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Limb IschemiaPhase 2NCT04466007

Safety and Efficacy of Allogeneic Adipose Tissue Mesenchymal Stem Cells in Diabetic Patients With Critical Limb Ischemia

A Phase 2 study testing High dose allogeneic mesenchymal stromal cells and Low dose allogeneic mesenchymal stromal cells in people with Limb Ischemia and Diabetic Foot, run by Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz at 10 sites in Spain.

Completed

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

Official record
Search all trials

Trial summary

Phase II national, multicenter, double-blind, randomized, placebo-controlled, phase-3 clinical trial of 3 parallel groups. Read more about this study

Who is it for?
Ages 40 to 90 years
Conditions the study is for
Limb Ischemia, Diabetic Foot
What is being tested?
High dose allogeneic mesenchymal stromal cells and Low dose allogeneic mesenchymal stromal cells
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
90 participants
Where
10 sitesSpain
Study dates
11 Jan 2021to 5 Dec 2024
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 40 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must meet ALL of the following criteria to be included in the study:
  • Patients of both sexes.
  • Age between 40 and 90 years.
  • Severe grade vascular arteriosclerosis (category RB 4 and 5 mono or bilateral).
  • Impossibility of surgical or endovascular revascularization or failure in revascularization surgery performed, at least 30 days before inclusion in the study, defining failure as direct non-arrival of vessels to the plantar arch.
  • Normal biochemical parameters defined by:
Show all 15Show fewer
  • Leukocytes> 3000 / mm3
  • Neutrophils> 1500 / mm3
  • Platelets> 100,000 / mm3
  • AST / ALT <2.5x upper limit of normal
  • In patients with an ischemic ulcer, it must be stable for at least 1 week.
  • Patients under conventional medical treatment for CLI.
  • Women of childbearing age must obtain a negative result in a urine pregnancy test performed at the time of inclusion in the study and commit to using an effective contraceptive method during their participation in the study.
  • Patients who have not participated in any other clinical trial during the 3 months prior to the inclusion visit.
  • Patients who sign the informed consent.

Who cannot join

  • Patients who present SOME of the following criteria may not be selected to participate in this study:
  • CLI with tissue loss in the target member (category 6 of RB).
  • Previous major amputation in the target member.
  • Uncontrolled hypertension (defined as PAS> 180 or PAD> 110 in at least 2 determinations during the selection period).
  • Patients with severe heart failure or ejection fraction less than 30%.
  • Patients with a previous diagnosis of ventricular arrhythmias or unstable angina.
Show all 18Show fewer
  • Patients with septicemia.
  • Patients diagnosed with deep vein thrombosis in the 3 months prior to their inclusion in the study.
  • Concomitant therapy that includes hyperbaric oxygen, angiogenic agents or Cox II inhibitors.
  • Contraindication to perfusion NMR.
  • Proliferative retinopathy without treatment.
  • Diabetic nephropathy in hemodialysis.
  • Patients previously treated with cell therapy, gene therapy or growth factors in the last year.
  • Concomitant disease that limits life expectancy to 1 year or that does not ensure the follow-up period.
  • Patients who have suffered a stroke or myocardial infarction in the 3 months prior to the inclusion visit.
  • Severe anemia (hemoglobin <7.9g / dl) in the inclusion analysis.
  • Patients with a previous diagnosis of chronic alcoholism.
  • Any clinically significant anomaly detected in the Selection Period and which, in the opinion of the investigator, constitutes an impediment to the correct participation of the patient in the study or the fulfillment of the procedures established therein.

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

Spain10 sites

  • Hospital General de Alicante

    Alicante

  • Hospital Gregorio Marañon

    Madrid

  • Hospital Universitario Fundacion Jimenez Diaz

    Madrid

  • La Paz University Hospital

    Madrid

  • Hospital Clinico Universitario Virgen de la Arrixaca

    Murcia

  • Clinica Universidad de Navarra

    Pamplona

  • Hospital Universitario de Salamanca

    Salamanca

  • Hospital Victoria Eugenia Cruz Roja Española

    Seville

  • Hospital Universitario La Fe

    Valencia

  • Hospital de Valladolid

    Valladolid

Other trials in Spain

About this study

Official title: Multicenter, Randomized, Dose-search, Parallel, Double-blind, and Placebo-controlled Clinical Trial to Evaluate the Safety and Efficacy of Intramuscular Administration of Allogeneic Adipose Tissue Adult Mesenchymal Stem Cells in Diabetic Patients With Critical Limb Ischemia Without Possibility of Revascularization

Phase II national, multicenter, double-blind, randomized, placebo-controlled, phase-3 clinical trial of 3 parallel groups.

