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Critical Limb IschemiaPhase 2/3SCELTANCT02454231

Monocentric Trial: Stem Cell Emergency Life Threatening Limbs Arteriopathy (SCELTA)

A Phase 2/3 study testing Transplantation of circulating CD14+CD34+cells and Transplantation of BM MNC in people with Critical Limb Ischemia, run by University of Florence at 1 site in Italy.

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

The investigators designed a randomized clinical trial (stem cell emergency life threatening arteriopathy or SCELTA) to compare the therapeutic efficacy of the auto-transplant of enriched circulating EPCs (ECEPCs) with auto-transplant of BM-MNCs. Read more about this study

Who is it for?
Ages 40 years and older
Conditions the study is for
Critical Limb Ischemia
What is being tested?
Transplantation of circulating CD14+CD34+cells and Transplantation of BM MNC
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
1 siteItaly
Study dates
Sep 2009to Oct 2015
Phase
Phase 2/3
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 40 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Eligible patients were men and women aged more than 40 years with a diagnosis of CLI due to atherosclerosis of the lower extremities, as defined by the presence of persistent rest pain requiring systemic and continued analgesic treatment in the last 15 days and/or the presence of trophic lesions imputable to the occluding arteriopathy, an ankle-brachial Index (ABI) < 0.40 (with systolic ankle pressure < 50-70 Hg mm), a toe/brachial index (TBI) < 0.40 (with big toe systolic pressure < 30-50 Hg mm), and a transcutaneous oxygen pressure (TC pO2) < 30 Hg mm.
  • The patient was considered as eligible for the treatment and enrolled only after the demonstration that intravascular or surgical re-vascularization was not possible, as revealed by ecography and angio-CAT, or when the patient refused to undergo surgical treatments and after having obtained his/her written informed consensus.

Who cannot join

  • not atherosclerotic CLI,
  • myocardial infarction occurrence in the 6 months;
  • cardiac failure of III-IV class NYHA;
  • ejection fraction lower than 40%;
  • arterial hypertension (>160/100 Hg mm) uncontrolled despite the usage of two anti-hypertensive drugs;
  • presence of current or chronic severe infectious diseases;
Show all 14Show fewer
  • osteomyelitis;
  • diabetes with glycate hemoglobin > 7.5;
  • proliferative diabetic retinopathy;
  • hemorrhagic disorders;
  • non-atherosclerotic arteriopathy;
  • chronic airway insufficiency (p02 <65 Hg mm, pCO2 > 0.50 Hg mm);
  • renal failure (creatinine > 2mg/dl);
  • contraindications or intolerance to contrast media for radiologic imaging

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Azienda Ospedaliero-Universitaria Careggi

    Florence, Tuscany, 50134

Other trials in Italy

About this study

Official title: Monocentric Randomized Study for the Therapy of Critic Limb Ischemia With Bone Marrow- or Peripheral Blood-derived Stem Cells

The investigators designed a randomized clinical trial (stem cell emergency life threatening arteriopathy or SCELTA) to compare the therapeutic efficacy of the auto-transplant of enriched circulating EPCs (ECEPCs) with auto-transplant of BM-MNCs. ECEPCs, obtained by immunoselection of CD14+ and CD34+ cells, or BM-MNCs, were injected intramuscularly in the affected limb of patients with critical limb ischemia (CLI).

Read the detailed description

Peripheral arterial disease comprises a clinical spectrum that extends from no symptoms to presentation with critical limb ischemia (CLI), which is a very invalidating condition characterized by rest pain, march inability, trophic lesions and unavoidable progression to major amputations, which are burdened by a high mortality in the first year. The pathophysiology of CLI often associates with a defect in the development of collateral vessels and angiogenesis, a process which refers to the formation of new blood vessels into tissue, due to circulating endothelial progenitor cells (EPCs) and vascular progenitor cells. In the last few years, significant improvement of this condition has been reported following bone marrow (BM) autotransplant or autotransplant of peripheral EPCs mobilized from BM through the injection of granulocyte-colony stimulatory factor (G-CSF). In a previous study, the investigators found that individually variable proportions of circulating CD14+ cells expressed low levels of CD34 (CD14+CD34low) and revealed the functional phenotype of EPCs. The investigators therefore designed a monocentric randomized clinical trial to compare the therapeutic efficacy of BM autotransplant with the autotransplant of a population of circulating CD34+ and CD14+CD34low enriched by a closed sterile immunomagnetic system (enriched circulating EPCs or ECEPCs), without a previous EPC mobilization from BM.

