Autologous Peripheral Blood Mononuclear Cells in Diabetic Foot Patients With No-option Critical Limb Ischemia
NCT ID: NCT04255004
Last Updated: 2020-02-05
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
Recruitment Status
COMPLETED
Clinical Phase
NA
Total Enrollment
76 participants
Study Classification
INTERVENTIONAL
Study Start Date
2014-01-31
Study Completion Date
2019-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
The objective of this trial is to determine whether PBMNCs in diabetic patients with critical, non revascularizable limb ischemia can prevent major amputation and affect mortality and healing.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Autologous Bone Marrow Derived Mononuclear Cells in Treating Diabetic Patients With Critical Limb Ischemia
NCT00872326
Peripheral Vascular Diseases
Diabetic Foot
COMPLETED
PHASE1/PHASE2
Safety and Efficacy of Autologous Bone Marrow Stem Cells for Lower Extremity Ischemia Treating
NCT01903044
Lower Extremity Ischemia
Leg Ulcer
Peripheral Vascular Disease
+2 more
UNKNOWN
PHASE1/PHASE2
Safety and Efficacy of Allogeneic Adipose Tissue Mesenchymal Stem Cells in Diabetic Patients With Critical Limb Ischemia
NCT04466007
Limb Ischemia
Diabetic Foot
COMPLETED
PHASE2
Monocentric Trial: Stem Cell Emergency Life Threatening Limbs Arteriopathy (SCELTA)
NCT02454231
Critical Limb Ischemia
COMPLETED
PHASE2/PHASE3
Autologous Endothelial Progenitor Cells (EPCs) From Peripheral Blood in the Treatment of Critical Limb Ischemia
NCT01595776
Critical Limb Ischemia
COMPLETED
PHASE1/PHASE2
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
This is an interventional study with historical control group carried out to assess as primary outcome major amputations, overall mortality, number of healed patients in group of patients who received repetitive intra-muscular implant of PBMNCs (3 times; 4-week interval) in comparison to a historical internal control group with a 1:1 case-control ratio. Secondary outcomes are TCPO2, healing time and rest pain.
No-option critical limb ischaemia is defined by evidence of no run-off pedal vessels, failure after several percutaneous intervention and no longer possible re-intervention, failure after infra-genicular bypass grafting, no-walking capacity with severe comorbidities unfit for surgical or endovascular procedures.
Inclusion criteria are: a) ulcers with inadequate perfusion, as indicated by a transcutaneous oxygen pressure value (TcpO2) \<30 mmHg; b) ulcers with grade I or II or III and stage C as defined by the Texas University Classification System or W1,2,3 - I 3 - FI 0,1 as defined by the WiFI Classification System c) not eligible for angioplasty or vascular surgery or following failed revascularization; d) possibility to save foot support.
Exclusion criteria are: a) lesion site above the tibial-tarsal joint; b) moderate or severe infection according by the WiFI classification system; c) NYHA class IV; d) Anemia (Hb\<8g/dl); e) coagulation disorder/thrombocytopenia (PLT\< 50,000 per microliter); f) active cancer/leukemia or lymphoma hematological disease.
Standard of care in both groups includes: diabetes control maximization by the diabetologist, comprehensive foot assessment by the nurse together with the diabetologist, including determination of vibration perception threshold, 10-g monofilament test and TcpO2 measurement, dressings, off-loading and systemic therapy according to the IWGDF guidelines .
Informed consent for participation in the study during the progress of the clinical trial is obtained from all subjects.
Concentration of PB-MNCs autologous cell therapy is produced by a filtration-based point-of-care device with the intended for use intra-operatively, from 120 mL of anticoagulated blood. All the procedures are performed in operatory room with anaesthesiologic support (propofol and/or peripheral block). Blood withdrawal (120 ml) is collected through a peripheral venous access, than loaded and gravity filtration is allowed in about 10 minutes. During filtration, MNCs are captured in the filter while plasma, platelets (PLTs) and red blood cells (RBCs) are not retained. After appropriate surgical debridement of the wound bed multiple perilesional and intramuscular injections of PBMNC cells suspension (0.2-0.3cc in boluses) are injected along the relevant axis below the knee, at intervals of 1-2 cm and to a mean depth of 1.5-2 cm, using a 21G needle. This procedure is repeated on each patient for three times, at intervals of 30-45 days from each other.
