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

IntroductionThe 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 analysisThis 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 disseminationEthical 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 numberNCT04433104.

Stem cell-based therapy for human diseases

“… 230 Although thorough assessments of the effectiveness of UC-MSCs are still in the early stages, the number of trials using UC-MSCs for the treatment of COPD is increasing steadily, with larger sample sizes and stronger designs (randomized or matched case–control studies), providing a data set strongly supporting the future applications of UC-MSCs. 231 …”

“…230 Although thorough assessments of the effectiveness of UC-MSCs are still in the early stages, the number of trials using UC-MSCs for the treatment of COPD is increasing steadily, with larger sample sizes and stronger designs (randomized or matched case-control studies), providing a data set strongly supporting the future applications of UC-MSCs. 231 The ongoing pandemic of the 21st century, the COVID-19 pandemic, emerged as a major pulmonary health problem worldwide, with a relatively high mortality rate. Numerous studies, reviews, and systematic analyses have been conducted to discuss and expand our knowledge of the virus and propose different mechanisms by which the virus could alter the immune system.…”

Regenerative and translational medicine in COPD: hype and hope

“…Another group from Vietnam published a phase I/II matched case-control trial to evaluate the safety and efficacy of allogeneic human UC-MSCs in patients with moderate-to-severe COPD ( clinicaltrials.gov identifier: NCT04433104) [ 73 ]. In this study, 40 patients were enrolled and assigned to two age-matched, gender-matched and COPD condition-matched groups (UC-MSC-treated group and control group).…”

“…H oang et al . [ 73 ] published a very well-designed phase I/II clinical trial of the safety and efficacy of UC-MSC infusions in 20 COPD patients. In this clinical trial, patients received two intravenous infusions of 1×10 6 cells·kg −1 at a 3-month interval between the first and the second dose.…”

Chronic obstructive pulmonary disease and asthma: mesenchymal stem cells and their extracellular vesicles as potential therapeutic tools

“…This study provided data supporting that UC-MSC therapy is a safe and efficient treatment for COPD patients. However, it was not conducted as a randomized trial which is a drawback of this study [ 78 ]. Likewise, Bich and coworkers published a pilot clinical study registered in ISRCTN with a registration number of ISRCTN70443938 which explored the safety and efficiency of allogeneic UC-MSCs in 20 patients suffering from mild-to-severe COPD [ 79 ].…”