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

Martin Teraa, MD, PhD

Status and phase: Unknown; Phase 3; Phase 2

Conditions: Cardiovascular Diseases; Vascular Diseases; Peripheral Arterial Disease

Treatments: Drug: Allogeneic Mesenchymal Stromal Cell; Other: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT03042572

NL59038.000.16

Details and patient eligibility

About

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age > 18 years

• Severe Peripheral Artery Disease (PAD; Fontaine class III and / or IV):

  • Fontaine III (Rutherford 4): persistent, recurring rest pain requiring analgesia
  • Fontaine IV (Rutherford 5): non-healing ulcers present for > 4 weeks without evidence of improvement in response to conventional therapies

• Ankle brachial index < 0.6 or unreliable (non-compressible or not in proportion to the Fontaine classification)

• Not eligible for surgical or endovascular revascularization

• Written informed consent.

Exclusion criteria

• History of neoplasm or malignancy in the past 10 years
• Serious known concomitant disease with life expectancy of less than one year
• Rutherford 6 in which amputation on the short term (within 1-2 weeks) is inevitable
• Pregnancy or unwillingness to use adequate contraception during study
• Uncontrolled acute or chronic infection with systemic symptoms
• Follow-up impossible.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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60 participants in 2 patient groups, including a placebo group

Allogeneic Mesenchymal Stromal Cell

Experimental group

Description:

Intramuscular Allogeneic Bone marrow-derived Mesenchymal Stromal Cell Injection

Treatment:

Drug: Allogeneic Mesenchymal Stromal Cell

Placebo

Placebo Comparator group

Description:

Intramuscular placebo injection

Treatment:

Other: Placebo