Foot-sparing surgery, the removal of all the unviable tissue and the reconstruction of the foot to allow a functional deambulation,is performed at the same time of the last implant in the patients with increased TcpO2 value above 30 mmHg. Between the implants, diabetologists together with nurses evaluated changing in pain, infection signs, wound size, demarcation of the necrosis, granulation tissue formation, perilesional tissue trophism and TcpO2 value to optimize standard of care. After the first treatment, a two years follow-up is registered, with evaluation at 1-3-6-12-18-24 months.
A baseline assessment is carried out, in order to estimate any differences among cases and controls before the treatment. Statistical evaluation includes non-parametric tests (Mann-Whitney U test for independent samples for continuous variables and Cochrane chi-square test for discrete variables), evaluation of Relative Risk (RR), Absolute Risk Reduction (ARR), Relative Risk Reduction (RRR) and Number Needed to Treat (NNT), multivariate survival analysis (Kaplan-Meier's survival analysis model).
No-option critical limb ischaemia is defined by evidence of no run-off pedal vessels, failure after several percutaneous intervention and no longer possible re-intervention, failure after infra-genicular bypass grafting, no-walking capacity with severe comorbidities unfit for surgical or endovascular procedures.
Inclusion criteria are: a) ulcers with inadequate perfusion, as indicated by a transcutaneous oxygen pressure value (TcpO2) \<30 mmHg; b) ulcers with grade I or II or III and stage C as defined by the Texas University Classification System or W1,2,3 - I 3 - FI 0,1 as defined by the WiFI Classification System c) not eligible for angioplasty or vascular surgery or following failed revascularization; d) possibility to save foot support.
Exclusion criteria are: a) lesion site above the tibial-tarsal joint; b) moderate or severe infection according by the WiFI classification system; c) NYHA class IV; d) Anemia (Hb\<8g/dl); e) coagulation disorder/thrombocytopenia (PLT\< 50,000 per microliter); f) active cancer/leukemia or lymphoma hematological disease.
Standard of care in both groups includes: diabetes control maximization by the diabetologist, comprehensive foot assessment by the nurse together with the diabetologist, including determination of vibration perception threshold, 10-g monofilament test and TcpO2 measurement, dressings, off-loading and systemic therapy according to the IWGDF guidelines .
Informed consent for participation in the study during the progress of the clinical trial is obtained from all subjects.
Concentration of PB-MNCs autologous cell therapy is produced by a filtration-based point-of-care device with the intended for use intra-operatively, from 120 mL of anticoagulated blood. All the procedures are performed in operatory room with anaesthesiologic support (propofol and/or peripheral block). Blood withdrawal (120 ml) is collected through a peripheral venous access, than loaded and gravity filtration is allowed in about 10 minutes. During filtration, MNCs are captured in the filter while plasma, platelets (PLTs) and red blood cells (RBCs) are not retained. After appropriate surgical debridement of the wound bed multiple perilesional and intramuscular injections of PBMNC cells suspension (0.2-0.3cc in boluses) are injected along the relevant axis below the knee, at intervals of 1-2 cm and to a mean depth of 1.5-2 cm, using a 21G needle. This procedure is repeated on each patient for three times, at intervals of 30-45 days from each other.
Foot-sparing surgery, the removal of all the unviable tissue and the reconstruction of the foot to allow a functional deambulation,is performed at the same time of the last implant in the patients with increased TcpO2 value above 30 mmHg. Between the implants, diabetologists together with nurses evaluated changing in pain, infection signs, wound size, demarcation of the necrosis, granulation tissue formation, perilesional tissue trophism and TcpO2 value to optimize standard of care. After the first treatment, a two years follow-up is registered, with evaluation at 1-3-6-12-18-24 months.
A baseline assessment is carried out, in order to estimate any differences among cases and controls before the treatment. Statistical evaluation includes non-parametric tests (Mann-Whitney U test for independent samples for continuous variables and Cochrane chi-square test for discrete variables), evaluation of Relative Risk (RR), Absolute Risk Reduction (ARR), Relative Risk Reduction (RRR) and Number Needed to Treat (NNT), multivariate survival analysis (Kaplan-Meier's survival analysis model).
