Intra-Arterial Stem Cell Therapy for Patients With Chronic Limb Ischemia (CLI) - Full Text View

Sponsors and Collaborators:	UMC Utrecht Catharijne Stichting
Information provided by:	UMC Utrecht
ClinicalTrials.gov Identifier:	NCT00371371

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 I Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy 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

Resource links provided by NLM:

MedlinePlus related topics: Leg Injuries and Disorders Peripheral Arterial Disease Vascular Diseases

U.S. FDA Resources

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 ]

Estimated Enrollment:	110
Study Start Date:	September 2006
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
BM-MNC: Experimental 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: 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.

Arms

Assigned Interventions

BM-MNC: Experimental

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: 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.

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 "non-compressible"
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

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

Contacts

Contact: Ralf W Sprengers, MD	+31887555555 ext 4195	r.w.sprengers@umcutrecht.nl
Contact: Marianne C Verhaar, MD, PhD	+31887555555 ext 3375	m.c.verhaar@umcutrecht.nl

Locations

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

Sponsors and Collaborators

UMC Utrecht

Catharijne Stichting

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	UMC Utrecht

More Information

Additional Information:

Information about the JUVENTAS Trial This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	UMC Utrecht ( dr. M.C. Verhaar )
Study ID Numbers:	JUVENTAS, 06/030, CS 06.007
Study First Received:	September 1, 2006
Last Updated:	February 1, 2008
ClinicalTrials.gov Identifier:	NCT00371371 History of Changes
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

Study placed in the following topic categories:

Arterial Occlusive Diseases
Fentanyl
Peripheral Vascular Diseases
Skin Diseases
Ulcer
Lidocaine
Vascular Diseases
Anesthetics
Gangrene

Pain
Ischemia
Midazolam
Calcium heparin
Necrosis
Skin Ulcer
Heparin
Leg Ulcer

Additional relevant MeSH terms:

Arterial Occlusive Diseases
Necrosis
Pathologic Processes
Peripheral Vascular Diseases
Skin Diseases
Vascular Diseases

Gangrene
Cardiovascular Diseases
Ischemia
Skin Ulcer
Leg Ulcer

ClinicalTrials.gov processed this record on September 09, 2009