Critical Limb Ischemia (CLI)Phase 2NCT01408381

Intra-arterial Infusion of Autologous Bone Marrow Mononuclear Cells in Non-diabetic Patients With Critical Limb Ischemia (CLI).

A Phase 2 study testing Intraarterial Infusion of Autologous Bone Marrow Mononuclear Cells in people with Critical Limb Ischemia (CLI), run by Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud at 5 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Phase II Clinical Trial, a prospective, multicenter, open, randomized, parallel-group controlled with three levels of dose. The hypothesis of the test we propose is that the mononuclear cells of bone marrow provide progenitor cells with regenerative capacity and besides secrete several angiogenic factors, and their… Read more about this study

Who is it for?: Ages 18 to 89 years
Conditions the study is for: Critical Limb Ischemia (CLI)
What is being tested?: Intraarterial Infusion of Autologous Bone Marrow Mononuclear Cells
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 38 participants
Where: 5 sitesSpain
Study dates: Jan 2011to Jun 2015
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.
Non-diabetic.
Infrapopliteal atherosclerotic vascular disease with severe to severe claudication or Rutherford-Becker grade I-3, II, III, in at least one lower limb. The chronic critical ischemia of the lower limb is defined as persistent / recurring pain requiring analgesia and / or non-healing ulcers present> 4 weeks, with no evidence of improvement with conventional therapies and / or walking test (stress test) between 1-6 minutes two exercise tests separated by at least 2 weeks and / or ankle-brachial index at rest <0.8.
Inability to endovascular or surgical revascularization as recommended by the TransAtlantic Inter-Society Consensus (TASC).
Failure of the revascularization surgical performed at least 30 days before, either persistently 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 6 months after inclusion.
Normal laboratory 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 should give their written informed consent to participate in the study.
Women of childbearing potential must have negative results on a pregnancy test following standard procedures for each hospital performed at the time of inclusion in the study and agree to use a medically approved method of contraception through the duration of the study.

Who cannot join

History of malignancy or hematologic disease (myeloproliferative disease, myelodysplastic syndrome or leukemia)
Patients with uncontrolled hypertension (defined as blood pressure> 180/110 on more than one occasion).
Severe heart failure (New York Heart Association IV).
Patients with malignant ventricular arrhythmias or unstable angina.
Diagnosis of deep vein thrombosis in the previous 3 months.
Active infection or gangrene wet day infusion of mononuclear bone marrow cells.

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Corporal mass index (BMI)> 40 kg/m2.
Patients with a diagnosis of alcoholism at the time of inclusion.
Proliferative retinopathy.

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

Spain5 sites

University Hospital Puerta del Mar
Cadiz, Cádiz, 11009
University Hospital Reina Sofía
Córdoba, Cordoba, 14004
University Hospital Virgen de las Nieves
Granada, Granada, 18014
University Hopistal Carlos Haya
Málaga, Málaga, 29010
University Hospital Nuestra Señora de Valme
Seville, Sevilla, 41014

Other trials in Spain

About this study

Official title: Multicenter Phase II, Randomized Open Clinical Trial on the Therapeutic Use of Intra-arterial Infusion of Autologous Bone Marrow Mononuclear Cells in Non-diabetic Patients With Critical Chronic Ischemia of Lower Limbs (CLI).

Phase II Clinical Trial, a prospective, multicenter, open, randomized, parallel-group controlled with three levels of dose.

The hypothesis of the test we propose is that the mononuclear cells of bone marrow provide progenitor cells with regenerative capacity and besides secrete 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

The study population will consist of a total of 44 non-diabetic patients with chronic critical ischemia in at least one of their lower limbs (CLI) and without possibility of revascularization. In the experimental group will be included a total of 33 patients divided into three levels of dose, 11 patients in each level (increasing dose of mononuclear cells from autologous bone marrow) and other 11 patients in control group.

11 patients in group 1 will not receive cell therapy, and they will only receive conventional treatment, acting as a control group.
11 patients in group 2 will receive 1x108 autologous bone marrow mononuclear cells.
11 patients in group 3 will receive 5x108 autologous bone marrow mononuclear cells.
11 patients in group 4 will receive 1x109 autologous bone marrow mononuclear cells.

The cell therapy drug will be administered intra-arterially in all cases. Patients will be evaluated by clinical, radiological and angiological methods (ankle / brachial pressure index, transcutaneous oxygen pressure, perimeter calf muscle, presence of ulcers, oximetry and digital arteriography).

Patients will receive concomitant drug treatment established by the good clinical practice, so undoubtedly it could be possible that some improvement occurs due to drug treatment.

It is estimated that the inclusion period is approximately 42 months, and the follow-up of each patient of six months. Therefore the total duration of the study will be about forty eight months from the entry of the first patient to the end of the follow-up period of the last patient included.

The primary variable is the improvement in the vascularisation of the treated limb determined by clinical, angiographic and angiologist parameters.