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Critical Limb Ischemia
Diabetic Foot
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
Allocation Method
NON_RANDOMIZED
Intervention Model
SEQUENTIAL
We would enroll a cohort of 38 consecutive diabetic patients with CLI in charge at the Diabetic Foot Unit of the San Donato Hospital in Arezzo or referred from other Italian hospitals, who have no option for revascularization or are not further eligible for revascularization according to ESVS ESC 2017 criteria to undergo PB-MNC implantation. Furthermore, an historical control group, with a 1:1 case-control ratio, will be collected backwards from our records, when PBMNCs cellular therapy was not available in our center, with same no-option CLI diagnosis.
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
A-PBMNC therapy
Patients in A-PBMNC therapy are treated with wound bed multiple perilesional and intramuscular injections of PBMNC cells suspension (0.2-0.3cc in boluses). This procedure is repeated on each patient for three times, at intervals of 30-45 days from each other.
Group Type
ACTIVE_COMPARATOR
Pall Celeris System, point of care device for human cell therapy
Intervention Type
DEVICE
Concentration of PB-MNCs autologous cell therapy was produced by a filtration-based point-of-care device. All the procedures were performed in operatory room with anaesthesiologic support (propofol and/or peripheral block). Blood withdrawal (120 ml) was collected through a peripheral venous access. Blood was loaded, and gravity filtration was allowed to proceed until the upstream side of the filter had no remaining blood; filtration last about 10 minutes. During filtration, MNCs were captured in the filter while plasma, platelets (PLTs) and red blood cells (RBCs) were not retained. Immediately concentrate solution is injected in the perilesional area and intramuscular in the foot and the leg (0.2-0.3cc in boluses) below the knee, at intervals of 1-2 cm and to a mean depth of 1.5-2 cm, using a 21G needle. This procedure is repeated on each patient for three times, at intervals of 30-45 days from each other.
No A-PBMNC therapy
Patients in No A-PBMNC therapy receive only supportive treatment including wound care and pain killer drug.
Group Type
NO_INTERVENTION
No interventions assigned to this group
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Pall Celeris System, point of care device for human cell therapy
Concentration of PB-MNCs autologous cell therapy was produced by a filtration-based point-of-care device. All the procedures were performed in operatory room with anaesthesiologic support (propofol and/or peripheral block). Blood withdrawal (120 ml) was collected through a peripheral venous access. Blood was loaded, and gravity filtration was allowed to proceed until the upstream side of the filter had no remaining blood; filtration last about 10 minutes. During filtration, MNCs were captured in the filter while plasma, platelets (PLTs) and red blood cells (RBCs) were not retained. Immediately concentrate solution is injected in the perilesional area and intramuscular in the foot and the leg (0.2-0.3cc in boluses) below the knee, at intervals of 1-2 cm and to a mean depth of 1.5-2 cm, using a 21G needle. This procedure is repeated on each patient for three times, at intervals of 30-45 days from each other.
Intervention Type
DEVICE
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* ulcers with inadequate perfusion, as indicated by a transcutaneous oxygen pressure value (TcpO2) \<30 mmHg;
* ulcers with grade I or II or III and stage C as defined by the Texas University Classification System or W1,2,3 - I 3 - FI 0,1 as defined by the WiFI Classification System
* not eligible for angioplasty or vascular surgery or following failed revascularization;
* possibility to save foot support.
* ulcers with grade I or II or III and stage C as defined by the Texas University Classification System or W1,2,3 - I 3 - FI 0,1 as defined by the WiFI Classification System
* not eligible for angioplasty or vascular surgery or following failed revascularization;
* possibility to save foot support.
Exclusion Criteria
* lesion site above the tibial-tarsal joint;
* moderate or severe infection according by the WiFI classification system;
* NYHA class IV; d) Anemia (Hb\<8g/dl);
* coagulation disorder/thrombocytopenia (PLT\< 50,000 per microliter);
* active cancer/leukemia or lymphoma hematological disease.
* moderate or severe infection according by the WiFI classification system;
* NYHA class IV; d) Anemia (Hb\<8g/dl);
* coagulation disorder/thrombocytopenia (PLT\< 50,000 per microliter);
* active cancer/leukemia or lymphoma hematological disease.
