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Peripheral Vascular DiseasesPhase 1/2JUVENTASNCT00371371

Intra-arterial Stem Cell Therapy for Patients With Chronic Limb Ischemia (CLI)

A Phase 1/2 study testing Bone marrow punction and BM-MNC infusion in people with Peripheral Vascular Diseases and Arterial Occlusive Diseases, run by UMC Utrecht at 1 site in Netherlands.

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 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Bone marrow punction and BM-MNC infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
160 participants
Where
1 siteNetherlands
Study dates
Sep 2006to Dec 2012
Phase
Phase 1/2
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • University Medical Center Utrecht (UMC Utrecht)

    Utrecht, 3508 GA

Other trials in Netherlands

About this study

Official title: Intra-arterial Infusion of Autologous Bone Marrow Mononuclear Cells in Patients With Chronic Critical Limb Ischemia: a Randomized, Placebo-controlled Clinical Trial

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.

Read the detailed description

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.

Being tested
Bone marrow punction, BM-MNC infusion, Placebo infusion
Keywords
clinical trial, chronic critical limb ischemia, leg pain, cell therapy, bone marrow, mononuclear, progenitor cell, stem cell, critical limb ischemia, nonhealing leg ulcer
Medical subject headings
Peripheral Vascular Diseases, Arterial Occlusive Diseases, Leg Ulcer, Gangrene, Ischemia, Chronic Limb-Threatening Ischemia

What participants receive

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

  • Bone marrow punctionProcedure or surgery

    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-MNC infusionProcedure or surgery

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

  • Placebo infusionProcedure or surgery

    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.

Study groups in NCT00371371
Study groupRoleWhat they receive
BM-MNCExperimentalautologous bone marrow-derived mononuclear cells
Receives: Procedure: Bone marrow punction; Procedure: BM-MNC infusion
PlaceboPlacebo comparatorPlacebo
Receives: Procedure: Bone marrow punction; Procedure: Placebo infusion

What is being measured

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

  1. major amputation

    Measured: six months

Secondary outcomes (7)

  1. minor amputation

    Measured: six months

  2. number and extent of leg ulcers

    Measured: six months

  3. resolvement of rest pain

    Measured: six months

  4. improvement of ankle-brachial index (ABI)

    Measured: six months

  5. improvement transcutaneous oxygen pressure (TcpO2)

    Measured: six months

  6. changes in quality of life

    Measured: suix months

  7. changes in clinical status (Rutherford classification)

    Measured: six months

Timeline

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

  1. First posted4 Sep 2006 (estimated)
  2. Study startSep 2006
  3. Primary completionDec 2012
  4. Study completionDec 2012

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
160 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00371371
Sponsor's protocol ID
JUVENTAS
Other IDs
06/030, CS 06.007
Acronym
JUVENTAS
Status last verified
Dec 2012
First submitted
1 Sep 2006
Last updated
13 Dec 2012
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 18376183

  • 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.

    PubMed 19837547

  • 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.

    PubMed 20153223

  • 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.

    PubMed 20488328

  • 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.

    PubMed 20598482

  • 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.

    PubMed 35802393

  • 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.

    PubMed 33144352

  • 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.

    PubMed 26428987

  • 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.

    PubMed 26148006

  • 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.

    PubMed 25567765

  • 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.

    PubMed 24218170

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Bone marrow punction and BM-MNC infusion in people with Peripheral Vascular Diseases and Arterial Occlusive Diseases, run by UMC Utrecht at 1 site in Netherlands.

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 6 inclusion and 5 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 13 Dec 2012. 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 Netherlands. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

major amputation (time frame: six months). 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 NCT00371371, which also lists 11 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 13 Dec 2012.

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