Clinical trial NCT04433104: Umbilical Cord Mesenchymal Stem Cells Transplantation in the Treatment of Chronic Obstructive Pulmonary Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: COPD
Keywords: COPD
umbilical cord mesenchymal stem cells
Lead sponsor: Vinmec Research Institute of Stem Cell and Gene Technology
Sponsor class: OTHER
First posted: 2020-06-16
Enrollment: 40
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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. 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-, gender- 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 administrationassociated adverse events (AEs) and serious adverse events (SAEs). 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 post

Eligibility criteria: Inclusion Criteria:

* Diagnosed with COPD with stage B, C, or D according to GOLD 2019.
* Age between 40-75 years old.
* Both genders.

Exclusion Criteria:

* Smoker or less than 6 months of smoking cessation time.
* Asthma and other pulmonary-related diseases and injuries (including lung tuberculosis, restrictive lung disease, idiopathic pulmonary fibrosis, or lung cancer).
* Acute and/or active infection.
* Cancer.
* Patients with complex cardiovascular diseases (including valvular heart disease, cardiomyopathy, arrhythmia, congenital heart disease, hypertrophy syndrome).
* Liver and kidney failure.
* Pregnancy.
* Patients with life expectancy less than 6 months due to concomitant illness.
* Under immunosuppressive treatment within 8 weeks of the first screening visit.
* Patient diagnosed diabetes with HbA1C\>7%

Primary outcomes:
measure: Adverse events and serious adverse events
timeFrame: up to the 12-month period following treatment
Secondary outcomes:
measure: Quality of Life using Georges Respiratory Questionnaire
timeFrame: up to the 12-month period following treatment
measure: Chest CT
timeFrame: up to the 12-month period following treatment
measure: arterial blood gas analysis (pH)
timeFrame: up to the 12-month period following treatment
measure: arterial blood gas analysis (PaO2)
timeFrame: up to the 12-month period following treatment
measure: arterial blood gas analysis (PaCO2)
timeFrame: up to the 12-month period following treatment
measure: arterial blood gas analysis (BE)
timeFrame: up to the 12-month period following treatment
measure: arterial blood gas analysis (HCO3-)
timeFrame: up to the 12-month period following treatment
measure: Respiratory functions (FEV1)
timeFrame: up to the 12-month period following treatment
measure: Respiratory functions (FEV1/FVC)
timeFrame: up to the 12-month period following treatment
measure: Respiratory functions (VC)
timeFrame: up to the 12-month period following treatment
measure: Respiratory functions (TLC)
timeFrame: up to the 12-month period following treatment
measure: Respiratory functions (RV)
timeFrame: up to the 12-month period following treatment
measure: Respiratory functions (DLCO)
timeFrame: up to the 12-month period following treatment
measure: Respiratory functions (DLNO/DLCO)
timeFrame: up to the 12-month period following treatment
measure: inflammatory response (CRP)
timeFrame: up to the 12-month period following treatment
measure: inflammatory response (Pro-BNP)
timeFrame: up to the 12-month period following treatment
measure: inflammatory response (Troponin-T)
timeFrame: up to the 12-month period following treatment
measure: cytokine analysis from patients' plasma
timeFrame: up to the 12-month period following treatment
measure: modified medical research council
timeFrame: up to the 12-month period following treatment
Other outcomes:
Locations:
city: Hà Nội
country: Vietnam
facility: Vinmec International Hospital Times City
state: Hanoi
Study officials:
affiliation: Vinmec Research Institute of Stem Cell and Gene Technology
name: Duc Minh Hoang, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ribeiro-Paes JT, Bilaqui A, Greco OT, Ruiz MA, Marcelino MY, Stessuk T, de Faria CA, Lago MR. Unicentric study of cell therapy in chronic obstructive pulmonary disease/pulmonary emphysema. Int J Chron Obstruct Pulmon Dis. 2011 Jan 1;6:63-71. doi: 10.2147/COPD.S15292.
citation: Stessuk T, Ruiz MA, Greco OT, Bilaqui A, Ribeiro-Paes MJ, Ribeiro-Paes JT. Phase I clinical trial of cell therapy in patients with advanced chronic obstructive pulmonary disease: follow-up of up to 3 years. Rev Bras Hematol Hemoter. 2013;35(5):352-7. doi: 10.5581/1516-8484.20130113.
citation: Stolk J, Broekman W, Mauad T, Zwaginga JJ, Roelofs H, Fibbe WE, Oostendorp J, Bajema I, Versteegh MI, Taube C, Hiemstra PS. A phase I study for intravenous autologous mesenchymal stromal cell administration to patients with severe emphysema. QJM. 2016 May;109(5):331-6. doi: 10.1093/qjmed/hcw001. Epub 2016 Jan 27.
citation: Hoang DM, Nguyen KT, Nguyen AH, Nguyen BN, Nguyen LT. 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. BMJ Open. 2021 May 13;11(5):e045788. doi: 10.1136/bmjopen-2020-045788.