Minimum Eligible Age
18 Years
Maximum Eligible Age
90 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Ospedale San Donato
OTHER
Sponsor Role
lead
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Alessia Scatena
Principal Investigator
Responsibility Role
PRINCIPAL_INVESTIGATOR
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Leonardo Ercolini, MD
Role: STUDY_CHAIR
Vascular Surgery Unit San Donato Hospital Arezzo
References
Explore related publications, articles, or registry entries linked to this study.
Abu Dabrh AM, Steffen MW, Undavalli C, Asi N, Wang Z, Elamin MB, Conte MS, Murad MH. The natural history of untreated severe or critical limb ischemia. J Vasc Surg. 2015 Dec;62(6):1642-51.e3. doi: 10.1016/j.jvs.2015.07.065. Epub 2015 Sep 26.
Reference Type
BACKGROUND
Golomb BA, Dang TT, Criqui MH. Peripheral arterial disease: morbidity and mortality implications. Circulation. 2006 Aug 15;114(7):688-99. doi: 10.1161/CIRCULATIONAHA.105.593442. No abstract available.
Reference Type
BACKGROUND
Rigato M, Monami M, Fadini GP. Autologous Cell Therapy for Peripheral Arterial Disease: Systematic Review and Meta-Analysis of Randomized, Nonrandomized, and Noncontrolled Studies. Circ Res. 2017 Apr 14;120(8):1326-1340. doi: 10.1161/CIRCRESAHA.116.309045. Epub 2017 Jan 17.
Reference Type
BACKGROUND
Fantin A, Vieira JM, Gestri G, Denti L, Schwarz Q, Prykhozhij S, Peri F, Wilson SW, Ruhrberg C. Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction. Blood. 2010 Aug 5;116(5):829-40. doi: 10.1182/blood-2009-12-257832. Epub 2010 Apr 19.
Reference Type
BACKGROUND
Baer C, Squadrito ML, Iruela-Arispe ML, De Palma M. Reciprocal interactions between endothelial cells and macrophages in angiogenic vascular niches. Exp Cell Res. 2013 Jul 1;319(11):1626-34. doi: 10.1016/j.yexcr.2013.03.026. Epub 2013 Mar 28.
Reference Type
BACKGROUND
Wynn TA, Vannella KM. Macrophages in Tissue Repair, Regeneration, and Fibrosis. Immunity. 2016 Mar 15;44(3):450-462. doi: 10.1016/j.immuni.2016.02.015.
Reference Type
BACKGROUND
Krzyszczyk P, Schloss R, Palmer A, Berthiaume F. The Role of Macrophages in Acute and Chronic Wound Healing and Interventions to Promote Pro-wound Healing Phenotypes. Front Physiol. 2018 May 1;9:419. doi: 10.3389/fphys.2018.00419. eCollection 2018.
Reference Type
BACKGROUND
Awad O, Dedkov EI, Jiao C, Bloomer S, Tomanek RJ, Schatteman GC. Differential healing activities of CD34+ and CD14+ endothelial cell progenitors. Arterioscler Thromb Vasc Biol. 2006 Apr;26(4):758-64. doi: 10.1161/01.ATV.0000203513.29227.6f. Epub 2006 Jan 12.
Reference Type
BACKGROUND
Jarajapu YP, Hazra S, Segal M, Li Calzi S, Jadhao C, Qian K, Mitter SK, Raizada MK, Boulton ME, Grant MB. Vasoreparative dysfunction of CD34+ cells in diabetic individuals involves hypoxic desensitization and impaired autocrine/paracrine mechanisms. PLoS One. 2014 Apr 8;9(4):e93965. doi: 10.1371/journal.pone.0093965. eCollection 2014.
Reference Type
BACKGROUND
Spaltro G, Straino S, Gambini E, Bassetti B, Persico L, Zoli S, Zanobini M, Capogrossi MC, Spirito R, Quarti C, Pompilio G. Characterization of the Pall Celeris system as a point-of-care device for therapeutic angiogenesis. Cytotherapy. 2015 Sep;17(9):1302-13. doi: 10.1016/j.jcyt.2015.04.006. Epub 2015 May 30.
Reference Type
BACKGROUND
Moriya J, Minamino T, Tateno K, Shimizu N, Kuwabara Y, Sato Y, Saito Y, Komuro I. Long-term outcome of therapeutic neovascularization using peripheral blood mononuclear cells for limb ischemia. Circ Cardiovasc Interv. 2009 Jun;2(3):245-54. doi: 10.1161/CIRCINTERVENTIONS.108.799361. Epub 2009 Mar 30.
