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

Phase 2

• Conditions: Peripheral Arterial Disease; Cardiovascular Diseases; Vascular Diseases
• Interventions: Drug: Allogeneic Mesenchymal Stromal Cell; Other: Placebo

• Registration Number: NCT03042572
• Lead Sponsor: Martin Teraa, MD, PhD

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-01-27
• Study First Submitted QC: 2017-02-01
• Study First Posted: 2017-02-03
• Status Verified: 2018-05
• Last Update Submitted: 2018-05-02
• Last Update Posted: 2018-05-03
• Study Start: 2018-12
• Primary Completion: 2020-12
• Study Completion: 2021-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Allogeneic Mesenchymal Stromal Cell	Allogeneic Mesenchymal Stromal Cell	Intramuscular Allogeneic Bone marrow-derived Mesenchymal Stromal Cell Injection
Placebo	Placebo	Intramuscular placebo injection

Primary Outcome Measures

Name	Time	Method
Therapy Success	6 months	Composite outcome measure considering mortality, limb status, clinical classification and changes in pain score. To be a "success" a subject must: A, be alive; B, be without a major amputation on the index limb; C, have not worsened in Rutherford classification or visual analog pain scale; and D, have improved in either Rutherford classification or visual analog pain scale. Subjects not meeting all of the criteria are classified as failures.

Secondary Outcome Measures

Name	Time	Method
Major amputation	2, 6, 12, 24, and 60 months	Amputation sited proximal from the ankle joint
Minor amputation	2, 6, 12, 24, and 60 months	Amputation sited distal from the ankle joint
Therapy Success	2, 6, 12, 24, and 60 months	Composite outcome measure considering mortality, limb status, clinical classification and changes in pain score. To be a "success" a subject must: A, be alive; B, be without a major amputation on the index limb; C, have not worsened in Rutherford classification or visual analog pain scale; and D, have improved in either Rutherford classification or visual analog pain scale. Subjects not meeting all of the criteria are classified as failures.
Mortality	2, 6, 12, 24, and 60 months	Mortality
Ulcer healing	2 and 6 months	Changes in the number and extent of leg ulcers,
Changes in pain	2, 6, 12, 24, and 60 months	Resolution of rest pain and alteration in visual analogue pain (VAS) score
Pain-free walking distance	2 and 6 months	Changes in pain free walking distance (treadmill at 3 km/h without incline)
Ankle-brachial index (ABI)	2 and 6 months	Alterations in ankle-brachial index (ABI)
Toe-brachial index (TBI)	2 and 6 months	Alterations in toe-brachial index (TBI)
Quality of life based on EuroQol 5D (EQ5D) questionnaire scores	2, 6, 12, 24, and 60 months	Alterations in quality of life assessed using EuroQoL 5D quality of life questionnaire
Quality of life based on Short Form 36 (SF36) questionnaire scores	2, 6, 12, 24, and 60 months	Alterations in quality of life assessed using Short Form 36 quality of life questionnaire
Clinical status according to Fontaine classification	2, 6, 12, 24, and 60 months	Alterations clinical status according to Fontaine classification
Clinical status according to Rutherford classification	2, 6, 12, 24, and 60 months	Alterations clinical status according to Rutherford classification

Trial Locations

Locations (1)

University Medical Center Utrecht; 🇳🇱 Utrecht, Netherlands