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

Phase 1

Completed

• Conditions: Gangrene; Leg Ulcer; Arterial Occlusive Diseases; Peripheral Vascular Diseases; Ischemia
• Interventions: Procedure: Bone marrow punction; Procedure: BM-MNC infusion; Procedure: Placebo infusion

• Registration Number: NCT00371371
• Lead Sponsor: 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.

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 Timeline

• Study Start: 2006-09
• Study First Submitted: 2006-09-01
• Study First Submitted QC: 2006-09-01
• Study First Posted: 2006-09-04
• Status Verified: 2012-12
• Primary Completion: 2012-12
• Study Completion: 2012-12
• Last Update Submitted: 2012-12-12
• Last Update Posted: 2012-12-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 160

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BM-MNC	Bone marrow punction	autologous bone marrow-derived mononuclear cells
BM-MNC	BM-MNC infusion	autologous bone marrow-derived mononuclear cells
Placebo	Placebo infusion	Placebo
Placebo	Bone marrow punction	Placebo

Primary Outcome Measures

Name	Time	Method
major amputation	six months

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University Medical Center Utrecht (UMC Utrecht); 🇳🇱 Utrecht, Netherlands