Reference Type
BACKGROUND
Persiani F, Paolini A, Camilli D, Mascellari L, Platone A, Magenta A, Furgiuele S. Peripheral Blood Mononuclear Cells Therapy for Treatment of Lower Limb Ischemia in Diabetic Patients: A Single-Center Experience. Ann Vasc Surg. 2018 Nov;53:190-196. doi: 10.1016/j.avsg.2018.05.036. Epub 2018 Jul 25.
Reference Type
BACKGROUND
Armstrong DG, Lavery LA, Harkless LB. Validation of a diabetic wound classification system. The contribution of depth, infection, and ischemia to risk of amputation. Diabetes Care. 1998 May;21(5):855-9. doi: 10.2337/diacare.21.5.855.
Reference Type
BACKGROUND
Wagner FW Jr. The dysvascular foot: a system for diagnosis and treatment. Foot Ankle. 1981 Sep;2(2):64-122. doi: 10.1177/107110078100200202. No abstract available.
Reference Type
BACKGROUND
Lipsky BA, Aragon-Sanchez J, Diggle M, Embil J, Kono S, Lavery L, Senneville E, Urbancic-Rovan V, Van Asten S; International Working Group on the Diabetic Foot; Peters EJ. IWGDF guidance on the diagnosis and management of foot infections in persons with diabetes. Diabetes Metab Res Rev. 2016 Jan;32 Suppl 1:45-74. doi: 10.1002/dmrr.2699. No abstract available.
Reference Type
BACKGROUND
Breivik H, Borchgrevink PC, Allen SM, Rosseland LA, Romundstad L, Hals EK, Kvarstein G, Stubhaug A. Assessment of pain. Br J Anaesth. 2008 Jul;101(1):17-24. doi: 10.1093/bja/aen103. Epub 2008 May 16.
Reference Type
BACKGROUND
Meloni M, Giurato L, Izzo V, Stefanini M, Pampana E, Gandini R, Uccioli L. Long term outcomes of diabetic haemodialysis patients with critical limb ischemia and foot ulcer. Diabetes Res Clin Pract. 2016 Jun;116:117-22. doi: 10.1016/j.diabres.2016.04.030. Epub 2016 Apr 26.
Reference Type
BACKGROUND
Dubsky M, Jirkovska A, Bem R, Fejfarova V, Pagacova L, Nemcova A, Sixta B, Chlupac J, Peregrin JH, Sykova E, Jude EB. Comparison of the effect of stem cell therapy and percutaneous transluminal angioplasty on diabetic foot disease in patients with critical limb ischemia. Cytotherapy. 2014 Dec;16(12):1733-8. doi: 10.1016/j.jcyt.2014.08.010. Epub 2014 Oct 7.
Reference Type
BACKGROUND
Mustapha JA, Katzen BT, Neville RF, Lookstein RA, Zeller T, Miller LE, Jaff MR. Disease Burden and Clinical Outcomes Following Initial Diagnosis of Critical Limb Ischemia in the Medicare Population. JACC Cardiovasc Interv. 2018 May 28;11(10):1011-1012. doi: 10.1016/j.jcin.2017.12.012. No abstract available.
Reference Type
BACKGROUND
Klaphake S, de Leur K, Mulder PG, Ho GH, de Groot HG, Veen EJ, Verhagen HJ, van der Laan L. Mortality after major amputation in elderly patients with critical limb ischemia. Clin Interv Aging. 2017 Nov 22;12:1985-1992. doi: 10.2147/CIA.S137570. eCollection 2017.
Reference Type
BACKGROUND
Martini R, Andreozzi GM, Deri A, Cordova R, Zulian P, Scarpazza O, Nalin F. Amputation rate and mortality in elderly patients with critical limb ischemia not suitable for revascularization. Aging Clin Exp Res. 2012 Jun;24(3 Suppl):24-7.
Reference Type
BACKGROUND
Pannell M, Labuz D, Celik MO, Keye J, Batra A, Siegmund B, Machelska H. Adoptive transfer of M2 macrophages reduces neuropathic pain via opioid peptides. J Neuroinflammation. 2016 Oct 7;13(1):262. doi: 10.1186/s12974-016-0735-z.
