Umbilical Cord Mesenchymal Stem Cells Transplantation in the Treatment of Chronic Obstructive Pulmonary Disease

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

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

Study Overview

• Status: Recruiting
• Conditions: COPD
• Intervention / Treatment: Biological: Umbilical Cord Mesenchymal Stem Cells transplantation; Drug: drug therapy according to Vietnamese MOHS procedure

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

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Duc Minh Hoang, PhD; Phone Number: (+84) 909 743 101; Email: v.duchm3@vinmec.com
• Study Contact Backup: Name: Anh Hai Nguyen, MD., PhD; Phone Number: (+84)968863668; Email: haianhnguyenbm@gmail.com

Study Locations

• Vietnam
  • Hanoi
    • Hà Nội, Hanoi, Vietnam, 100000
      • Recruiting
      • Vinmec International Hospital Times City
      • Contact: Anh Hai Nguyen, MD, PhD; Phone Number: (+84)968863668; Email: haianhnguyenbm@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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%

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (UC-MSC trasnplatation); 1 x 10^6 umbilical Cord Mesenchymal Stem Cells per body kg will transplant via the intravenous at baseline, and the second transplantation will be performed 3 months after the first transplantation and combination with Vietnames MOH procedure	Biological: Umbilical Cord Mesenchymal Stem Cells transplantation; Patients assigned to UC-MSC administration groups will receive two administrations at a dose of 1 million cells/kg patient body weight via the IV route with a 3-month intervening interval; Drug: drug therapy according to Vietnamese MOHS procedure; Salbutamol, Terbutaline
Other: control arm; drug therapy according to Vietnamese MOHS procedure	Drug: drug therapy according to Vietnamese MOHS procedure; Salbutamol, Terbutaline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events and serious adverse events	To assess safety, the number of AEs or SAEs during stem cell administration (72 h) at 3 months, 6 months, and 12 months after discharge will be evaluated	up to the 12-month period following treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life using Georges Respiratory Questionnaire	Georges Respiratory Questionnaire has scores range from 0 to 100, with higher scores indicating more limitations	up to the 12-month period following treatment
Chest CT	Changes of the lung fibrosis on chest CT at 6 months, and 12 months compared with baseline	up to the 12-month period following treatment
arterial blood gas analysis (pH)	arterial blood gas analysis (pH)	up to the 12-month period following treatment
arterial blood gas analysis (PaO2)	arterial blood gas analysis (PaO2)	up to the 12-month period following treatment
arterial blood gas analysis (PaCO2)	arterial blood gas analysis (PaCO2)	up to the 12-month period following treatment
arterial blood gas analysis (BE)	arterial blood gas analysis (BE)	up to the 12-month period following treatment
arterial blood gas analysis (HCO3-)	arterial blood gas analysis (HCO3-)	up to the 12-month period following treatment
Respiratory functions (FEV1)	Respiratory functions (FEV1)	up to the 12-month period following treatment
Respiratory functions (FEV1/FVC)	Respiratory functions (FEV1/FVC)	up to the 12-month period following treatment
Respiratory functions (VC)	Respiratory functions (VC)	up to the 12-month period following treatment
Respiratory functions (TLC)	Respiratory functions (TLC)	up to the 12-month period following treatment
Respiratory functions (RV)	Respiratory functions (RV)	up to the 12-month period following treatment
Respiratory functions (DLCO)	Respiratory functions (DLCO)	up to the 12-month period following treatment
Respiratory functions (DLNO/DLCO)	Respiratory functions (DLNO/DLCO)	up to the 12-month period following treatment
inflammatory response (CRP)	inflammatory response (CRP)	up to the 12-month period following treatment
inflammatory response (Pro-BNP)	inflammatory response (Pro-BNP)	up to the 12-month period following treatment
inflammatory response (Troponin-T)	inflammatory response (Troponin-T)	up to the 12-month period following treatment
cytokine analysis from patients' plasma	cytokine analysis from patients' plasma	up to the 12-month period following treatment
modified medical research council	modified medical research council (mMRC)	up to the 12-month period following treatment

Collaborators and Investigators

• Sponsor: Vinmec Research Institute of Stem Cell and Gene Technology
• Investigators: Principal Investigator: Duc Minh Hoang, PhD, Vinmec Research Institute of Stem Cell and Gene Technology

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2020
• Primary Completion (Anticipated): July 30, 2021
• Study Completion (Anticipated): December 25, 2021

Study Registration Dates

• First Submitted: June 9, 2020
• First Submitted That Met QC Criteria: June 11, 2020
• First Posted (Actual): June 16, 2020

Study Record Updates

• Last Update Posted (Actual): April 21, 2021
• Last Update Submitted That Met QC Criteria: April 19, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: COPD; umbilical cord mesenchymal stem cells
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: VinmecISC1916

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No