insufficiency (NYHA IV) or ejection fraction<30%
- Malignant ventricular arrythmia
- Deep venous thrombosis during the last 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 |
|---|---|---|
| Intraarterial infusion of autologous bone marrow cellsAutologous bone marrow-derived mononuclear cells will be infused by an intraarterial catheter into de ischemic limb. The number of infused cells will be 1x10 E8, 5x10E8 and 1x10 E9 in the low,intermediate and high dose arms respectively | Other | High dose (1x10 E9), Intermediate dose (5x10 E8), Low dose (1x10 E8) |
Primary outcome
Number of adverse events
Time frame: 24 h, 1,3 ,6 ,9 and 12 months
AngioRNM and/or AngioTC changes
Time frame: baseline and 12 months
1 secondary outcome
Clinically objective improvement in the ischemic limb
Time frame: 1, 3, 6, 9 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 16 Mar 2016.
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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.
Inmaculada Herrera, MD, PhD study chair
Hospital Universitario Reina Sofia de Cordoba
Francisco Tadeo Gomez, MD, PhD principal investigator
Hospital Virgen del Rocio
Jose Patricio Linares, MD, PhD principal investigator
Hospital Universitario San Cecilio
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 Intraarterial infusion of autologous bone marrow cells in people with Critical Limb Ischemia (CLI) and Diabetic Foot, run by Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud at 5 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 9 inclusion and 12 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 16 Mar 2016. 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 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 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?
Number of adverse events (time frame: 24 h, 1,3 ,6 ,9 and 12 months). The study lists 2 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 16 Mar 2016.