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# Registration date Revision Id
2 2025-08-26, 1404/06/04 353252
1 2021-04-19, 1400/01/30 179252
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  • Protocol summary

    The use of mesenchymal stem cells-derived exosomes that were cultured in an inflammatory niche, can have beneficial effects in preventing or reducing cytokine storms due to the high modulating potential of the immune system, and reduce the complications and mortality of this disease.
    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.
    استفاده از اگزوزوم های سلولهای بنیادی مزانشیمی رشد یافته در نیچ التهابی با توجه به پتانسیل بالای تعدیل کنندگی سیستم ایمنی بدن، می تواند اثرات مفیدی در جلوگیری یا کاهش طوفان سایتوکاینی و کاهش عوارض و مرگ و میر این بیماری داشته باشد.
    هدف مطالعه ارزیابی ایمنی و اثربخشی اگزوزوم‌های مشتق از سلول‌های بنیادی مزانشیمی بند ناف انسانی (hUCMSC-Exos) در بیماران مبتلا به سندرم زجر تنفسی حاد (ARDS) ناشی از کووید-19، با تمرکز بر کاهش التهاب، تعدیل پاسخ ایمنی و بهبود شاخص‌های بالینی.
    A controlled trial with parallel groups, double-blind, randomized, phases 1 and 2 on 72 patients. The random sequence table was used to randomize the blocks.
    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."
    کارآزمایی بالینی دارای گروه کنترل، با گروه های موازی ، دو سویه کور ، تصادفی شده، فازهای 1و 2 بر روی 72 بیمار. برای تصادفی سازی از بلوک ها از نرم افزار جدول توالی تصادفی استفاده شد.
    این مطالعه یک کارآزمایی بالینی پایلوت، تصادفی‌سازی شده، دوسوکور و کنترل‌شده با دارونما هست. بیماران به گروه مداخله (hUCMSC-Exos) و کنترل (دارونما) تقسیم می شوند و همه علاوه بر مداخله یا دارونما، درمان استاندارد دریافت می کنند.
    In the Stem Cell Center for Excellence of Iran University of Medical Sciences, Stem cells will be cultured in DMEM/F12 with 10% serum. The inflammatory niche will be provided with interleukin 1-beta. Ultracentrifugation purifies the extracellular vesicles of the cell culture supernatant. Exosomes are resolved in PBS and after the Quality Control tests will be prescribed at 100 million/kg. The patient, treating physician, and the physician who follow-up are blinded.
    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
    در مرکز جامع سلول های بنیادی دانشگاه علوم پزشکی ایران سلول های بنیادی در محیط DMEM/F12 با 10 درصد سرم کشت داده خواهد شد و با اینترلوکین 1 بتا محیط التهابی شبیه سازی می گردد. برای تخلیص وزیکول های خارج سلولی مایع رویی کشت سلول از اولتراسانتریفوژ استفاده خواهد شد. رسوب اگزوزوم در PBS حل و نگهداری می شود و پس از کنترل کیفی به تعداد 100 میلیون به ازای هر کیلو وزن بیمار تجویز خواهد شد. بیمار، پزشک درمانگر و پیگیری کننده وضعیت بیمار کورسازی می شوند.
    این مطالعه یک کارآزمایی بالینی تصادفی‌سازی شده، دوسوکور و کنترل‌شده با دارونما در بیمارستان رازی، اهواز، ایران هست. فرآیند شامل غربالگری، اخذ رضایت آگاهانه، تخصیص تصادفی به گروه مداخله یا کنترل، تزریق یک دوز وریدی hUCMSC-Exos یا دارونما، و پیگیری تا ۷ روز برای ارزیابی نتایج بالینی و آزمایشگاهی می باشد.
