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

ISRCTN	ISRCTN76049483
DOI	https://doi.org/10.1186/ISRCTN76049483
Secondary identifying numbers	N/A

Submission date: 16/07/2007
Registration date: 16/07/2007
Last edited: 31/12/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Jan H. Lindeman
Scientific

Leiden University Medical Centre
Department of Vascular Surgery
P.O. Box 9600
Leiden
2300 RC
Netherlands

Email	Lindeman@lumc.nl

Study information

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Scientific title	Intramuscular or combined intramuscular/intra-arterial administration of bone marrow mononuclear cells in patients with advanced limb ischaemia
Study objectives	The primary aim of our study was to test the feasibility and safety of exclusively intramuscular, and combined intramuscular/intra-arterial delivery of Bone marrow Mononuclear Cells (BMC) in patients with advanced limb ischaemia without conventional options for surgical or endovascular treatment.
Ethics approval(s)	Ethics approval received from the Medical Ethical Committee of the Leiden University Medical Centre on December 12, 2003 (ref: P03.149).
Health condition(s) or problem(s) studied	Bone marrow mononuclear cells in patients with advanced limb ischaemia
Intervention	Hospital admittance was planned in a short-stay setting (24 - 48 hours). The harvest procedure was performed according to standard protocols for bone marrow donation for allogenic transplantation. 750 millilitre bone marrow was collected from the posterior iliac crest under epidural or general anaesthesia. 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 re-infused to the patient. The mononuclear cells were implanted approximately 4 hours after bone marrow aspiration. The method of administration was randomly assigned to the patients using a random number table: 1. By local injection into the gastrocnemius muscle 2. By combined Intramuscular (IM) and Intra-Arterial (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 catheterisation of the superficial femoral artery (or profunda femoral artery in case of occlusion of the Superficial Femoral Artery [SFA]), performed according to the standard procedures within the Department of Radiology.
Intervention type	Other
Primary outcome measure	1. Wound healing/limb salvage (Fontaine 3/4), measured at 6 months 2. Pain-free walking distance (Fontaine 2), measured at 6 months
Secondary outcome measures	1. Ankle/brachial index, measured at 3, 6 and 12 months 2. Pain scores (Brief Pain Inventory), measured at 3, 6 and 12 months 3. Quality of Life (RAND-36), measured at 3, 6 and 12 months 4. Artery scores (angiogram), measured at 6 months 5. Limb salvage/wound healing and pain free walking distance at 3 and 12 months
Overall study start date	01/01/2004
Completion date	01/01/2006

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	25
Total final enrolment	16
Key inclusion criteria	1. Disabling claudication (Fontaines stages IIb/III or Rutherfords categories 3/4) or critical limb ischaemia (Fontaines stages IV or Rutherfords categories 5/6) despite greater than six months optimal medical therapy 2. Ineligibility for angioplasty or bypass procedures 3. Male of female, greater than 18 years old 4. Life expectancy greater than one year 5. Written informed consent
Key exclusion criteria	1. Candidates for angioplasty or bypass procedures 2. Inability to undergo bone marrow harvesting 3. Life threatening co-morbidity 4. International Normalised Ratio (INR) greater than 2 5. History of malignant disease in five years prior to treatment 6. Inability to undergo arterial catheterisation 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
Date of first enrolment	01/01/2004
Date of final enrolment	01/01/2006

Locations

Countries of recruitment

Netherlands

Study participating centre

Leiden University Medical Centre

Leiden
2300 RC
Netherlands

Sponsor information

Leiden University Medical Centre (LUMC) (The Netherlands)
Hospital/treatment centre

Department of Vascular Surgery
P.O. Box 9600
Leiden
2300 RC
Netherlands

Website	http://www.lumc.nl/english/start_english.html
"ROR"	https://ror.org/027bh9e22

Funders

Funder type

Hospital/treatment centre

Leiden University Medical Centre (LUMC) (The Netherlands)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/01/2010	31/12/2020	Yes	No

Editorial Notes

31/12/2020: The following changes have been made:
1. Publication reference added.
2. The final enrolment number has been added from the reference.