Read the detailed description

Disease or disorder under study: Critical ischemia of the lower limbs in diabetic patients without the possibility of revascularization.

Main valuation variable: Proportion of Adverse Events related to treatment.

Being tested
High dose allogeneic mesenchymal stromal cells, Low dose allogeneic mesenchymal stromal cells, Placebos
Medical subject headings
Diabetic Foot

What participants receive

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

  • High dose allogeneic mesenchymal stromal cellsDrug

    Allogeneic mesenchymal stromal cells derived from adipose tissue administered intramuscularly

  • Low dose allogeneic mesenchymal stromal cellsDrug

    Allogeneic mesenchymal stromal cells derived from adipose tissue administered intramuscularly

  • PlacebosDrug

    0,9% physiological saline

Study groups in NCT04466007
Study groupRoleWhat they receive
Control armPlacebo comparator0.9% physiological saline
Receives: Drug: Placebos
Low dose treatment armExperimentalLow dose allogeneic mesenchymal stem cells derived from adipose tissue
Receives: Drug: Low dose allogeneic mesenchymal stromal cells
High dose treatment armExperimentalHigh dose allogeneic mesenchymal stem cells derived from adipose tissue
Receives: Drug: High dose allogeneic mesenchymal stromal cells

What is being measured

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

  1. Complication rate after treatment administration

    Measured: 1 year

Secondary outcomes (8)

  1. Evaluation of vascularization though RMN

    Measured: 1 year

  2. Rutherford-Becker scale

    Measured: 1 year

  3. Wifi scale

    Measured: 1 year

  4. Ankle arm index

    Measured: 1 year

  5. Temperature

    (ºC)

    Measured: 1 year

  6. Twin perimeter

    (cm)

    Measured: 1 year

  7. Neuropathic symptoms (altered sensitivity)

    Measured: 1 year

  8. % amputations

    Measured: 1 year

Timeline

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

  1. First posted10 Jul 2020
  2. Study start11 Jan 2021
  3. Primary completion27 May 2024
  4. Study completion5 Dec 2024

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
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
90 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04466007
Sponsor's protocol ID
NOMA (No More Amputations)
Status last verified
Oct 2024
First submitted
1 Jul 2020
Last updated
27 Apr 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Garcia-Olmo D, Schwartz DA. Cumulative Evidence That Mesenchymal Stem Cells Promote Healing of Perianal Fistulas of Patients With Crohn's Disease--Going From Bench to Bedside. Gastroenterology. 2015 Oct;149(4):853-7. doi: 10.1053/j.gastro.2015.08.038. Epub 2015 Aug 24. No abstract available.

    PubMed 26311275

  • Garcia-Olmo D, Garcia-Arranz M, Herreros D, Pascual I, Peiro C, Rodriguez-Montes JA. A phase I clinical trial of the treatment of Crohn's fistula by adipose mesenchymal stem cell transplantation. Dis Colon Rectum. 2005 Jul;48(7):1416-23. doi: 10.1007/s10350-005-0052-6.

    PubMed 15933795

  • Garcia-Olmo D, Herreros D, Pascual I, Pascual JA, Del-Valle E, Zorrilla J, De-La-Quintana P, Garcia-Arranz M, Pascual M. Expanded adipose-derived stem cells for the treatment of complex perianal fistula: a phase II clinical trial. Dis Colon Rectum. 2009 Jan;52(1):79-86. doi: 10.1007/DCR.0b013e3181973487.

    PubMed 19273960

  • Panes J, Garcia-Olmo D, Van Assche G, Colombel JF, Reinisch W, Baumgart DC, Dignass A, Nachury M, Ferrante M, Kazemi-Shirazi L, Grimaud JC, de la Portilla F, Goldin E, Richard MP, Diez MC, Tagarro I, Leselbaum A, Danese S; ADMIRE CD Study Group Collaborators. Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease. Gastroenterology. 2018 Apr;154(5):1334-1342.e4. doi: 10.1053/j.gastro.2017.12.020. Epub 2017 Dec 24.