    Inclusion Criteria: 1- Definitive infection with COVID-19 confirmed by PCR 2- Acute respiratory distress Syndrome of moderate to severe type (PaO2/ FiO2 <200mmHg) 3- Age between 18 to 65 years from both Sexes 4- No Participation in another clinical trial during this study 5- Written informed consent Exclusion Criteria: 1- Malignant diseases 2- Pregnancy 3- Symptoms or history of liver or kidney failure 4- History of lung surgery or Lung transplantation 5- Having an autoimmune disease or Metabolic disorders 6- Severe trauma occurred within 14 days 7- Who are undergoing hemodialysis or peritoneal dialysis
    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.
    شرایط ورود: 1- ابتلای قطعی به کووید 19 تائید شده توسط PCR 2- سندروم دیسترس تنفسی حاد از نوع متوسط و شدید (PaO2/ FiO2 <200mmHg - 3- بازه سنی 18 تا 65 سال از هر دو جنس 4- عدم مشارکت در کارآزمایی بالینی دیگر در طول این مطالعه 5- رضایت کتبی آگاهانه شرایط عدم ورود: 1- ابتلا به بیماریهای بدخیم 2- بارداری 3- علایم یا سابقه نارسایی کبدی یا کلیوی 4- سابقه جراحی روی ریه یا پیوند ریه 5- ابتلا به بیماری خود ایمنی یا اختلالات متابولیک 6- طی 14 روز قبل ترومای شدید داشته باشد 7- کسانیکه همودیالیز می شوند یا دیالیز صفاقی دارند
    شرکت‌کنندگان: ۱۸–۶۵ سال، هر دو جنس، COVID-19 مثبت، ARDS متوسط تا شدید، نیاز به اکسیژن‌تراپی، ارتشاحات دوطرفه ریوی، رضایت کتبی. محرومیت‌ها: بدخیمی، بارداری، نارسایی کبدی/کلیوی، جراحی/پیوند ریه، بیماری خودایمنی/متابولیک، اختلال انعقادی، تروما، عفونت ویروسی، کارآزمایی همزمان، دیالیز، پیوند مغز استخوان، صرع، اختلال لخته شدن.
    1- Intravenous injection of 500ml normal saline contains umbilical cord mesenchymal stem cell-derived Exosomes 2- Intravenous injection of normal saline
    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.
    1- اگزوزوم های سلول های بنیادی مزانشیمی بندناف در 500 میلی لیتر نرمال سالین با تزریق وریدی 2- تزریق وریدی نرمال سالین
    گروه A یک دوز وریدی از hUCMSC-Exos (۵×۱۰¹⁰ ذره در ۲–۵ میلی‌لیتر PBS) دریافت می کنند، علاوه بر درمان استاندارد. گروه B (کنترل) دارونما (PBS استریل) مشابه حجم و روش تزریق دریافت می کنند، همراه با درمان استاندارد
    Adverse reaction and severe adverse reaction; Time to clinical improvement
    The primary outcome is infusion safety and patients’ immune-inflammatory response
    واکنش جانبی و واکنش جانبی شدید ؛ زمان بهبود بالینی
    پیامد اصلی ایمنی تزریق و پاسخ ایمنی-التهابی بیماران است.
  • General information

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    2021-03-25, 1400/01/05
    2021-05-20, 1400/02/30
    2021-06-21, 1400/03/31
    2021-09-22, 1400/06/31
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    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.
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    در زمان اجرای این تحقیق و هم‌زمان با اوج همه‌گیری کووید-۱۹، تعداد زیادی از کارآزمایی‌های بالینی با معیارهای ورود مشابه در کشور در حال انجام بودند که این همپوشانی موجب رقابت بین طرح‌ها و در نتیجه کاهش تعداد بیماران واجد شرایط برای مطالعه حاضر شد. از سوی دیگر، نوآورانه بودن درمان با اگزوزوم‌های مشتق از سلول‌های بنیادی مزانشیمی که برای نخستین‌بار در ایران انجام می‌شد، باعث شد بسیاری از بیماران و خانواده‌های آنان به دلیل عدم آشنایی با این روش، تمایل کمتری برای ورود به مطالعه داشته باشند. علاوه بر این، مطالعه حاضر به‌عنوان یک کارآزمایی پایلوت طراحی گردید تا ضمن بررسی ایمنی، امکان‌سنجی اجرا و ارزیابی اولیه اثربخشی درمان، زمینه برای مطالعات بزرگ‌تر فراهم شود. همچنین مشکلات قابل توجهی در روند اخذ رضایت آگاهانه وجود داشت، چرا که بسیاری از بیماران مبتلا به ARDS در وضعیت بحرانی یا ناهشیار بودند و به دلیل محدودیت‌های ناشی از شرایط قرنطینه، خانواده‌های آنان نیز به‌سختی در دسترس قرار می‌گرفتند. مجموع این عوامل موجب شد حجم نمونه نهایی کاهش یافته و بروزرسانی در سامانه IRCT ضرورت یابد.
