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Autologous Bone Marrow-derived Mononuclear Cells for Therapeutic Arteriogenesis in Patients With Limb Ischemia (ABC)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2007 by Leiden University Medical Center.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Leiden University Medical Center
ClinicalTrials.gov Identifier:
NCT00539266
First received: October 3, 2007
Last updated: July 5, 2011
Last verified: October 2007
History of Changes
  Purpose

The investigators propose confirm and extend the findings of open studies on the apparent efficacy of bone-marrow derived mononuclear cells for the induction of arteriogenesis in patients with severe claudication or critical leg ischemia and pay special attention to the influence of diabetic disease on the outcome of the study and to the possible pro-atherogenic/ pro-inflammatory effects of BM-MNC injections.


Condition Intervention Phase
Intermittent Claudication
Peripheral Vascular Diseases
 Biological: bone marrow derived mononuclear cells
Biological: placebo
 Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Autologous Bone Marrow-derived Mononuclear Cells for Therapeutic Arteriogenesis in Patients With Limb Ischemia A Double Blind, Placebo Controlled, Study in Diabetic and Non-diabetic Patients

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Leiden University Medical Center:

Primary Outcome Measures:
  • Limb salvage/wound healing at t=6 months; Pain free walking distance [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • quality of life (RAND-36), pain Scores (Brief Pain Inventory), tcO2 (wrist/ankle ratio) ABI Collateral artery scores (angiogram) at t=6 months, Limb salvage/wound healing at t= 3 and 12 months, Pain free walking distance at t=3 and 12 months, [ Time Frame: 3, 6 and 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 108
Study Start Date: October 2007
Estimated Study Completion Date: October 2012
Estimated Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
non diabetic patients with Fontaine IIb-IV peripheral artery disease
 Biological: bone marrow derived mononuclear cells
40 IM injections (calf muscle) of 1-8 10E9 mono nuclear cells
Placebo Comparator: 2
non diabetic patients with Fontaine IIb-IV peripheral artery disease
 Biological: placebo
40 IM injections (calf muscle) of placebo suspension
Active Comparator: 3
diabetic patients with Fontaine IIb-IV peripheral artery disease
 Biological: bone marrow derived mononuclear cells
40 IM injections (calf muscle) of 1-8 10E9 mono nuclear cells
Placebo Comparator: 4
diabetic patients with Fontaine IIb-IV peripheral artery disease
 Biological: placebo
40 IM injections (calf muscle) of placebo suspension

Detailed Description:

Although the safety and beneficial effects of intramuscular transplantation of bone marrow derived mononuclear cells procedure appear well documented, a number of critical question regarding application of BM-MNC for peripheral vascular disease remain to be answered. First, although the original study has been partially performed as semi-blinded study (patients with double sided claudication were recruited and blindly treated with BM-MNC in one leg and peripheral blood injections in the other leg), this approach does exclude a placebo effect. Second, although patients with mild diabetes were included in the protocol, the results for diabetic patients were not analyzed separately. Diabetic disease is characterized by monocyte and endothelial progenitor cell dysfunction and it is still unclear whether this approach is also effective in diabetic patients. Third, although six-month results are reported long-term efficacy has not been established yet.

To address these issues, the investigators now propose confirm and extend the findings from open studies in a randomized double-blind study in patients with severe claudication or critical leg ischemia and pay special attention to the influence of diabetic disease on the outcome of the study and to the possible pro-atherogenic/ pro-inflammatory effects of BM-MNC injections.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • persistent (>3 months) disabling claudication (Fontaine's stages IIb or Rutherford's categories 3, viz. pain free walking distance less than 100 meter) despite optimal therapy or critical limb ischemia (Fontaine's stages III/IV or Rutherford's categories 4-6)
  • ineligibility for angioplasty or bypass procedures
  • male of female, >18 years old
  • life expectancy > 1 year
  • written informed consent

Exclusion Criteria:

  • candidates for angioplasty or bypass procedures
  • inability to undergo bone marrow harvesting
  • any condition in the affected limb that is anticipated to require surgical intervention in the first weeks after BM-MNC treatment
  • life threatening co-morbidity
  • poorly controlled diabetes (HbA1C > 10%)
  • active malignancy in the 5 years prior to treatment
  • INR >1.5 at the time of bone-marrow harvest
  • bleeding diathesis
  • inability to undergo arterial catheterization
  • inability to follow the protocol and to comply with the follow up requirements
  • any other conditions that, in the opinion of the investigators, could interfere with the therapy or could pose a significant threat to the subject if the investigational therapy was to be initiated
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00539266

Contacts
Contact: Jan HN Lindeman, MD, PhD #31 (0)71 5263968 Lindeman@lumc.nl

Locations
Netherlands
Leiden University Medical Center Recruiting
Leiden, Netherlands, 2300RC
Contact: Jan HN Lindeman, MD, PhD     #31 (0)71 5263968     Lindeman@lumc.nl    
Sponsors and Collaborators
Leiden University Medical Center
Investigators
Principal Investigator: Jan HN Lindeman, MD, PhD Leiden University Medical Center
  More Information

No publications provided

Responsible Party: Board of Directors, Leiden University Medical Centre
ClinicalTrials.gov Identifier: NCT00539266     History of Changes
Other Study ID Numbers: P07.058
Study First Received: October 3, 2007
Last Updated: July 5, 2011
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Leiden University Medical Center:
Claudication
Critical limb ischemia
Cell therapy
Bone marrow

Additional relevant MeSH terms:
Intermittent Claudication
Ischemia
Vascular Diseases
Peripheral Vascular Diseases
Peripheral Arterial Disease
Arteriosclerosis
 Arterial Occlusive Diseases
Cardiovascular Diseases
Signs and Symptoms
Pathologic Processes
Atherosclerosis

ClinicalTrials.gov processed this record on May 23, 2013