    PubMed 29277560

  • Panes J, Garcia-Olmo D, Van Assche G, Colombel JF, Reinisch W, Baumgart DC, Dignass A, Nachury M, Ferrante M, Kazemi-Shirazi L, Grimaud JC, de la Portilla F, Goldin E, Richard MP, Leselbaum A, Danese S; ADMIRE CD Study Group Collaborators. Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn's disease: a phase 3 randomised, double-blind controlled trial. Lancet. 2016 Sep 24;388(10051):1281-90. doi: 10.1016/S0140-6736(16)31203-X. Epub 2016 Jul 29.

    PubMed 27477896

  • Sanz-Baro R, Garcia-Arranz M, Guadalajara H, de la Quintana P, Herreros MD, Garcia-Olmo D. First-in-Human Case Study: Pregnancy in Women With Crohn's Perianal Fistula Treated With Adipose-Derived Stem Cells: A Safety Study. Stem Cells Transl Med. 2015 Jun;4(6):598-602. doi: 10.5966/sctm.2014-0255. Epub 2015 Apr 29.

    PubMed 25925838

  • 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

  • Gensler SW, Haimovici H, Hoffert P, Steinman C, Beneventano TC. Study of vascular lesions in diabetic, nondiabetic patients. Clinical, arteriographic, and surgical considerations. Arch Surg. 1965 Oct;91(4):617-22. doi: 10.1001/archsurg.1965.01320160071016. No abstract available.

    PubMed 5836112

  • Ciavarella A, Silletti A, Mustacchio A, Gargiulo M, Galaverni MC, Stella A, Vannini P. Angiographic evaluation of the anatomic pattern of arterial obstructions in diabetic patients with critical limb ischaemia. Diabete Metab. 1993 Nov-Dec;19(6):586-9.

    PubMed 8026611

  • Ouriel K. Peripheral arterial disease. Lancet. 2001 Oct 13;358(9289):1257-64. doi: 10.1016/S0140-6736(01)06351-6.

    PubMed 11675083

  • Meijer WT, Hoes AW, Rutgers D, Bots ML, Hofman A, Grobbee DE. Peripheral arterial disease in the elderly: The Rotterdam Study. Arterioscler Thromb Vasc Biol. 1998 Feb;18(2):185-92. doi: 10.1161/01.atv.18.2.185.

    PubMed 9484982

  • Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM Jr, White CJ, White J, White RA, Antman EM, Smith SC Jr, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B; American Association for Vascular Surgery; Society for Vascular Surgery; Society for Cardiovascular Angiography and Interventions; Society for Vascular Medicine and Biology; Society of Interventional Radiology; ACC/AHA Task Force on Practice Guidelines Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease; American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; Vascular Disease Foundation. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation. 2006 Mar 21;113(11):e463-654. doi: 10.1161/CIRCULATIONAHA.106.174526. No abstract available.

    PubMed 16549646

  • Saha SP, Whayne TF Jr, Mukherjee D. Current evidence for antithrombotic therapy after peripheral vascular interventions. Curr Vasc Pharmacol. 2013 Jul;11(4):507-13. doi: 10.2174/1570161111311040014.

    PubMed 22272907

  • Isner JM, Rosenfield K. Redefining the treatment of peripheral artery disease. Role of percutaneous revascularization. Circulation. 1993 Oct;88(4 Pt 1):1534-57. doi: 10.1161/01.cir.88.4.1534. No abstract available.

    PubMed 8403302

  • Andros G. Diagnostic and therapeutic arterial interventions in the ulcerated diabetic foot. Diabetes Metab Res Rev. 2004 May-Jun;20 Suppl 1:S29-33. doi: 10.1002/dmrr.468.

    PubMed 15150810

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing High dose allogeneic mesenchymal stromal cells and Low dose allogeneic mesenchymal stromal cells in people with Limb Ischemia and Diabetic Foot, run by Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz at 10 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 18 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 27 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 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. Some participants in this study may receive a placebo. 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?

Complication rate after treatment administration (time frame: 1 year). 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 NCT04466007, which also lists 51 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 27 Apr 2025.

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