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

Intermittent Claudication Clinical Trial

— ABC  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00539266
• Other study ID #: P07.058
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: October 3, 2007
• Last updated: July 5, 2011
• Start date: October 2007
• Est. completion date: October 2012

Study information

• Verified date: October 2007
• Source: Leiden University Medical Center
• Contact: Jan HN Lindeman, MD, PhD
• Phone: #31 (0)71 5263968
• Email: Lindeman[@]lumc.nl
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 108
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Intermittent Claudication
• Peripheral Arterial Disease
• Peripheral Vascular Diseases
• Vascular Diseases

Intervention

Biological:
• bone marrow derived mononuclear cells
40 IM injections (calf muscle) of 1-8 10E9 mono nuclear cells
• placebo
40 IM injections (calf muscle) of placebo suspension

Locations

Country	Name	City	State
Netherlands	Leiden University Medical Center	Leiden

Sponsors (1)

Lead Sponsor	Collaborator
Leiden University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Limb salvage/wound healing at t=6 months; Pain free walking distance		6 months	No
Secondary	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,		3, 6 and 12 months	No