Randomized, double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of human umbilical cord MSC–derived exosomes (hUCMSC-Exos) in COVID-19–associated ARDS (Pilot study)

The objective of this study was to evaluate the safety and efficacy of human umbilical cord mesenchymal stem cell–derived exosomes (hUCMSC-Exos) in patients with COVID-19–induced acute respiratory distress syndrome (ARDS), with a particular focus on reducing inflammation, modulating the immune response, and improving clinical outcomes.

This study is a randomized, double-blind, placebo-controlled pilot clinical trial. Patients are assigned to either the intervention group (hUCMSC-Exos) or the control group (placebo), with all participants receiving standard therapy in addition to the assigned intervention or placebo."

This study is a randomized, double-blind, placebo-controlled clinical trial conducted at Razi Hospital, Ahvaz, Iran. The study process includes screening, obtaining informed consent, random allocation to either the intervention or control group, administration of a single intravenous dose of hUCMSC-Exos or placebo, and follow-up for up to 7 days to assess clinical and laboratory outcomes

Participants: 18–65 years, both sexes, COVID-19 positive, moderate to severe ARDS, requiring oxygen therapy, bilateral pulmonary infiltrates, written consent. Exclusions: malignancy, pregnancy, liver/kidney failure, lung surgery/transplant, autoimmune/metabolic disease, coagulation disorder, trauma, viral infection, concurrent trial, dialysis, bone marrow transplant, epilepsy, clotting disorder.

Group A will receive a single intravenous dose of hUCMSC-derived exosomes (5×10¹⁰ particles suspended in 2–5 mL PBS) in addition to standard therapy. Group B (control) will receive a placebo consisting of sterile PBS with an identical volume and route of administration, along with standard therapy.

The primary outcome is infusion safety and patients’ immune-inflammatory response

During the implementation of this trial, which coincided with the peak of the COVID-19 pandemic, numerous clinical studies with overlapping inclusion criteria were simultaneously underway in the country. This overlap created considerable competition for patient recruitment and substantially reduced the pool of eligible participants for the present study. Furthermore, the investigational therapy—human mesenchymal stem cell–derived exosomes—was being introduced for the first time in Iran. Owing to the novelty of this intervention and the lack of familiarity among patients and their families, many preferred to rely on more conventional treatment options, thereby limiting enrollment. In addition, this study was intentionally designed as a pilot trial, with the primary objectives of evaluating safety, assessing feasibility, and providing preliminary insights into therapeutic efficacy as a foundation for larger-scale investigations. Another major challenge pertained to the process of obtaining informed consent: many patients with ARDS were critically ill or unconscious, while quarantine restrictions made timely access to family members difficult. Collectively, these factors led to a reduced final sample size and necessitated the present update of the IRCT record.

Computer-generated sequence (SAS 9.1), stratified block, opaque sealed envelopes, allocation by independent blinded researcher.

Double-blind (patients, investigators, outcome assessors).

Some of the data can potentially be shared after de-identification of individuals.

The access period will begin 6 months after the publication of the results.

All people

Hospitals for clinical purposes and researchers for the accelerated advancement of projects.

Scientific responsibility for the clinical trial: Stem Cell and Regenerative Medicine Research Center, Iran University of Medical Sciences, Shahid Motahari Hospital.

A written request specifying the reasons for the need for the data.