Reference Type
BACKGROUND
Hasegawa T, Kosaki A, Shimizu K, Matsubara H, Mori Y, Masaki H, Toyoda N, Inoue-Shibata M, Nishikawa M, Iwasaka T. Amelioration of diabetic peripheral neuropathy by implantation of hematopoietic mononuclear cells in streptozotocin-induced diabetic rats. Exp Neurol. 2006 Jun;199(2):274-80. doi: 10.1016/j.expneurol.2005.11.001. Epub 2005 Dec 6.
Reference Type
BACKGROUND
Molavi B, Zafarghandi MR, Aminizadeh E, Hosseini SE, Mirzayi H, Arab L, Baharvand H, Aghdami N. Safety and Efficacy of Repeated Bone Marrow Mononuclear Cell Therapy in Patients with Critical Limb Ischemia in a Pilot Randomized Controlled Trial. Arch Iran Med. 2016 Jun;19(6):388-96.
Reference Type
BACKGROUND
Kang WC, Oh PC, Lee K, Ahn T, Byun K. Increasing injection frequency enhances the survival of injected bone marrow derived mesenchymal stem cells in a critical limb ischemia animal model. Korean J Physiol Pharmacol. 2016 Nov;20(6):657-667. doi: 10.4196/kjpp.2016.20.6.657. Epub 2016 Oct 28.
Reference Type
BACKGROUND
Fadini GP, Albiero M, Bonora BM, Avogaro A. Angiogenic Abnormalities in Diabetes Mellitus: Mechanistic and Clinical Aspects. J Clin Endocrinol Metab. 2019 Nov 1;104(11):5431-5444. doi: 10.1210/jc.2019-00980.
Reference Type
BACKGROUND
Cianfarani F, Toietta G, Di Rocco G, Cesareo E, Zambruno G, Odorisio T. Diabetes impairs adipose tissue-derived stem cell function and efficiency in promoting wound healing. Wound Repair Regen. 2013 Jul-Aug;21(4):545-53. doi: 10.1111/wrr.12051. Epub 2013 Apr 29.
Reference Type
BACKGROUND
Rennert RC, Sorkin M, Januszyk M, Duscher D, Kosaraju R, Chung MT, Lennon J, Radiya-Dixit A, Raghvendra S, Maan ZN, Hu MS, Rajadas J, Rodrigues M, Gurtner GC. Diabetes impairs the angiogenic potential of adipose-derived stem cells by selectively depleting cellular subpopulations. Stem Cell Res Ther. 2014 Jun 18;5(3):79. doi: 10.1186/scrt468.
Reference Type
BACKGROUND
Navarro A, Marin S, Riol N, Carbonell-Uberos F, Minana MD. Human adipose tissue-resident monocytes exhibit an endothelial-like phenotype and display angiogenic properties. Stem Cell Res Ther. 2014 Apr 14;5(2):50. doi: 10.1186/scrt438.
Reference Type
BACKGROUND
Kornicka K, Houston J, Marycz K. Dysfunction of Mesenchymal Stem Cells Isolated from Metabolic Syndrome and Type 2 Diabetic Patients as Result of Oxidative Stress and Autophagy may Limit Their Potential Therapeutic Use. Stem Cell Rev Rep. 2018 Jun;14(3):337-345. doi: 10.1007/s12015-018-9809-x.
Reference Type
BACKGROUND
Inoue O, Usui S, Takashima SI, Nomura A, Yamaguchi K, Takeda Y, Goten C, Hamaoka T, Ootsuji H, Murai H, Kaneko S, Takamura M. Diabetes impairs the angiogenic capacity of human adipose-derived stem cells by reducing the CD271+ subpopulation in adipose tissue. Biochem Biophys Res Commun. 2019 Sep 17;517(2):369-375. doi: 10.1016/j.bbrc.2019.07.081. Epub 2019 Jul 27.
Reference Type
BACKGROUND
Wang SK, Green LA, Motaganahalli RL, Wilson MG, Fajardo A, Murphy MP. Rationale and design of the MarrowStim PAD Kit for the Treatment of Critical Limb Ischemia in Subjects with Severe Peripheral Arterial Disease (MOBILE) trial investigating autologous bone marrow cell therapy for critical limb ischemia. J Vasc Surg. 2017 Jun;65(6):1850-1857.e2. doi: 10.1016/j.jvs.2017.01.054. Epub 2017 Apr 5.
