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Trial record 21 of 34 for:    stem cell peripheral arterial disease AND marrow

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00371371
Recruitment Status : Completed
First Posted : September 4, 2006
Last Update Posted : December 13, 2012
Catharijne Foundation
Information provided by (Responsible Party):
R.W. Sprengers, MD, PhD, UMC Utrecht

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.

Condition or disease Intervention/treatment 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

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : September 2006
Actual Primary Completion Date : December 2012
Actual Study Completion Date : December 2012

Arm Intervention/treatment
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
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.

Primary Outcome Measures :
  1. major amputation [ Time Frame: six months ]

Secondary Outcome Measures :
  1. minor amputation [ Time Frame: six months ]
  2. number and extent of leg ulcers [ Time Frame: six months ]
  3. resolvement of rest pain [ Time Frame: six months ]
  4. improvement of ankle-brachial index (ABI) [ Time Frame: six months ]
  5. improvement transcutaneous oxygen pressure (TcpO2) [ Time Frame: six months ]
  6. changes in quality of life [ Time Frame: suix months ]
  7. changes in clinical status (Rutherford classification) [ Time Frame: six months ]

Other Outcome Measures:
  1. Amputation-free survival [ Time Frame: six months ]
  2. 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

  3. 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)

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00371371

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University Medical Center Utrecht (UMC Utrecht)
Utrecht, Netherlands, 3508 GA
Sponsors and Collaborators
UMC Utrecht
Catharijne Foundation
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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 automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: R.W. Sprengers, MD, PhD, Investigator, UMC Utrecht Identifier: NCT00371371    
Other Study ID Numbers: JUVENTAS
06/030 ( Other Grant/Funding Number: Catharijne Foundation )
CS 06.007
First Posted: September 4, 2006    Key Record Dates
Last Update Posted: December 13, 2012
Last Verified: December 2012
Keywords provided by R.W. Sprengers, MD, PhD, UMC Utrecht:
clinical trial
chronic critical limb ischemia
leg pain
cell therapy
bone marrow
progenitor cell
stem cell
critical limb ischemia
nonhealing leg ulcer
Additional relevant MeSH terms:
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Vascular Diseases
Peripheral Vascular Diseases
Peripheral Arterial Disease
Arterial Occlusive Diseases
Pathologic Processes
Cardiovascular Diseases
Skin Diseases
Leg Ulcer
Skin Ulcer