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

July 5, 2011 updated by: Leiden University Medical Center

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

108

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Jan HN Lindeman, MD, PhD
  • Phone Number: #31 (0)71 5263968
  • Email: Lindeman@lumc.nl

Study Locations

  • Netherlands
      • Leiden, Netherlands, 2300RC
        • Recruiting
        • Leiden University Medical Center
        • Contact:
          • Jan HN Lindeman, MD, PhD
          • Phone Number: #31 (0)71 5263968
          • Email: Lindeman@lumc.nl

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Limb salvage/wound healing at t=6 months; Pain free walking distance
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
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
3, 6 and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Leiden University Medical Center

Investigators

  • Principal Investigator: Jan HN Lindeman, MD, PhD, Leiden University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2007

Primary Completion (Anticipated)

October 1, 2012

Study Completion (Anticipated)

October 1, 2012

Study Registration Dates

First Submitted

October 3, 2007

First Submitted That Met QC Criteria

October 3, 2007

First Posted (Estimate)

October 4, 2007

Study Record Updates

Last Update Posted (Estimate)

July 6, 2011

Last Update Submitted That Met QC Criteria

July 5, 2011

Last Verified

October 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P07.058

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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