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

NCT00539266 | Unknown Phase 2

• 1 other identifier: P07.058
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Intermittent Claudication; Peripheral Vascular Diseases

Keywords

Claudication; Critical limb ischemia; Cell therapy; Bone marrow

Outcome Measures

Primary Outcomes (1)

• Limb salvage/wound healing at t=6 months; Pain free walking distance

  6 months

Secondary Outcomes (1)

• 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

Study Arms (4)

1

ACTIVE COMPARATOR

non diabetic patients with Fontaine IIb-IV peripheral artery disease

Biological: bone marrow derived mononuclear cells

2

PLACEBO COMPARATOR

non diabetic patients with Fontaine IIb-IV peripheral artery disease

Biological: placebo

3

ACTIVE COMPARATOR

diabetic patients with Fontaine IIb-IV peripheral artery disease

Biological: bone marrow derived mononuclear cells

4

PLACEBO COMPARATOR

diabetic patients with Fontaine IIb-IV peripheral artery disease

Biological: placebo

Interventions

bone marrow derived mononuclear cells BIOLOGICAL

40 IM injections (calf muscle) of 1-8 10E9 mono nuclear cells

1; 3

placebo BIOLOGICAL

40 IM injections (calf muscle) of placebo suspension

2; 4

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Leiden University Medical Center: lead

Study Sites (1)

Leiden University Medical Center

Leiden, 2300RC, Netherlands

RECRUITING

Related Publications (2)

• Moazzami B, Mohammadpour Z, Zabala ZE, Farokhi E, Roohi A, Dolmatova E, Moazzami K. Local intramuscular transplantation of autologous bone marrow mononuclear cells for critical lower limb ischaemia. Cochrane Database Syst Rev. 2022 Jul 8;7(7):CD008347. doi: 10.1002/14651858.CD008347.pub4.

  PMID: 35802393 DERIVED

• Lindeman JHN, Zwaginga JJ, Kallenberg-Lantrua G, van Wissen RC, Schepers A, van Bockel HJ, Fibbe WE, Hamming JF. No Clinical Benefit of Intramuscular Delivery of Bone Marrow-derived Mononuclear Cells in Nonreconstructable Peripheral Arterial Disease: Results of a Phase-III Randomized-controlled Trial. Ann Surg. 2018 Nov;268(5):756-761. doi: 10.1097/SLA.0000000000002896.

  PMID: 30004916 DERIVED

MeSH Terms

Conditions

Intermittent Claudication; Peripheral Vascular Diseases; Chronic Limb-Threatening Ischemia

Condition Hierarchy (Ancestors)

Peripheral Arterial Disease; Vascular Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Ischemia

Study Officials

• Jan HN Lindeman, MD, PhD

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jan HN Lindeman, MD, PhD

CONTACT

#31 (0)71 5263968; Lindeman@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 3, 2007
• First Posted: October 4, 2007
• Study Start: October 1, 2007
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: July 6, 2011

Record last verified: 2007-10

Locations

NL (1)