Patients will be evaluated for clinical parameters and ABI, TBI, TCp02 before autotransplant and at three follow-up times after the autotransplant (4, 24 and 52 weeks); also angio-TAC of legs, capillaroscopy, and photoplethysmography will be evaluated at 4, and even at 52 weeks.

Being tested
Transplantation of circulating CD14+CD34+cells, Transplantation of BM MNC
Keywords
EPC, CD34+, CD14+CD34low
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.

  • Transplantation of circulating CD14+CD34+cellsBiological

    intramuscular injection of circulating EPC at leg level

  • Transplantation of BM MNCBiological

    intramuscular injection of BM MNC at leg level

Study groups in NCT02454231
Study groupRoleWhat they receive
peripheral blood EPC injectionExperimentalNot described
Receives: Biological: Transplantation of circulating CD14+CD34+cells
bone marrow MNC injectionActive comparatorNot described
Receives: Biological: Transplantation of BM MNC

What is being measured

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

  1. Safety as measured by evaluation of any adverse event temporary correlated with the treatment

    Evaluation of any adverse event temporary correlated with the treatment

    Measured: 52 weeks of follow-up

  2. Changes in ischemic leg perfusion from baseline

    Improvement of leg perfusion as assessed by values of Time to Pick (TTP) evaluated by ultrasound tools

    Measured: 4, 22, 52 weeks of follow-up

Secondary outcomes (10)

  1. Improvement of Mean values of the transcutaneous partial oxygen pressure (TCP02)

    Improvement of mean values of the transcutaneous partial oxygen pressure of at least 20%

    Measured: 4, 22, 52 weeks of follow-up

  2. Improvement of mean values of ankle brachial pressure index (ABI)

    improvement (at least 25% increase) of Mean values of ankle brachial pressure index

    Measured: 4, 22, 52 weeks of follow-up

  3. Improvement of vessel anatomical status

    Improvement of leg vascularization as assessed by color Doppler ultrasound

    Measured: 4, 22, 52 weeks of follow-up

  4. Improvement of leg perfusion

    Improvement of leg perfusion as assessed by plethysmography characterization

    Measured: 4, 22, 52 weeks of follow-up

  5. Improvement of vessel anatomical status

    Improvement of leg vascularization as assessed by Angio-CT, defined as presence of new vessels

    Measured: 4, 22, 52 weeks of follow-up

  6. Quality of life Improvement

    Quality of life, as assessed by the disease-specific ST22 and SF36 questionaries

    Measured: -28, 0, 28 weeks of follow-up

  7. improvement of rest pain

    Rest pain as evaluated by visual analogue pain scale (VAS)

    Measured: 4, 22, 52 weeks of follow-up

  8. Improvement of trophic limb lesions

    Mean score of trophic limb lesions, as evaluated according to Wagner international grade

    Measured: 4, 22, 52 weeks of follow-up

  9. Reduction of numbers of major amputation (amputation free survival )

    Reduction of numbers of major amputation compared with untreated patients

    Measured: 4, 22, 52 weeks of follow-up

  10. improvement of microvascular anatomy

    evaluation of microvascular anatomy as assessed by capillaroscopy

    Measured: 4, 22, 52 weeks of follow-up

Timeline

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

  1. First posted27 May 2015 (estimated)
  2. Study startSep 2009
  3. Primary completionMay 2015
  4. Study completionOct 2015

Resources

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02454231
Sponsor's protocol ID
UFlorence
Acronym
SCELTA
Status last verified
May 2017
First submitted
19 May 2015
Last updated
9 May 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Weitz JI, Byrne J, Clagett GP, Farkouh ME, Porter JM, Sackett DL, Strandness DE Jr, Taylor LM. Diagnosis and treatment of chronic arterial insufficiency of the lower extremities: a critical review. Circulation. 1996 Dec 1;94(11):3026-49. doi: 10.1161/01.cir.94.11.3026. No abstract available.

    PubMed 8941154

  • Gregg EW, Sorlie P, Paulose-Ram R, Gu Q, Eberhardt MS, Wolz M, Burt V, Curtin L, Engelgau M, Geiss L; 1999-2000 national health and nutrition examination survey. Prevalence of lower-extremity disease in the US adult population >=40 years of age with and without diabetes: 1999-2000 national health and nutrition examination survey. Diabetes Care. 2004 Jul;27(7):1591-7. doi: 10.2337/diacare.27.7.1591.

    PubMed 15220233

  • Curb JD, Masaki K, Rodriguez BL, Abbott RD, Burchfiel CM, Chen R, Petrovitch H, Sharp D, Yano K. Peripheral artery disease and cardiovascular risk factors in the elderly. The Honolulu Heart Program. Arterioscler Thromb Vasc Biol. 1996 Dec;16(12):1495-500. doi: 10.1161/01.atv.16.12.1495.

