Diabetic Patients With Critic Ischemia in Lower Limbs Who Are Administered With CD133+ Cells Mobilized by G-CSFPhase 1/2NCT00765050

A Prospective, Open, Non-randomized Phase I/II Study of Therapeutic Angiogenesis in Diabetic Patients With Critic Ischemia of Lower Limbs While Administering Positive CD133 Mobilized With G-CSF

A Phase 1/2 study testing CD133+ cells transplant in people with Diabetic Patients With Critic Ischemia in Lower Limbs Who Are Administered With CD133+ Cells Mobilized by G-CSF, run by PETHEMA Foundation at 5 sites in Spain.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

The primary objective is to analyze the safety and efficacy of CD133+ cells, obtained from peripheral blood in the treatment of diabetic patients with critic ischemia in lower limbs. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Diabetic Patients With Critic Ischemia in Lower Limbs Who Are Administered With CD133+ Cells Mobilized by G-CSF
What is being tested?: CD133+ cells transplant
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 13 participants
Where: 5 sitesSpain
Study dates: Jan 2009to Oct 2012
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 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

According to the investigator opinion, patient is able to carry out with all the clinical trial requirements
Patient must volunteer sign the inform consent before any study specific test, that is not part of the common patient attention, is performed. Patient must know that he/she can abandon the study at any time with no damage to his/her posterior attention
Age 18 to 75
A diagnosis of chronic critic ischemia of the lower limbs
Diabetes Mellitus active
III or IV stages (Fontaine classification): resting pain, ulcer or minor gangrene with no major amputation
General contraindication or local inoperability or refractory/progression after previous surgical treatment, according to the investigator criteria
If female reproductive potential, negative pregnancy test

Who cannot join

Pregnant or currently breast feeding women
Acute myocardial infarction within the last 3 years
Non re-vascular unstable angina pectoris
History of ischemia stroke within the last 3 years
Neoplasia at the time of inclusion or Chemotherapy or Radiotherapy treatment in the last 5 years
Chronic renal insufficiency

Show all 11Show fewer

G-CSF contraindication
A non well controlled serious concomitant disease
History of serious thrombotic episodes within the past 3 years
Patients who have received other investigational therapy within 30 days previous to the study inclusion
Patients currently in other clinical trial or receiving any other investigational agent

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

Spain5 sites

Hospital Virgen de la Arrixaca
Murcia
Clínica Universitaria de Navarra
Pamplona
Hospital Clínico Universitario
Salamanca
Hospital Joan XIII de
Tarragona
Hospital Clínico Universitario
Valladolid

Other trials in Spain

About this study

The primary objective is to analyze the safety and efficacy of CD133+ cells, obtained from peripheral blood in the treatment of diabetic patients with critic ischemia in lower limbs.

The secondary objectives are:

To determine the safety of the intramuscular administration of CD133+ cells that have been mobilized from peripheral blood.
To determine the CD133+ capacity to increase the re-vascularization at lower limbs in diabetic patients with critic ischemia in the lower limbs.
To evaluate the patient global health condition using the notified results of the SF-36 questionnaires completed by patients

Read the detailed description

A total of up to 20 diabetic patients with critic ischemia of lower limbs will be included in the study. Patients will be administered with CD133+ cells, that previously have been obtained of their peripheral blood after mobilization with G-CSF

The study is divided in three phases:

Pre-treatment (previous 4 weeks of CD133+ cells mobilization). Treatment (cells mobilization, CD133+ transplant, 24 hours after infusion visit, 4, 12 and 24 weeks after transplant visits) Follow-up (9 and 12 months after transplant visits)

Conditions: Diabetic Patients With Critic Ischemia in Lower Limbs Who Are Administered With CD133+ Cells Mobilized by G-CSF
Being tested: CD133+ cells transplant
Keywords: Cellular therapy, CD133+
Medical subject headings: Macular Dystrophy, Retinal, 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CD133+ cells transplantBiological
intramuscular administration of CD133+ cells that have been mobilized from peripheral blood.