Study objectives :

Main objective: To evaluate the safety and feasibility of the autotransplantation of autologous bone marrow mononuclear cells administered intra-arterially in non-diabetic patients with critical chronic ischemia of the lower limbs without possibility of either revascularization or other therapeutic alternatives.

Secondary objectives:

To compare the effect of three increasing dose of mononuclear cells from autologous bone marrow in the recovery of clinical, angiographic angiologist parameters in non-diabetic patients with critical chronic ischemia of lower limbs to a control group that will have been applied to a conventional treatment.
To analyze complications from regenerative therapy itself, from the route of administration and / or study procedures.

Conditions: Critical Limb Ischemia (CLI)
Being tested: Intraarterial Infusion of Autologous Bone Marrow Mononuclear Cells
Keywords: Critical Limb Ischemia (CLI), Cell Therapy, Bone marrow mononuclear cells
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.

Intraarterial Infusion of Autologous Bone Marrow Mononuclear 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 1x108, 5x108 and 1x109 low, intermediate and high dose in the arms respectively.

Study groups in NCT01408381
Study group	Role	What they receive
Control	No intervention	No cell therapy
Low dose	Experimental	Intraarterial Infusion of Autologous Bone Marrow Mononuclear Cells: 1 x 108 Receives: Other: Intraarterial Infusion of Autologous Bone Marrow Mononuclear Cells
Intermediate dose	Experimental	Intraarterial Infusion of Autologous Bone Marrow Mononuclear Cells: 5 x 108 Receives: Other: Intraarterial Infusion of Autologous Bone Marrow Mononuclear Cells
High dose	Experimental	Intraarterial Infusion of Autologous Bone Marrow Mononuclear Cells: 1 x 109 Receives: Other: Intraarterial Infusion of Autologous Bone Marrow Mononuclear Cells

What is being measured

The primary outcome is the main question the study is designed to answer.

Adverse events
Measured: 6 months

Secondary outcomes (6)

Ankle-brachial index
Measured: 1 month, 3 months, 6 months
Transcutaneous oxygen pressure (TcO2)
Measured: 1 month, 3 months, 6 months
Greater ulcer size
Ulcer diameter will be recorded
Measured: 1 month, 3 months, 6 months
Degree of Rutherford-Becker
Measured: 1 month, 3 months, 6 months
Perimeter calf muscle
Measured: 1 month, 3 months, 6 months
Presence of faster opacity in infrapopliteal vessels at 6 months compared with the basal situation of the patient.
Measured: 1 month, 3 month, 6 month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2011Jun 2015

First posted3 Aug 2011 (estimated)
Study startJan 2011
Primary completionJun 2015
Study completionJun 2015

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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 38 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01408381
Sponsor's protocol ID: CMMo/ICC/2009
Other IDs: 2009-013636-20, 2009
Status last verified: Mar 2016
First submitted: 1 Aug 2011
Last updated: 16 Mar 2016
Results posted: No
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
FastWire REvascularisation of Extremities, (For LOWer Limbs) - FREEFLOW
Chronic Total Occlusion of Artery of the Extremities
Active, not recruitingObservational study
An All-Comers Observational Study of the MicroStent™ Peripheral Vascular Stent System in Subjects With Peripheral Arterial Disease
Peripheral Arterial Disease, Critical Lower Limb Ischemia
Recruiting
FAZA PET/MRI in CLI Patients Pre and Post Revascularization
Critical Limb Ischemia
Recruiting
PROMISE III: Percutaneous Deep Vein Arterialization for the Treatment of Late-Stage Chronic Limb-Threatening Ischemia
Critical Limb Ischemia, Chronic Limb-Threatening Ischemia
Active, not recruiting
LIFE-BTK PK Sub-study
Critical Limb Ischemia (CLI)

All Critical Limb Ischemia (CLI) trials

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: Multicenter Phase II, Randomized Open Clinical Trial on the Therapeutic Use of Intra-arterial Infusion of Autologous Bone Marrow Mononuclear Cells in Non-diabetic Patients With Critical Chronic Ischemia of Lower Limbs (CLI).
ClinicalTrials.gov ID: NCT01408381
Acronym / sponsor ID: CMMo/ICC/2009
Conditions: Critical Limb Ischemia (CLI)
Keywords: Critical Limb Ischemia (CLI), Cell Therapy, Bone marrow mononuclear cells
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 38 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: Jan 2011
Primary completion: Jun 2015 (actual)
Study completion: Jun 2015 (actual)
First posted: 3 Aug 2011 (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.

Phase II Clinical Trial, a prospective, multicenter, open, randomized, parallel-group controlled with three levels of dose.

Detailed description

11 patients in group 1 will not receive cell therapy, and they will only receive conventional treatment, acting as a control group.
11 patients in group 2 will receive 1x108 autologous bone marrow mononuclear cells.
11 patients in group 3 will receive 5x108 autologous bone marrow mononuclear cells.
11 patients in group 4 will receive 1x109 autologous bone marrow mononuclear cells.

