Allogeneic MSC Treatment for Pulmonary Emphysema

• Status: Recruiting
• Trial end date: 2022-06-01
• Target enrollment: 0
• Participant gender: All

Summary

Rationale: Pulmonary emphysema is a component of Chronic Obstructive Pulmonary Disease (COPD) characterized by chronic inflammation with neutrophils and monocytes mediating the tissue destruction under the regulation of various types of lymphocytes. Bone marrow-derived mesenchymal stromal cells have potential to halt the progressive inflammatory response as indicated by the investigator's pilot study (CCMO NL28562.000.09) .

Objective: To determine whether patients with emphysema develop anti-inflammatory and tissue repair responses by treatment with allogeneic bone marrow-derived mesenchymal stromal cells (MSC) from healthy donors.

Study design: an explorative double-blind, placebo-controlled randomized (2:1) trial in 30 patients with moderate to severe emphysema who are scheduled for two separate sessions for surgical lung volume reduction (LVRS). The study treatment is intravenous allogeneic MSC or placebo treatment in between the first and second surgical session. Randomisation will allocate 10 patients to receive 2 x 106 /kg body weight MSC in a range of 1.5 x 106 MSC/ kg to 2.5 x 106 MSC/ kg (at a maximum of 200 x106 MSC per study participant) iv (or 5 patients to receive placebo) at week 4 and 3 before the second LVRS, and will allocate 10 patients to receive 2 x 106 /kg body weight MSC in a range of 1.5 x 106 MSC/ kg to 2.5 x 106 MSC/ kg (at a maximum of 200 x106 MSC per study participant) iv (or 5 patients to placebo) at week 12 and 11 before the second LVRS.

Main study parameters/endpoints: the study has a co-primary endpoint. First, the difference in expression of CD31 on cells per micrometer alveolar septae present in lung tissue harvested at the second LVRS from patients who received MSC at 3 and 4 weeks prior to LVRS2 or placebo. Second, the difference between MSC and placebo treatment in change in CO diffusion capacity over a period of 3 years following LVRS2.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Leiden University Medical Center
• Collaborators: Erasmus Medical Center; VU University Medical Center

Criteria

Inclusion Criteria:

• Signed informed consent consistent with ICH-GCP guidelines and local legislation prior to participation in the trial;

• Scheduled for lung volume reduction surgery for emphysema as determined by a referring chest physician;

• Pre-bronchodilator measured FEV1 between 20% and 45% predicted; TLCO between 30% and 45% pred.; RV/TLC ≥ 50%;

• Patients in a stable clinical condition.

Exclusion Criteria:

• Significant cardiac failure;

• Active smoking, or < 6 months smoking cessation;

• Failure to complete pulmonary rehab program before randomization

• Women of child bearing potential;

• Any cancer treated in the previous 5 years;

• Women of child-bearing potential not using adequate contraception;

• Any other condition of the patient that the clinical investigator deemed harmful for study participation.