Allogeneic Mesenchymal Stromal Cells for Angiogenesis and Neovascularization in No-option Ischemic Limbs

Summary

The primary objective of this trial is to investigate whether intramuscular administration of allogeneic mesenchymal stromal cells (MSC) is safe and potentially effective, assessed as a composite outcome of mortality, limb status, clinical status (Rutherford classification) and pain score (visual analogue scale), in patients with no-option severe limb ischemia (SLI).

The investigators will conduct a double-blind, placebo-controlled randomized clinical trial to investigate the effect of allogeneic bone marrow(BM)-derived MSC in patients with SLI, who are not eligible for conventional surgical or endovascular therapies. The investigators intend to include 60 patients, who will be randomized to undergo 30 intramuscular injections with either BM-MSC (30 injection sites with 5\*10\^6 MSCs each) or placebo in the lower leg of the ischemic extremity. Primary outcome i.e. therapy success, a composite outcome considering mortality, limb status, clinical status (Rutherford classification) and changes in pain score, will be assessed at six months.

Conditions

• Peripheral Arterial Disease
• Cardiovascular Diseases
• Vascular Diseases

Interventions

DRUG

Allogeneic Mesenchymal Stromal Cell

Intramuscular allogeneic BM-MSC injection: MSCs will be extracted from BM of healthy volunteers, expanded with human platelet lysate, and stored. Patients will receive intramuscular allogeneic BM-MSC injections at 30 sites in the lower leg of the ischemic limb. Blinded syringes are provided and cell suspensions will be injected intramuscularly by an experienced operator into multiple sites (30 sites, 1-1.5cm in depth, volume of 1.0mL containing 5\*10\^6 MSC per site; total 150\*10\^6 BM-MSCs) in the ischemic lower extremity. Injections will be performed under IV analgesia (fentanyl) and sedation (midazolam) if necessary.

OTHER

Placebo

Intramuscular placebo injections. Patients will receive intramuscular placebo injections at 30 prespecified sites in the lower leg of the ischemic limb. Blinded syringes are provided and will be injected intramuscularly by an experienced operator into multiple sites (30 sites, 1-1.5cm in depth, volume of 1.0mL placebo per site) in the ischemic lower extremity. Injections will be performed under IV analgesia (fentanyl) and sedation (midazolam) if necessary.

Sponsors & Collaborators

• ZonMw: The Netherlands Organisation for Health Research and Development

  collaborator OTHER

• Martin Teraa, MD, PhD

  lead OTHER

Principal Investigators

• Marianne C Verhaar, MD, PhD · UMC Utrecht

• Gert Jan de Borst, MD, PhD · UMC Utrecht

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-12-31

Primary Completion

2020-12-31

Completion

2021-07-31

Countries

• Netherlands

Study Locations