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| ID | Type | Description | Link |
|---|---|---|---|
| 06/030 | Other Grant/Funding Number | Catharijne Foundation | |
| CS 06.007 |
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| Name | Class |
|---|---|
| Catharijne Foundation | UNKNOWN |
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The purposes of this study are to determine whether intra-arterial injection of autologous stem cells is effective in the treatment of chronic limb ischemia (CLI), to characterize stem cell dysfunction in patients with CLI, and to relate the stem cell function with clinical outcome.
Despite advances in surgical and radiological vascular techniques, a significant number of patients with chronic critical limb ischaemia (CLI) are not eligible for revascularization procedures, often leaving amputation as the only option. Consequently, exploring new strategies for revascularization of ischemic limbs is of major importance. Preclinical studies and pioneering clinical trials suggest that administration of bone marrow (BM) mononuclear cells (MNC) into ischemic limbs enhances neovascularization, improves tissue perfusion and prevents amputation. However, no definite proof is available as the clinical studies thus far have been small and lacked double-blinded controls.
JUVENTAS is a randomized, double-blinded placebo-controlled trial in 109 - 160 patients with CLI to investigate the potential clinical effects of repeated intra-arterial infusion of BM-MNC in these patients (the exact number of patients to be included cannot be specified in advance because of the planned group sequential interim analyses). In addition, it will study the functional characteristics of the BM-MNC obtained from CLI patients and relate BM-MNC dysfunction to clinical outcome.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BM-MNC | Experimental | autologous bone marrow-derived mononuclear cells |
|
| Placebo | Placebo Comparator | Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bone marrow punction | Procedure | A total volume of 100 ml bone marrow will be aspirated from the iliac crest under local anaesthesia (lidocaine) according to local routine. To maximise the patients comfort, 5-10 mg midazolam and 50 ug fentanyl will be administered intravenously. |
| Measure | Description | Time Frame |
|---|---|---|
| major amputation | six months |
| Measure | Description | Time Frame |
|---|---|---|
| minor amputation | six months | |
| number and extent of leg ulcers | six months | |
| resolvement of rest pain |
| Measure | Description | Time Frame |
|---|---|---|
| Amputation-free survival | six months | |
| Treatment failure | Composite endpoint defined as major amputation of treated leg, all-cause mortality, doubling in total wound surface area, or de novo gangrene | six months |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Frans L Moll, MD, PhD | UMC Utrecht | Study Chair |
| Marianne C Verhaar, MD, PhD | UMC Utrecht | Study Director |
| Ralf W Sprengers, MD, PhD | UMC Utrecht | Principal Investigator |
| Martin Teraa, MD | UMC Utrecht | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Medical Center Utrecht (UMC Utrecht) | Utrecht | 3508 GA | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18376183 | Background | Sprengers RW, Lips DJ, Moll FL, Verhaar MC. Progenitor cell therapy in patients with critical limb ischemia without surgical options. Ann Surg. 2008 Mar;247(3):411-20. doi: 10.1097/SLA.0b013e318153fdcb. | |
| 19837547 | Background | Sprengers RW, Janssen KJ, Moll FL, Verhaar MC, van der Graaf Y; SMART Study Group. Prediction rule for cardiovascular events and mortality in peripheral arterial disease patients: data from the prospective Second Manifestations of ARTerial disease (SMART) cohort study. J Vasc Surg. 2009 Dec;50(6):1369-76. doi: 10.1016/j.jvs.2009.07.095. Epub 2009 Oct 17. |
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| ID | Term |
|---|---|
| D016491 | Peripheral Vascular Diseases |
| D001157 | Arterial Occlusive Diseases |
| D007871 | Leg Ulcer |
| D005734 | Gangrene |
| D007511 | Ischemia |
| D000089802 | Chronic Limb-Threatening Ischemia |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D012883 | Skin Ulcer |
