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

December 12, 2012 updated by: R.W. Sprengers, MD, PhD, UMC Utrecht

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

160

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Utrecht, Netherlands, 3508 GA
        • University Medical Center Utrecht (UMC Utrecht)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Procedure: Bone marrow punction
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.
Procedure: Placebo infusion
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.
Experimental: BM-MNC
autologous bone marrow-derived mononuclear cells
Procedure: Bone marrow punction
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.
Procedure: BM-MNC infusion
Repeated intra-arterial infusion of autologous BM-MNC into the common femoral artery

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
major amputation
Time Frame: six months
six months

Secondary Outcome Measures

Outcome Measure
Time Frame
minor amputation
Time Frame: six months
six months
number and extent of leg ulcers
Time Frame: six months
six months
resolvement of rest pain
Time Frame: six months
six months
improvement of ankle-brachial index (ABI)
Time Frame: six months
six months
improvement transcutaneous oxygen pressure (TcpO2)
Time Frame: six months
six months
changes in quality of life
Time Frame: suix months
suix months
changes in clinical status (Rutherford classification)
Time Frame: six months
six months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Amputation-free survival
Time Frame: six months
six months
Treatment failure
Time Frame: six months
Composite endpoint defined as major amputation of treated leg, all-cause mortality, doubling in total wound surface area, or de novo gangrene
six months
Successfull treatment
Time Frame: six months
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UMC Utrecht

Collaborators

Catharijne Foundation

Investigators

  • Study Chair: Frans L Moll, MD, PhD, UMC Utrecht
  • Study Director: Marianne C Verhaar, MD, PhD, UMC Utrecht
  • Principal Investigator: Ralf W Sprengers, MD, PhD, UMC Utrecht
  • Principal Investigator: Martin Teraa, MD, UMC Utrecht

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2006

Primary Completion (Actual)

December 1, 2012

Study Completion (Actual)

December 1, 2012

Study Registration Dates

First Submitted

September 1, 2006

First Submitted That Met QC Criteria

September 1, 2006

First Posted (Estimate)

September 4, 2006

Study Record Updates

Last Update Posted (Estimate)

December 13, 2012

Last Update Submitted That Met QC Criteria

December 12, 2012

Last Verified

December 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • JUVENTAS
  • 06/030 (Other Grant/Funding Number: Catharijne Foundation)
  • CS 06.007

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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