A Clinical Study of Mesenchymal Stem Cell Exosomes Nebulizer for the Treatment of ARDS

Acute Respiratory Distress Syndrome Clinical Trial

Official title:

A Multiple, Randomized, Double-blinded, Controlled Clinical Study of Allogeneic Human Mesenchymal Stem Cell Exosomes (hMSC-Exos) Nebulized Inhalation in the Treatment of Acute Respiratory Distress Syndrome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04602104
• Other study ID #: MEXARDS
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 30, 2020
• Est. completion date: September 2022

Study information

• Verified date: November 2020
• Source: Ruijin Hospital
• Contact: Jieming Qu, MD, PhD
• Phone: 86-21-64370045
• Email: jmqu0906[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate allogeneic human mesenchymal stem cell exosomes (hMSC-Exos) in the treatment of acute respiratory distress syndrome (ARDS)

Description:

According to the 2012 Berlin diagnostic criteria, there are currently more than 3 million ARDS patients worldwide, accounting for about 10% of patients in the intensive care unit (ICU). In recent years, the incidence of ARDS has increased significantly, which has significantly increased the social and economic burden. The impact of ARDS can even be compared with tumors, AIDS or myocardial infarction. There are the basic clinical treatments, such as using various ventilation methods to improve hypoxia and choosing alternative therapies to improve renal insufficiency. Therefore, there is still a lack of specific treatment measures.

Exosomes are naturally occurring nanosized vesicles and comprised of natural lipid bilayers with the abundance of adhesive proteins that readily interact with cellular membranes. Studies have confirmed that MSC-Exos can improve most of the pathological changes caused by lung infection, reduce pulmonary edema, reduce protein exudation, reduce alveolar inflammation, and clear bacterial infections. Thus, it brings new hope for the treatment of ARDS.

The purpose of this study is to evaluate allogeneic human mesenchymal stem cell exosomes (hMSC-Exos) in the treatment of acute respiratory distress syndrome (ARDS)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 169
• Est. completion date: September 2022
• Est. primary completion date: June 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. The subjects themselves or their family members voluntarily participate in this study and sign the informed consent form;

2. 18-70 years old, male or female;

3. Definitely diagnosed as acute respiratory distress syndrome (ARDS) (according to the Berlin definition and diagnostic criteria of ARDS);

4. Course of disease <96 hours after diagnosis;

5. Chest X-ray showed bilateral infiltration with pulmonary edema; no clinical manifestations of left ventricular hypertension, or pulmonary artery wedge pressure (PAOP) =18mmHg.

Exclusion Criteria:

1. Patients with severe allergic constitution;

2. Moderate to severe liver failure (children Pugh score > 12);

3. Patients with severe chronic respiratory diseases, PaCO2 > 50mmhg, and need home oxygen therapy;

4. Severe trauma occurred within 14 days before screening;

5. History of malignant tumor (patients with skin basal cell carcinoma in the past can be included);

6. They are undergoing hemodialysis or peritoneal dialysis;

7. The patients who had deep venous thrombosis or pulmonary embolism within 90 days;

8. Acute myocardial infarction occurred within 30 days;

9. Neuromuscular diseases that result in impaired natural ventilation include, but are not limited to, C5 or higher spinal cord injury, amyotrophic lateral sclerosis, Guillain Barre syndrome, and myasthenia gravis;

10. Obesity (BMI > 28);

11. Lung transplantation;

12. Bone marrow transplantation;

13. Active immunosuppression is defined as receiving immunosuppressive drugs or having a medical condition associated with immunodeficiency. These included: 1) HIV (AIDS or CD4 < 200 cells / mm3); 2) chemotherapy within 6 weeks before randomization; 3) immunosuppressive therapy, including maintenance glucocorticoid therapy (> 40) Results: 1) short term systemic steroid therapy (intravenous or oral) for less than 1 week, topical steroid for skin diseases; 4) absolute neutrophil count < 500 / mm3;

14. Patients undergoing extracorporeal circulation support (ECMO) or high frequency oscillatory ventilation;

15. They were not willing to receive lung protective ventilation (minimum tidal volume 6ml / kg pbw) or liquid management treatment;

16. Have a history of epilepsy, need continuous anticonvulsant therapy, or have received anticonvulsant therapy in the past 3 years;

17. The estimated survival time was less than 30 days;

18. Hepatitis B, hepatitis C, AIDS, syphilis patients;

19. Women of childbearing age are pregnant, lactating or pregnant within one year;

20. Those who could not understand the study protocol;

21. According to the judgment of the researchers, there were other situations in which the patients were not suitable to participate in the study (for example, there were factors to reduce the follow-up compliance, and the patients did not receive relevant supportive treatment, etc.).

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

Biological:
• low dose hMSC-Exos
basic treatment and 7 times aerosol inhalation of hMSC-Exos (2.0*10^8 particles at Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7)
• medium dose hMSC-Exos
basic treatment and 7 times aerosol inhalation of hMSC-Exos (8.0*10^8 particles at Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7)
• high dose hMSC-Exos
basic treatment and 7 times aerosol inhalation of hMSC-Exos (16.0*10^8 particles at Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7)
• Dosage 1of hMSC-Exos
basic treatment and 7 times aerosol inhalation of hMSC-Exos (a quarter of MTD/day at Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7)
• Dosage 2 of hMSC-Exos
basic treatment and 7 times aerosol inhalation of hMSC-Exos (MTD/day at Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7)
• No hMSC-derived exosomes
basic treatment and 7 times aerosol inhalation of normal saline (at Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7)

Locations

Country	Name	City	State
China	Ruijin Hospital, Medical School of Shanghai Jiaotong University	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Ruijin Hospital	Cellular Biomedicine Group Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse reaction	Incidence of adverse reaction	up to 14 days
Primary	TTCI	Time to Clinical improvement	up to 28 days
Primary	28-day mortality	28-day mortality	up to 28 days
Secondary	Murray lung injury score	The minimum value is 0 and the maximum are 16. Higher scores mean a worse outcome.	baseline and Day 1, Day 2, Day 3, Day 4, Day 5, Day6, Day7, Day14, Day28, Day60
Secondary	PaO2/FiO2	oxygen index: the ratio of alveolar oxygen partial pressure to fraction of inspired oxygen	baseline and Day 3, Day7, Day14, Day28, Day60
Secondary	SOFA score	The minimum value is 0 and the maximum are 48. Higher scores mean a worse outcome.	baseline and Day 1, Day 2, Day 3, Day 4, Day 5, Day6, Day7, Day14, Day28, Day60
Secondary	Apach? score	The minimum value is 0 and the maximum are 24. Higher scores mean a worse outcome.	baseline and Day 1, Day 2, Day 3, Day 4, Day 5, Day6, Day7, Day14, Day28, Day60
Secondary	The number of days the survivor was in ICU	The number of days the survivor was in ICU	up to 60 days