| D012871 | Skin Diseases |
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|
| BM-MNC infusion | Procedure | Repeated intra-arterial infusion of autologous BM-MNC into the common femoral artery |
|
| Placebo infusion | Procedure | Repeated intra-arterial infusion of placebo (PBS/4% HAS/heparin, coloured with autologous erythrocytes to match the colour of BM-MNC suspension) into the common femoral artery. |
|
| six months |
| improvement of ankle-brachial index (ABI) | six months |
| improvement transcutaneous oxygen pressure (TcpO2) | six months |
| changes in quality of life | suix months |
| changes in clinical status (Rutherford classification) | six months |
| Successfull treatment | Composite endpoint defined as subject is (A) alive, (B) without major amputation of index limb, (C) not worsened rutherford class or VAS, and (D) improved in either Rutherford or VAS (>30mm) | six months |
| 20153223 | Background | Sprengers RW, Moll FL, Verhaar MC. Stem cell therapy in PAD. Eur J Vasc Endovasc Surg. 2010 Mar;39 Suppl 1:S38-43. doi: 10.1016/j.ejvs.2009.12.001. Epub 2010 Feb 12. |
| 20488328 | Background | Sprengers RW, Moll FL, Teraa M, Verhaar MC; JUVENTAS Study Group. Rationale and design of the JUVENTAS trial for repeated intra-arterial infusion of autologous bone marrow-derived mononuclear cells in patients with critical limb ischemia. J Vasc Surg. 2010 Jun;51(6):1564-8. doi: 10.1016/j.jvs.2010.02.020. |
| 20598482 | Background | Sprengers RW, Teraa M, Moll FL, de Wit GA, van der Graaf Y, Verhaar MC; JUVENTAS Study Group; SMART Study Group. Quality of life in patients with no-option critical limb ischemia underlines the need for new effective treatment. J Vasc Surg. 2010 Oct;52(4):843-9, 849.e1. doi: 10.1016/j.jvs.2010.04.057. |
| 35802393 | Derived | Moazzami B, Mohammadpour Z, Zabala ZE, Farokhi E, Roohi A, Dolmatova E, Moazzami K. Local intramuscular transplantation of autologous bone marrow mononuclear cells for critical lower limb ischaemia. Cochrane Database Syst Rev. 2022 Jul 8;7(7):CD008347. doi: 10.1002/14651858.CD008347.pub4. |
| 33144352 | Derived | Hanssen NMJ, Teraa M, Scheijen JLJM, Van de Waarenburg M, Gremmels H, Stehouwer CDA, Verhaar MC, Schalkwijk CG. Plasma Methylglyoxal Levels Are Associated With Amputations and Mortality in Severe Limb Ischemia Patients With and Without Diabetes. Diabetes Care. 2021 Jan;44(1):157-163. doi: 10.2337/dc20-0581. Epub 2020 Nov 3. |
| 26428987 | Derived | Teraa M, Schutgens RE, Sprengers RW, Slaper-Cortenbach I, Moll FL, Verhaar MC; Juventas Study Group. Core diameter of bone marrow aspiration devices influences cell density of bone marrow aspirate in patients with severe peripheral artery disease. Cytotherapy. 2015 Dec;17(12):1807-12. doi: 10.1016/j.jcyt.2015.08.004. Epub 2015 Sep 28. |
| 26148006 | Derived | Wisman PP, Teraa M, de Borst GJ, Verhaar MC, Roest M, Moll FL. Baseline Platelet Activation and Reactivity in Patients with Critical Limb Ischemia. PLoS One. 2015 Jul 6;10(7):e0131356. doi: 10.1371/journal.pone.0131356. eCollection 2015. |
| 25567765 | Derived | Teraa M, Sprengers RW, Schutgens RE, Slaper-Cortenbach IC, van der Graaf Y, Algra A, van der Tweel I, Doevendans PA, Mali WP, Moll FL, Verhaar MC. Effect of repetitive intra-arterial infusion of bone marrow mononuclear cells in patients with no-option limb ischemia: the randomized, double-blind, placebo-controlled Rejuvenating Endothelial Progenitor Cells via Transcutaneous Intra-arterial Supplementation (JUVENTAS) trial. Circulation. 2015 Mar 10;131(10):851-60. doi: 10.1161/CIRCULATIONAHA.114.012913. Epub 2015 Jan 7. |
| 24218170 | Derived | Teraa M, Fledderus JO, Rozbeh RI, Leguit RJ, Verhaar MC; Juventas Study Groupdagger. Bone marrow microvascular and neuropathic alterations in patients with critical limb ischemia. Circ Res. 2014 Jan 17;114(2):311-4. doi: 10.1161/CIRCRESAHA.114.302791. Epub 2013 Nov 11. |
| D017437 |
| Skin and Connective Tissue Diseases |
| D009336 | Necrosis |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D058729 | Peripheral Arterial Disease |
| D050197 | Atherosclerosis |
| D001161 | Arteriosclerosis |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |