Allogeneic human umbilical cord-derived mesenchymal stem/stromal cells for chronic obstructive pulmonary disease (COPD): study protocol for a matched case-control, phase I/II trial

Abstract

Introduction: The global prevalence of chronic obstructive pulmonary disease (COPD) is increasing, and it has become a major public health burden worldwide, including in Vietnam. A large body of preclinical and clinical studies supports the safety of mesenchymal stem/stromal cells (MSCs) in the treatment of lung injury, including COPD. The aim of this trial is to investigate the safety and potential therapeutic efficacy of allogeneic administration of umbilical cord-derived MSCs (UC-MSCs) as a supplementary intervention in combination with standard COPD medication treatments in patients with moderate-to-severe COPD based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2019 and Vietnam Ministry of Health's guidelines.

Methods and analysis: This matched case-control phase I/II trial is conducted at Vinmec Times City International Hospital, Hanoi, Vietnam between June 2020 and December 2021. In this study, 40 patients will be enrolled and assigned into two age-matched, gender-matched and COPD condition-matched groups, including a UC-MSC group and a control group. Both groups will receive standard COPD medication treatment based on the GOLD 2019 guidelines and the Vietnam Ministry of Health protocol. The UC-MSC group will receive two doses of thawed UC-MSC product with an intervention interval of 3 months. The primary outcome measures will include the incidence of prespecified administration-associated adverse events and serious adverse events. The efficacy will be evaluated based on the absolute changes in the number of admissions, arterial blood gas analysis, lung function and lung fibrosis via CT scan and chest X-ray. The clinical evaluation will be conducted at baseline and 3, 6 and 12 months postintervention.

Ethics and dissemination: Ethical approval was secured from the Ethical Committee of Vinmec International Hospital (number:166/2019/QĐ-VMEC) and Vietnam Ministry of Health (number:2002/QĐ-BYT). The results will be reported to trial collaborators, publication in peer-reviewed academic journals.

Trial registration number: NCT04433104.

Keywords: chronic airways disease; respiratory medicine (see thoracic medicine); transplant medicine.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Schematic of the study. Patients with COPD will be screened to enrol in the study. Patients from the control group will be assigned to a patient from the UC-MSC group once they meet all matched criteria based on age (±5 years), gender and COPD severity classification (GOLD 2019). AEs, adverse events; COPD, chronic obstructive pulmonary disease; GOLD, Global Initiative for Chronic Obstructive Lung Disease; SAEs, serious adverse events; UC-MSC, umbilical cord-derived mesenchymal stem/stromal cells.

Figure 2

Standard COPD medication treatment for both groups according to GOLD 2019 and Vietnam Ministry of Health Guideline. Matched patients with COPD will be treated using the same treatment based on their GOPD 2019 classification (groups A, B, C and D). Group A (not included in this study): a single bronchodilator will be used and based on the clinical assessments and persistence of the symptoms to continue/stop or replace by another bronchodilator. Group B: single LAMA or LABA will be initially used. If the symptoms are not reduced, a combination of both LAMA and LABA will be applied. Group C: a single LAMA drug will be used for initial treatment. If exacerbations occur, LAMA and LABA combination will be applied as priority. The LAMA+ICS will be applied in specific cases based on clinical assessment, as the ICS has been reported to have severe side effects on lung inflammation. Group D: Should start the treatment with LAMA. If the patient has CAT >20, LABA and LAMA will be used as initial treatment. LABA+ICS will be used as the initial treatment only when the patient has asthma COPD overlap or the patient’s eosinophil level >300. If exacerbation occurs after the initial treatment, the combination of LAMA, LABA, and ICS should be applied. Additional roflumilast should be used if FEV1 <50% and the patient has chronic bronchitis. Macrolide should be used if the patient is a former smoker. The red arrow indicates priority treatment. COPD, chronic obstructive pulmonary disease; GOLD, Global Initiative for Chronic Obstructive Lung Disease; ICS, inhaled corticosteroid; LABA, long-acting β agonists; LAMA, long-acting muscarinic antagonists; m-MRC, modified medical research council.