Study groups in NCT00765050
Study group	Role	What they receive
CD133+ cells	Experimental	CD133+ cells, obtained from peripheral blood in the treatment of diabetic patients with critic ischemia in lower limbs. Receives: Biological: CD133+ cells transplant

What is being measured

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

analyze the safety and efficacy of CD133+ cells, obtained from peripheral blood in the treatment of diabetic patients with critic ischemia in lower limbs.
Measured: 12 months

Secondary outcomes (3)

To determine the safety of the intramuscular administration of CD133+ cells that have been mobilized from peripheral blood
Measured: 2 months
To determine the CD133+ capacity to increase the re-vascularization at lower limbs in diabetic patients with critic ischemia in the lower limbs
Measured: 12 months
To evaluate the patient global health condition using the notified results of the SF-36 questionnaires completed by patients
Measured: 12 months

Timeline

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

Jan 2009Oct 2012

First posted2 Oct 2008 (estimated)
Study startJan 2009
Primary completionOct 2012
Study completionOct 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (43)Papers the sponsor has linked to this study.
Other trials for Diabetic Patients With Critic Ischemia in Lower Limbs Who Are Administered With CD133+ Cells Mobilized by G-CSFStudies 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: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 13 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00765050
Sponsor's protocol ID: 2008-000693-20
Other IDs: 2008
Status last verified: Apr 2014
First submitted: 1 Oct 2008
Last updated: 7 Apr 2014
Results posted: No
Data monitoring committee: Yes

Publications

Second European Consensus Document on chronic critical leg ischemia. Circulation. 1991 Nov;84(4 Suppl):IV1-26. No abstract available.
PubMed 1834364
Mohler ER 3rd. Therapy insight: peripheral arterial disease and diabetes--from pathogenesis to treatment guidelines. Nat Clin Pract Cardiovasc Med. 2007 Mar;4(3):151-62. doi: 10.1038/ncpcardio0823.
PubMed 17330127
Dormandy JA, Rutherford RB. Management of peripheral arterial disease (PAD). TASC Working Group. TransAtlantic Inter-Society Consensus (TASC). J Vasc Surg. 2000 Jan;31(1 Pt 2):S1-S296. No abstract available.
PubMed 10666287
Perez Encinas M, Fernandez MA, Martin ML, Calvo MV, Gomez-Alonso A, Dominguez-Gil A, Lozano F. Multicriteria decision analysis for determining drug therapy for intermittent claudication. Methods Find Exp Clin Pharmacol. 1998 Jun;20(5):425-31. doi: 10.1358/mf.1998.20.5.485704.
PubMed 9701781
Ramos M, Almazan A, Lozano F, Gomez-Alonso A. Phenol lumbar sympathectomy in severe arterial disease of the lower limbs: a hemodynamic study. Int Surg. 1983 Apr-Jun;68(2):127-30.
PubMed 6885290
Almeida J, Bueno C, Alguero MC, Sanchez ML, Canizo MC, Fernandez ME, Vaquero JM, Laso FJ, Escribano L, San Miguel JF, Orfao A. Extensive characterization of the immunophenotype and pattern of cytokine production by distinct subpopulations of normal human peripheral blood MHC II+/lineage- cells. Clin Exp Immunol. 1999 Dec;118(3):392-401. doi: 10.1046/j.1365-2249.1999.01078.x.
PubMed 10594557
Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997 Feb 14;275(5302):964-7. doi: 10.1126/science.275.5302.964.
PubMed 9020076
Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, Kearne M, Magner M, Isner JM. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res. 1999 Aug 6;85(3):221-8. doi: 10.1161/01.res.85.3.221.
PubMed 10436164
Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H, Inai Y, Silver M, Isner JM. VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J. 1999 Jul 15;18(14):3964-72. doi: 10.1093/emboj/18.14.3964.
PubMed 10406801
Canizo MC, Lozano F, Gonzalez-Porras JR, Barros M, Lopez-Holgado N, Briz E, Sanchez-Guijo FM. Peripheral endothelial progenitor cells (CD133 +) for therapeutic vasculogenesis in a patient with critical limb ischemia. One year follow-up. Cytotherapy. 2007;9(1):99-102. doi: 10.1080/14653240601034708.
PubMed 17354105
de Wynter EA, Buck D, Hart C, Heywood R, Coutinho LH, Clayton A, Rafferty JA, Burt D, Guenechea G, Bueren JA, Gagen D, Fairbairn LJ, Lord BI, Testa NG. CD34+AC133+ cells isolated from cord blood are highly enriched in long-term culture-initiating cells, NOD/SCID-repopulating cells and dendritic cell progenitors. Stem Cells. 1998;16(6):387-96. doi: 10.1002/stem.160387.
PubMed 9831864
Durdu S, Akar AR, Arat M, Sancak T, Eren NT, Ozyurda U. Autologous bone-marrow mononuclear cell implantation for patients with Rutherford grade II-III thromboangiitis obliterans. J Vasc Surg. 2006 Oct;44(4):732-9. doi: 10.1016/j.jvs.2006.06.023. Epub 2006 Aug 22.
PubMed 16926085
Fadini GP, Sartore S, Albiero M, Baesso I, Murphy E, Menegolo M, Grego F, Vigili de Kreutzenberg S, Tiengo A, Agostini C, Avogaro A. Number and function of endothelial progenitor cells as a marker of severity for diabetic vasculopathy. Arterioscler Thromb Vasc Biol. 2006 Sep;26(9):2140-6. doi: 10.1161/01.ATV.0000237750.44469.88. Epub 2006 Jul 20.
PubMed 16857948
Flamme I, Risau W. Induction of vasculogenesis and hematopoiesis in vitro. Development. 1992 Oct;116(2):435-9. doi: 10.1242/dev.116.2.435.
PubMed 1286617
Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971 Nov 18;285(21):1182-6. doi: 10.1056/NEJM197111182852108. No abstract available.
PubMed 4938153

