NCT00371371

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
160

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Sep 2006

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 1, 2006

Completed
Same day until next milestone

Study Start

First participant enrolled

September 1, 2006

Completed
3 days until next milestone

First Posted

Study publicly available on registry

September 4, 2006

Completed
6.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2012

Completed
Last Updated

December 13, 2012

Status Verified

December 1, 2012

Enrollment Period

6.3 years

First QC Date

September 1, 2006

Last Update Submit

December 12, 2012

Conditions

Peripheral Vascular DiseasesArterial Occlusive DiseasesLeg UlcerGangreneIschemia

Keywords

clinical trialchronic critical limb ischemialeg paincell therapybone marrowmononuclearprogenitor cellstem cellcritical limb ischemianonhealing leg ulcer

Outcome Measures

Primary Outcomes (1)

  • major amputation

    six months

Secondary Outcomes (7)

  • minor amputation

    six months

  • number and extent of leg ulcers

    six months

  • resolvement of rest pain

    six months

  • improvement of ankle-brachial index (ABI)

    six months

  • improvement transcutaneous oxygen pressure (TcpO2)

    six months

  • +2 more secondary outcomes

Other Outcomes (3)

  • Amputation-free survival

    six months

  • Treatment failure

    six months

  • Successfull treatment

    six months

Study Arms (2)

BM-MNC

EXPERIMENTAL

autologous bone marrow-derived mononuclear cells

Procedure: Bone marrow punctionProcedure: BM-MNC infusion

Placebo

PLACEBO COMPARATOR

Placebo

Procedure: Bone marrow punctionProcedure: Placebo infusion

Interventions

Bone marrow punctionPROCEDURE

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.

BM-MNCPlacebo
BM-MNC infusionPROCEDURE

Repeated intra-arterial infusion of autologous BM-MNC into the common femoral artery

BM-MNC
Placebo infusionPROCEDURE

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.

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age \> 18 years
  • Severe infra-popliteal peripheral arterial occlusive disease \[PAOD\] (Fontaine class IIb, III or IV)
  • Invalidating intermittent claudication, persistent, recurring rest pain requiring analgesia and/or non-healing ulcers present for \> 4 weeks without evidence of improvement in response to conventional therapies
  • Ankle brachial index \< 0.6 or "unreliable"
  • Not eligible for surgical or radiological revascularization
  • Written informed consent

You may not qualify if:

  • History of neoplasm or malignancy in the past 10 years
  • Serious known concomitant disease with life expectancy of less than one year
  • Anticipated inability to obtain 100 ml of bone marrow aspirate
  • Known infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C virus
  • Follow-up impossible

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Medical Center Utrecht (UMC Utrecht)

Utrecht, 3508 GA, Netherlands

Location

Related Publications (11)

  • 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.

    PMID: 18376183BACKGROUND

  • 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.

    PMID: 19837547BACKGROUND

  • 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.

    PMID: 20153223BACKGROUND

  • 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.

    PMID: 20488328BACKGROUND

  • 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.

    PMID: 20598482BACKGROUND

  • 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.

    PMID: 35802393DERIVED

  • 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.

    PMID: 33144352DERIVED

  • 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.

    PMID: 26428987DERIVED

  • 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.

    PMID: 26148006DERIVED

  • 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.

    PMID: 25567765DERIVED

  • 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.

    PMID: 24218170DERIVED

MeSH Terms

Conditions

Peripheral Vascular DiseasesArterial Occlusive DiseasesLeg UlcerGangreneIschemiaChronic Limb-Threatening Ischemia

Condition Hierarchy (Ancestors)

Vascular DiseasesCardiovascular DiseasesSkin UlcerSkin DiseasesSkin and Connective Tissue DiseasesNecrosisPathologic ProcessesPathological Conditions, Signs and SymptomsPeripheral Arterial DiseaseAtherosclerosisArteriosclerosisChronic DiseaseDisease Attributes

Study Officials

  • 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

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Investigator

Study Record Dates

First Submitted

September 1, 2006

First Posted

September 4, 2006

Study Start

September 1, 2006

Primary Completion

December 1, 2012

Study Completion

December 1, 2012

Last Updated

December 13, 2012

Record last verified: 2012-12

Locations

NL(1)