    PubMed 8977454

  • Meijer WT, Grobbee DE, Hunink MG, Hofman A, Hoes AW. Determinants of peripheral arterial disease in the elderly: the Rotterdam study. Arch Intern Med. 2000 Oct 23;160(19):2934-8. doi: 10.1001/archinte.160.19.2934.

    PubMed 11041900

  • Melillo E, Nuti M, Bongiorni L, Golgini E, Balbarini A. [Major and minor amputation rates and lower critical limb ischemia: the epidemiological data of western Tuscany]. Ital Heart J Suppl. 2004 Oct;5(10):794-805. Italian.

    PubMed 15615351

  • Inglese L, Graziani L, Tarricone R. [Percutaneous treatment of peripheral obstructive arteriopathy: the reasons for a choice]. Ital Heart J Suppl. 2000 Sep;1(9):1138-47. Italian.

    PubMed 11140282

  • Dzau VJ, Gnecchi M, Pachori AS, Morello F, Melo LG. Therapeutic potential of endothelial progenitor cells in cardiovascular diseases. Hypertension. 2005 Jul;46(1):7-18. doi: 10.1161/01.HYP.0000168923.92885.f7. Epub 2005 Jun 13.

    PubMed 15956118

  • Ikenaga S, Hamano K, Nishida M, Kobayashi T, Li TS, Kobayashi S, Matsuzaki M, Zempo N, Esato K. Autologous bone marrow implantation induced angiogenesis and improved deteriorated exercise capacity in a rat ischemic hindlimb model. J Surg Res. 2001 Apr;96(2):277-83. doi: 10.1006/jsre.2000.6080.

    PubMed 11266284

  • Kalka C, Masuda H, Takahashi T, Kalka-Moll WM, Silver M, Kearney M, Li T, Isner JM, Asahara T. Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3422-7. doi: 10.1073/pnas.97.7.3422.

    PubMed 10725398

  • Iwaguro H, Yamaguchi J, Kalka C, Murasawa S, Masuda H, Hayashi S, Silver M, Li T, Isner JM, Asahara T. Endothelial progenitor cell vascular endothelial growth factor gene transfer for vascular regeneration. Circulation. 2002 Feb 12;105(6):732-8. doi: 10.1161/hc0602.103673.

    PubMed 11839630

  • Iba O, Matsubara H, Nozawa Y, Fujiyama S, Amano K, Mori Y, Kojima H, Iwasaka T. Angiogenesis by implantation of peripheral blood mononuclear cells and platelets into ischemic limbs. Circulation. 2002 Oct 8;106(15):2019-25. doi: 10.1161/01.cir.0000031332.45480.79.

    PubMed 12370229

  • Tateishi-Yuyama E, Matsubara H, Murohara T, Ikeda U, Shintani S, Masaki H, Amano K, Kishimoto Y, Yoshimoto K, Akashi H, Shimada K, Iwasaka T, Imaizumi T; Therapeutic Angiogenesis using Cell Transplantation (TACT) Study Investigators. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet. 2002 Aug 10;360(9331):427-35. doi: 10.1016/S0140-6736(02)09670-8.

    PubMed 12241713

  • Masuda H, Asahara T. Post-natal endothelial progenitor cells for neovascularization in tissue regeneration. Cardiovasc Res. 2003 May 1;58(2):390-8. doi: 10.1016/s0008-6363(02)00785-x.

    PubMed 12757873

  • Romagnani P, Annunziato F, Liotta F, Lazzeri E, Mazzinghi B, Frosali F, Cosmi L, Maggi L, Lasagni L, Scheffold A, Kruger M, Dimmeler S, Marra F, Gensini G, Maggi E, Romagnani S. CD14+CD34low cells with stem cell phenotypic and functional features are the major source of circulating endothelial progenitors. Circ Res. 2005 Aug 19;97(4):314-22. doi: 10.1161/01.RES.0000177670.72216.9b. Epub 2005 Jul 14.

    PubMed 16020753

  • Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell. 2003 May 30;113(5):643-55. doi: 10.1016/s0092-8674(03)00392-1.

    PubMed 12787505

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Transplantation of circulating CD14+CD34+cells and Transplantation of BM MNC in people with Critical Limb Ischemia, run by University of Florence at 1 site in Italy.

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 2 inclusion and 14 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 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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?

Safety as measured by evaluation of any adverse event temporary correlated with the treatment (time frame: 52 weeks of follow-up). 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?

On the ClinicalTrials.gov record for NCT02454231, which also lists 20 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 9 May 2017.

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SCELTA Clinical Trial NCT02454231 | AzTrials