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

October 3, 2007
July 5, 2011
October 2007
October 2012   (final data collection date for primary outcome measure)
Limb salvage/wound healing at t=6 months; Pain free walking distance [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Limb salvage/wound healing at t=6 months; Pain free walking distance [ Time Frame: 6 months ]
Complete list of historical versions of study NCT00539266 on ClinicalTrials.gov Archive Site
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 ]
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 ]
Not Provided
Not Provided
 
Autologous Bone Marrow-derived Mononuclear Cells for Therapeutic Arteriogenesis in Patients With Limb Ischemia
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

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.

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.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Intermittent Claudication
  • Peripheral Vascular Diseases
  • Biological: bone marrow derived mononuclear cells
    40 IM injections (calf muscle) of 1-8 10E9 mono nuclear cells
  • Biological: placebo
    40 IM injections (calf muscle) of placebo suspension
  • Active Comparator: 1
    non diabetic patients with Fontaine IIb-IV peripheral artery disease
    Intervention: Biological: bone marrow derived mononuclear cells
  • Placebo Comparator: 2
    non diabetic patients with Fontaine IIb-IV peripheral artery disease
    Intervention: Biological: placebo
  • Active Comparator: 3
    diabetic patients with Fontaine IIb-IV peripheral artery disease
    Intervention: Biological: bone marrow derived mononuclear cells
  • Placebo Comparator: 4
    diabetic patients with Fontaine IIb-IV peripheral artery disease
    Intervention: Biological: placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
108
October 2012
October 2012   (final data collection date for primary outcome measure)

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
Both
16 Years and older
No
Contact: Jan HN Lindeman, MD, PhD #31 (0)71 5263968 Lindeman@lumc.nl
Netherlands
 
NCT00539266
P07.058
No
Board of Directors, Leiden University Medical Centre
Leiden University Medical Center
Not Provided
Principal Investigator: Jan HN Lindeman, MD, PhD Leiden University Medical Center
Leiden University Medical Center
October 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP