Intramuscular or combined intramuscular/intra-arterial administration of bone marrow mononuclear cells in patients with advanced limb ischemia.

• Register: Netherlands Trial Register
• Last refreshed on: 27 May 2013
• Main ID: NTR997
• Date of registration: 13/06/2007
• Primary sponsor: Leiden University Medical Center (LUMC), Department of Vascular Surgery
• Public title: Intramuscular or combined intramuscular/intra-arterial administration of bone marrow mononuclear cells in patients with advanced limb ischemia.
• Scientific title: Intramuscular or combined intramuscular/intra-arterial administration of bone marrow mononuclear cells in patients with advanced limb ischemia. - N/A
• Date of first enrolment: 1/1/2004
• Target sample size: 25
• Recruitment status: complete
• URL: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=997
• Study type: intervention
• Study design: Randomised: Yes; Masking: None; Control: Not applicable; Group: [default]; Type: 2 or more arms, randomized

Countries of recruitment

The Netherlands

Contacts

• Name: Jan H. Lindeman

• Name: Jan H. Lindeman

Key inclusion & exclusion criteria

Inclusion criteria: 1. Disabling claudication (Fontaine?s stages IIb/III or Rutherford?s categories 3/4) or critical limb ischemia (Fontaine?s stages IV or Rutherford?s categories 5/6) despite > 6 months optimal medical therapy;

2. Ineligibility for angioplasty or bypass procedures;

3. Male of female, >18 years old;

4. Life expectancy > 1 year;

5. Written informed consent.

Exclusion criteria: 1. Candidates for angioplasty or bypass procedures;

2. Inability to undergo bone marrow harvesting;

3. Life threatening co-morbidity;

4. INR >2;

5. History of malignant disease in 5 years prior to treatment;

6. Inability to undergo arterial catheterization;

7. Inability to follow the protocol and to comply with the follow up requirements;

8. 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.


Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Limb ischemia, Stem cells, Bone marrow cells, Arteriogenesis

Intervention(s)

Hospital admittance was planned in a short-stay setting (24-48 hrs). The harvest procedure was performed according to standard protocols for bone marrow donation for allogenic transplantation. 750 milliliter bone marrow was collected from the posterior iliac crest under epidural or general anesthesia. The suspension was filtered and subsequently concentrated in a final volume of 40 mL. Upon concentration of the BMC-fraction, the erythrocyte fraction was collected separately and reinfused to the patient.

The mononuclear cells were implanted approximately 4 h after bone marrow aspiration. The method of administration was randomly assigned to the patients using a random number table: either by local injection into the gastrocnemius muscle or by combined IM+IA delivery. The investigators were not blinded for the assignment. In case of total IM delivery, we implanted 1 ml using a 26-gauge needle on 40 sites, 1.5 cm deep, using the full surface of the gastrocnemius muscle. In patients assigned to the combined treatment arm, the volume of each IM injection was 0.5 ml. The remaining 20 ml was slowly infused after selective catheterization of the superficial femoral artery (or profunda femoral artery in case of occlusion of the SFA), performed according to the standard procedures within the department of radiology.

Primary Outcome(s)

1. Wound healing / limb salvage (Fontaine 3/4);

2. Painfree walking distance (Fontaine 2).

Secondary Outcome(s)

1. Ankle/brachial index;

2. Brief Pain Inventory.

Secondary ID(s)

ISRCTN76049483

Source(s) of Monetary Support

Leiden University Medical Center (LUMC), Department of Vascular Surgery