Patients will receive concomitant drug treatment established by the good clinical practice, so undoubtedly it could be possible that some improvement occurs due to drug treatment.

The primary variable is the improvement in the vascularisation of the treated limb determined by clinical, angiographic and angiologist parameters.

Study objectives :

Main objective: To evaluate the safety and feasibility of the autotransplantation of autologous bone marrow mononuclear cells administered intra-arterially in non-diabetic patients with critical chronic ischemia of the lower limbs without possibility of either revascularization or other therapeutic alternatives.

Secondary objectives:

To compare the effect of three increasing dose of mononuclear cells from autologous bone marrow in the recovery of clinical, angiographic angiologist parameters in non-diabetic patients with critical chronic ischemia of lower limbs to a control group that will have been applied to a conventional treatment.
To analyze complications from regenerative therapy itself, from the route of administration and / or study procedures.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Control	No intervention	–No cell therapy
Low dose	Experimental	Other: Intraarterial Infusion of Autologous Bone Marrow Mononuclear CellsIntraarterial Infusion of Autologous Bone Marrow Mononuclear Cells: 1 x 108
Intermediate dose	Experimental	Other: Intraarterial Infusion of Autologous Bone Marrow Mononuclear CellsIntraarterial Infusion of Autologous Bone Marrow Mononuclear Cells: 5 x 108
High dose	Experimental	Other: Intraarterial Infusion of Autologous Bone Marrow Mononuclear CellsIntraarterial Infusion of Autologous Bone Marrow Mononuclear Cells: 1 x 109

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.
Non-diabetic.
Infrapopliteal atherosclerotic vascular disease with severe to severe claudication or Rutherford-Becker grade I-3, II, III, in at least one lower limb. The chronic critical ischemia of the lower limb is defined as persistent / recurring pain requiring analgesia and / or non-healing ulcers present> 4 weeks, with no evidence of improvement with conventional therapies and / or walking test (stress test) between 1-6 minutes two exercise tests separated by at least 2 weeks and / or ankle-brachial index at rest <0.8.
Inability to endovascular or surgical revascularization as recommended by the TransAtlantic Inter-Society Consensus (TASC).
Failure of the revascularization surgical performed at least 30 days before, either persistently or entry in critical ischemia phase.

Key exclusion criteria (9 listed)

History of malignancy or hematologic disease (myeloproliferative disease, myelodysplastic syndrome or leukemia)
Patients with uncontrolled hypertension (defined as blood pressure> 180/110 on more than one occasion).
Severe heart failure (New York Heart Association IV).
Patients with malignant ventricular arrhythmias or unstable angina.
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
Intraarterial Infusion of Autologous Bone Marrow Mononuclear CellsAutologous bone marrow-derived mononuclear cells will be infused by an intraarterial catheter into de ischemic limb. The number of infused cells will be 1x108, 5x108 and 1x109 low, intermediate and high dose in the arms respectively.	Other	High dose, Intermediate dose, Low dose

Primary outcome

Adverse events
Time frame: 6 months

6 secondary outcomes

Ankle-brachial index
Time frame: 1 month, 3 months, 6 months
Transcutaneous oxygen pressure (TcO2)
Time frame: 1 month, 3 months, 6 months
Greater ulcer size
Time frame: 1 month, 3 months, 6 months
Degree of Rutherford-Becker
Time frame: 1 month, 3 months, 6 months
Perimeter calf muscle
Time frame: 1 month, 3 months, 6 months
Presence of faster opacity in infrapopliteal vessels at 6 months compared with the basal situation of the patient.
Time frame: 1 month, 3 month, 6 month

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.
Andalusian Molecular Biology and Regenerative Medicine CentreLink provided by the sponsor.

Related trials for Critical Limb Ischemia (CLI)

Recruiting
FastWire REvascularisation of Extremities, (For LOWer Limbs) - FREEFLOW
Chronic Total Occlusion of Artery of the Extremities
Active, not recruitingObservational study
An All-Comers Observational Study of the MicroStent™ Peripheral Vascular Stent System in Subjects With Peripheral Arterial Disease
Peripheral Arterial Disease, Critical Lower Limb Ischemia
Recruiting
FAZA PET/MRI in CLI Patients Pre and Post Revascularization
Critical Limb Ischemia
Recruiting
PROMISE III: Percutaneous Deep Vein Arterialization for the Treatment of Late-Stage Chronic Limb-Threatening Ischemia
Critical Limb Ischemia, Chronic Limb-Threatening Ischemia
Active, not recruiting
LIFE-BTK PK Sub-study
Critical Limb Ischemia (CLI)

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

University Hospital Reina Sofía, Córdoba.

Antonio Chacon, MD, PhD principal investigator

University Hospital Reina Sofia, Córdoba

Diego Martinez, MD, PhD principal investigator

University Hospital Morales Meseguer, Murcia

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 9 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 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?

Adverse events (time frame: 6 months). 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 NCT01408381.

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.