Study at a glance

From the registry record, last updated by the sponsor on 7 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Prospective, Open, Non-randomized Phase I/II Study of Therapeutic Angiogenesis in Diabetic Patients With Critic Ischemia of Lower Limbs While Administering Positive CD133 Mobilized With G-CSF
ClinicalTrials.gov ID: NCT00765050
Acronym / sponsor ID: 2008-000693-20
Conditions: Diabetic Patients With Critic Ischemia in Lower Limbs Who Are Administered With CD133+ Cells Mobilized by G-CSF
Keywords: Cellular therapy, CD133+
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Terminated
Enrolment: 13 participants (actual)
Lead sponsor: PETHEMA FoundationUniversity, hospital or other
Study start: Jan 2009
Primary completion: Oct 2012 (actual)
Study completion: Oct 2012 (actual)
First posted: 2 Oct 2008 (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 primary objective is to analyze the safety and efficacy of CD133+ cells, obtained from peripheral blood in the treatment of diabetic patients with critic ischemia in lower limbs.

The secondary objectives are:

To determine the safety of the intramuscular administration of CD133+ cells that have been mobilized from peripheral blood.
To determine the CD133+ capacity to increase the re-vascularization at lower limbs in diabetic patients with critic ischemia in the lower limbs.
To evaluate the patient global health condition using the notified results of the SF-36 questionnaires completed by patients

Detailed description

The study is divided in three phases:

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
CD133+ cells	Experimental	Biological: CD133+ cells transplantCD133+ cells, obtained from peripheral blood in the treatment of diabetic patients with critic ischemia in lower limbs.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

According to the investigator opinion, patient is able to carry out with all the clinical trial requirements
Patient must volunteer sign the inform consent before any study specific test, that is not part of the common patient attention, is performed. Patient must know that he/she can abandon the study at any time with no damage to his/her posterior attention
Age 18 to 75
A diagnosis of chronic critic ischemia of the lower limbs
Diabetes Mellitus active

Key exclusion criteria (11 listed)

Pregnant or currently breast feeding women
Acute myocardial infarction within the last 3 years
Non re-vascular unstable angina pectoris
History of ischemia stroke within the last 3 years
Neoplasia at the time of inclusion or Chemotherapy or Radiotherapy treatment in the last 5 years

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
CD133+ cells transplantintramuscular administration of CD133+ cells that have been mobilized from peripheral blood.	Biological	CD133+ cells

Primary outcome

analyze the safety and efficacy of CD133+ cells, obtained from peripheral blood in the treatment of diabetic patients with critic ischemia in lower limbs.
Time frame: 12 months

3 secondary outcomes

To determine the safety of the intramuscular administration of CD133+ cells that have been mobilized from peripheral blood
Time frame: 2 months
To determine the CD133+ capacity to increase the re-vascularization at lower limbs in diabetic patients with critic ischemia in the lower limbs
Time frame: 12 months
To evaluate the patient global health condition using the notified results of the SF-36 questionnaires completed by patients
Time frame: 12 months