Reference Type
BACKGROUND
Hao C, Shintani S, Shimizu Y, Kondo K, Ishii M, Wu H, Murohara T. Therapeutic angiogenesis by autologous adipose-derived regenerative cells: comparison with bone marrow mononuclear cells. Am J Physiol Heart Circ Physiol. 2014 Sep 15;307(6):H869-79. doi: 10.1152/ajpheart.00310.2014. Epub 2014 Jul 25.
Reference Type
BACKGROUND
Kondo K, Shintani S, Shibata R, Murakami H, Murakami R, Imaizumi M, Kitagawa Y, Murohara T. Implantation of adipose-derived regenerative cells enhances ischemia-induced angiogenesis. Arterioscler Thromb Vasc Biol. 2009 Jan;29(1):61-6. doi: 10.1161/ATVBAHA.108.166496. Epub 2008 Oct 30.
Reference Type
BACKGROUND
Bora P, Majumdar AS. Adipose tissue-derived stromal vascular fraction in regenerative medicine: a brief review on biology and translation. Stem Cell Res Ther. 2017 Jun 15;8(1):145. doi: 10.1186/s13287-017-0598-y.
Reference Type
BACKGROUND
Zollino I, Campioni D, Sibilla MG, Tessari M, Malagoni AM, Zamboni P. A phase II randomized clinical trial for the treatment of recalcitrant chronic leg ulcers using centrifuged adipose tissue containing progenitor cells. Cytotherapy. 2019 Feb;21(2):200-211. doi: 10.1016/j.jcyt.2018.10.012. Epub 2018 Dec 22.
Reference Type
BACKGROUND
Huang P, Li S, Han M, Xiao Z, Yang R, Han ZC. Autologous transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells improves critical limb ischemia in diabetes. Diabetes Care. 2005 Sep;28(9):2155-60. doi: 10.2337/diacare.28.9.2155.
Reference Type
BACKGROUND
Fadini GP, Albiero M, Vigili de Kreutzenberg S, Boscaro E, Cappellari R, Marescotti M, Poncina N, Agostini C, Avogaro A. Diabetes impairs stem cell and proangiogenic cell mobilization in humans. Diabetes Care. 2013 Apr;36(4):943-9. doi: 10.2337/dc12-1084. Epub 2012 Oct 30.
Reference Type
BACKGROUND
Dong Z, Pan T, Fang Y, Wei Z, Gu S, Fang G, Liu Y, Luo Y, Liu H, Zhang T, Hu M, Guo D, Xu X, Chen B, Jiang J, Yang J, Shi Z, Zhu T, Shi Y, Liu P, Fu W. Purified CD34+ cells versus peripheral blood mononuclear cells in the treatment of angiitis-induced no-option critical limb ischaemia: 12-Month results of a prospective randomised single-blinded non-inferiority trial. EBioMedicine. 2018 Sep;35:46-57. doi: 10.1016/j.ebiom.2018.08.038. Epub 2018 Aug 29.
Reference Type
BACKGROUND
Fowkes FG, Rudan D, Rudan I, Aboyans V, Denenberg JO, McDermott MM, Norman PE, Sampson UK, Williams LJ, Mensah GA, Criqui MH. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet. 2013 Oct 19;382(9901):1329-40. doi: 10.1016/S0140-6736(13)61249-0. Epub 2013 Aug 1.
Reference Type
RESULT
Reinecke H, Unrath M, Freisinger E, Bunzemeier H, Meyborg M, Luders F, Gebauer K, Roeder N, Berger K, Malyar NM. Peripheral arterial disease and critical limb ischaemia: still poor outcomes and lack of guideline adherence. Eur Heart J. 2015 Apr 14;36(15):932-8. doi: 10.1093/eurheartj/ehv006. Epub 2015 Feb 2.
Reference Type
RESULT
Vas PRJ, Edmonds M, Kavarthapu V, Rashid H, Ahluwalia R, Pankhurst C, Papanas N. The Diabetic Foot Attack: "'Tis Too Late to Retreat!". Int J Low Extrem Wounds. 2018 Mar;17(1):7-13. doi: 10.1177/1534734618755582. Epub 2018 Feb 12.
Reference Type
RESULT
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
MONODIAB-19-01
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.
