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

This study has been completed.
Sponsor:
Collaborator:
Catharijne Foundation
Information provided by (Responsible Party):
R.W. Sprengers, MD, PhD, UMC Utrecht
ClinicalTrials.gov Identifier:
NCT00371371
First received: September 1, 2006
Last updated: December 12, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Peripheral Vascular Diseases
Arterial Occlusive Diseases
Leg Ulcer
Gangrene
Ischemia
Procedure: Bone marrow punction
Procedure: BM-MNC infusion
Procedure: Placebo infusion
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Intra-arterial Infusion of Autologous Bone Marrow Mononuclear Cells in Patients With Chronic Critical Limb Ischemia: a Randomized, Placebo-controlled Clinical Trial

Resource links provided by NLM:


Further study details as provided by UMC Utrecht:

Primary Outcome Measures:
  • major amputation [ Time Frame: six months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • minor amputation [ Time Frame: six months ] [ Designated as safety issue: Yes ]
  • number and extent of leg ulcers [ Time Frame: six months ] [ Designated as safety issue: No ]
  • resolvement of rest pain [ Time Frame: six months ] [ Designated as safety issue: No ]
  • improvement of ankle-brachial index (ABI) [ Time Frame: six months ] [ Designated as safety issue: No ]
  • improvement transcutaneous oxygen pressure (TcpO2) [ Time Frame: six months ] [ Designated as safety issue: No ]
  • changes in quality of life [ Time Frame: suix months ] [ Designated as safety issue: No ]
  • changes in clinical status (Rutherford classification) [ Time Frame: six months ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Amputation-free survival [ Time Frame: six months ] [ Designated as safety issue: No ]
  • Treatment failure [ Time Frame: six months ] [ Designated as safety issue: No ]
    Composite endpoint defined as major amputation of treated leg, all-cause mortality, doubling in total wound surface area, or de novo gangrene

  • Successfull treatment [ Time Frame: six months ] [ Designated as safety issue: No ]
    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)


Enrollment: 160
Study Start Date: September 2006
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Placebo Comparator: Placebo
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00371371

Locations
Netherlands
University Medical Center Utrecht (UMC Utrecht)
Utrecht, Netherlands, 3508 GA
Sponsors and Collaborators
UMC Utrecht
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
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: R.W. Sprengers, MD, PhD, Investigator, UMC Utrecht
ClinicalTrials.gov Identifier: NCT00371371     History of Changes
Other Study ID Numbers: JUVENTAS, 06/030, CS 06.007
Study First Received: September 1, 2006
Last Updated: December 12, 2012
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by UMC Utrecht:
clinical trial
chronic critical limb ischemia
leg pain
cell therapy
bone marrow
mononuclear
progenitor cell
stem cell
critical limb ischemia
nonhealing leg ulcer

Additional relevant MeSH terms:
Arterial Occlusive Diseases
Gangrene
Ischemia
Leg Ulcer
Ulcer
Vascular Diseases
Peripheral Vascular Diseases
Peripheral Arterial Disease
Cardiovascular Diseases
Necrosis
Pathologic Processes
Skin Ulcer
Skin Diseases
Atherosclerosis
Arteriosclerosis

ClinicalTrials.gov processed this record on August 18, 2014