Results and safety

The study was stopped early. Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2014.
Background: PubMed 1834364Second European Consensus Document on chronic critical leg ischemia. Circulation. 1991 Nov;84(4 Suppl):IV1-26. No abstract available.
Background: PubMed 17330127Mohler ER 3rd. Therapy insight: peripheral arterial disease and diabetes--from pathogenesis to treatment guidelines. Nat Clin Pract Cardiovasc Med. 2007 Mar;4(3):151-62. doi: 10.1038/ncpcardio0823.
Background: PubMed 10666287Dormandy JA, Rutherford RB. Management of peripheral arterial disease (PAD). TASC Working Group. TransAtlantic Inter-Society Consensus (TASC). J Vasc Surg. 2000 Jan;31(1 Pt 2):S1-S296. No abstract available.
Background: PubMed 9701781Perez Encinas M, Fernandez MA, Martin ML, Calvo MV, Gomez-Alonso A, Dominguez-Gil A, Lozano F. Multicriteria decision analysis for determining drug therapy for intermittent claudication. Methods Find Exp Clin Pharmacol. 1998 Jun;20(5):425-31. doi: 10.1358/mf.1998.20.5.485704.
Background: PubMed 6885290Ramos M, Almazan A, Lozano F, Gomez-Alonso A. Phenol lumbar sympathectomy in severe arterial disease of the lower limbs: a hemodynamic study. Int Surg. 1983 Apr-Jun;68(2):127-30.
Background: PubMed 10594557Almeida J, Bueno C, Alguero MC, Sanchez ML, Canizo MC, Fernandez ME, Vaquero JM, Laso FJ, Escribano L, San Miguel JF, Orfao A. Extensive characterization of the immunophenotype and pattern of cytokine production by distinct subpopulations of normal human peripheral blood MHC II+/lineage- cells. Clin Exp Immunol. 1999 Dec;118(3):392-401. doi: 10.1046/j.1365-2249.1999.01078.x.
Background: PubMed 9020076Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997 Feb 14;275(5302):964-7. doi: 10.1126/science.275.5302.964.
Background: PubMed 10436164Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, Kearne M, Magner M, Isner JM. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res. 1999 Aug 6;85(3):221-8. doi: 10.1161/01.res.85.3.221.
Background: PubMed 10406801Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H, Inai Y, Silver M, Isner JM. VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J. 1999 Jul 15;18(14):3964-72. doi: 10.1093/emboj/18.14.3964.
Background: PubMed 17354105Canizo MC, Lozano F, Gonzalez-Porras JR, Barros M, Lopez-Holgado N, Briz E, Sanchez-Guijo FM. Peripheral endothelial progenitor cells (CD133 +) for therapeutic vasculogenesis in a patient with critical limb ischemia. One year follow-up. Cytotherapy. 2007;9(1):99-102. doi: 10.1080/14653240601034708.
Background: PubMed 9831864de Wynter EA, Buck D, Hart C, Heywood R, Coutinho LH, Clayton A, Rafferty JA, Burt D, Guenechea G, Bueren JA, Gagen D, Fairbairn LJ, Lord BI, Testa NG. CD34+AC133+ cells isolated from cord blood are highly enriched in long-term culture-initiating cells, NOD/SCID-repopulating cells and dendritic cell progenitors. Stem Cells. 1998;16(6):387-96. doi: 10.1002/stem.160387.
Background: PubMed 16926085Durdu S, Akar AR, Arat M, Sancak T, Eren NT, Ozyurda U. Autologous bone-marrow mononuclear cell implantation for patients with Rutherford grade II-III thromboangiitis obliterans. J Vasc Surg. 2006 Oct;44(4):732-9. doi: 10.1016/j.jvs.2006.06.023. Epub 2006 Aug 22.
Spanish association of HaematologyLink provided by the sponsor.

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.

Mª Consuelo Del Cañizo, Dr study chair

Hospital Clínico de Salamanca

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 8 inclusion and 11 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 7 Apr 2014. 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 was stopped early. 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?

analyze the safety and efficacy of CD133+ cells, obtained from peripheral blood in the treatment of diabetic patients with critic ischemia in lower limbs. (time frame: 12 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 NCT00765050, which also lists 43 linked publications.

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 7 Apr 2014.