Autologous Bone Marrow-derived Mononuclear Cells for Therapeutic Arteriogenesis in Patients With Limb Ischemia
NCT00539266
UNKNOWN
PHASE2/PHASE3
Treatment of Chronic Critical Limb Ischemia With G-CSF-mobilized Autologous Peripheral Blood Mononuclear Cells
NCT01833585
COMPLETED
PHASE3
Safety and Efficacy of Autologous Bone Marrow Mononuclear Cells in Patients With Severe Critical Limb Ischemia
NCT01472289
COMPLETED
PHASE1/PHASE2
Autologous Stem Cells for the Treatment of No Option Critical Limb Ischemia
NCT03455335
COMPLETED
PHASE1
Intraarterial Infusion of Autologous Bone Marrow in Diabetic Patients With Chronic Ischemia of Lower Limbs (CLI) no Revascularization
NCT00987363
COMPLETED
PHASE1/PHASE2
Cell Therapy in Chronic Limb Ischemia
NCT00533104
COMPLETED
PHASE1/PHASE2
Autologous Bone Marrow Mononuclear Cells Therapy in Diabetic Lower Limb Ischemia
NCT01937416
UNKNOWN
PHASE1
Bone Marrow Mononuclear Cells vs Mesenchymal Stem Cells in Diabetic Patients With Chronic Limb Ischemia
NCT05631444
COMPLETED
PHASE1/PHASE2
Treatment of Severe Limb Ischemia With Autologous Bonemarrow Derived Mononuclear Cells
NCT00442143
UNKNOWN
PHASE1
Autologous Bone Marrow Stem Cell Transfer in Patients With Chronical Critical Limb Ischemia and Diabetic Foot
NCT01232673
COMPLETED
PHASE2
Cell Therapy With Bone Marrow Mononuclear Cells in Critical Leg Ischemia (CLI)
NCT00377897
UNKNOWN
PHASE1
Tolerability and Efficacy of Intravenous Infusion of Autologous MSC_Apceth for the Treatment of Critical Limb Ischemia
NCT01351610
COMPLETED
PHASE1/PHASE2
Autologous Bone Marrow Cell Treatment in Peripheral Atherosclerosis
NCT00306085
UNKNOWN
PHASE1
A Clinical Trial on Diabetic Foot Using Peripheral Blood Derived Stem Cells for Treating Critical Limb Ischemia
NCT00922389
UNKNOWN
PHASE1/PHASE2
Administration of Adipose-derived Stem Cells (ASC) in Patient With Critical Limb Ischemia.
NCT03968198
TERMINATED
PHASE2
Comparison of Autologous Mesenchymal Stem Cells and Mononuclear Cells on Diabetic Critical Limb Ischemia and Foot Ulcer
NCT00955669
COMPLETED
PHASE1
Outcomes of Expanded Autologous Bone Marrow-derived Mesenchymal Stem Cells Therapy in Type II Diabetes
NCT03343782
COMPLETED
PHASE1/PHASE2
Autologous BMMNC Combined With HA Therapy for PAOD
NCT03214887
WITHDRAWN
PHASE1/PHASE2
Intra-arterial Infusion of Autologous Bone Marrow Mononuclear Cells in Non-diabetic Patients With Critical Limb Ischemia (CLI).
NCT01408381
COMPLETED
PHASE2
Purified CD34+ Cells Versus Peripheral Blood Mononuclear Cells in Treatment of Critical Limb Ischemia
NCT02089828
UNKNOWN
NA
Critical Limb Ischemia Rapid Delivery by SurgWerks-CLI Kit and VXP System
NCT02538978
UNKNOWN
PHASE3
Intra-arterial Stem Cell Therapy for Patients With Chronic Limb Ischemia (CLI)
NCT00371371
COMPLETED
PHASE1/PHASE2
Safety and Efficacy Study of Autologous Bone Marrow Aspirate Concentrate for No-Option Critical Limb Ischemia
NCT01818310
COMPLETED
PHASE2/PHASE3
Cell Therapy With Mesenchymal Stem Cell in Ischemic Limb Disease
NCT02336646
COMPLETED
PHASE1
Hematopoietic Stem Cell Transplantation for the Treatment of Limb Ischemia and Diabetic Neuropathy
NCT00730561
COMPLETED
NA