    Exosome therapy in COVID-19 patients
    Umbilical cord exosomes for reducing inflammation in COVID-19 ARDS
    اگزوزوم درمانی بیماران COVID-19
    استفاده از اگزوزوم های بند ناف برای کاهش التهاب در ARDS ناشی از COVID-19
    Evaluation of the Safety and Efficiency of Mesenchymal Stem Cell Derived Exosomes in patients with ARDS of COVID-19; An interventional randomized double-blind controlled clinical trial: phase I and II
    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)
    سنجش ایمنی و اثربخشی درمانی اگزوزوم های مشتق از سلول های بنیادی مزانشیمی در بیماران مبتلا به ARDS ناشی از کووید 19؛ کارآزمایی بالینی مداخله ای شاهد دار تصادفی دو سوکور، فاز 1 و 2
    کارآزمایی بالینی تصادفی دوسوکور شاهددار با دارونما برای بررسی ایمنی و کارایی اگزوزوم های مشتق از سلولهای بنیادی مزانشیمی بند ناف انسانی (hUCMSC-Exos) در بیماران مبتلا به سندرم زجر تنفسی حاد (ARDS) ناشی از COVID-19 (مطالعه پایلوت)
    Acute respiratory distress Syndrome of moderate to severe type (PaO2/ FiO2 <200mmHg)
    Age range between 18 to 65 years
    Men and Women
    No participation in another clinical trial during this study
    Chest X-ray showed bilateral infiltration with pulmonary edema
    Definitive infection with COVID-19 confirmed by PCR
    Patients who have given themselves and their families a full explanation of the study process and have obtained informed written consent
    18 to 65 years
    Gender: Both
    PCR-confirmed COVID-19
    moderate-to-severe ARDS (PaO2/FiO2 < 200)
    SpO2 < 93% on oxygen
    bilateral infiltrates on imaging
    written informed consent
    سندروم دیسترس تنفسی حاد از نوع متوسط و شدید (PaO2/ FiO2 <200mmHg)
    بازه سنی 18 تا 65 سال
    زنان و مردان
    عدم مشارکت در کارآزمایی بالینی دیگر در طول این مطالعه
    تصویربرداری قفسه صدری نشاندهنده ی انفیلتراسیون دو سویه با ادم ریوی
    ابتلای قطعی به کووید 19 تائید شده توسط PCR
    بیمارانی که به خود و خانواده شان توضیحات کامل در مورد فرآیند مطالعه داده شده و رضایت کتبی آگاهانه از آنها اخذ شده است
    سن 18 تا 65 سال
    جنس هر دو
    تشخیص COVID-19 با PCR
    ARDS متوسط تا شدید (PaO2/FiO2 < 200)
    نیاز به اکسیژن و SpO2 < 93%
    ارتشاح دوطرفه در تصویربرداری
    رضایت آگاهانه کتبی
    Cancer or malignant diseases
    Pregnant women or planning to become pregnant
    Symptoms or history of liver or kidney failure
    History of lung surgery or Lung transplantation
    Having an autoimmune disease
    Infectious viral infection
    Proven blood clotting disorders
    Participate in other clinical trials simultaneously
    Severe trauma occurred within 14 days before screening
    They are undergoing hemodialysis or peritoneal dialysis
    Bone marrow transplantation
    Have a history of epilepsy, need continuous anticonvulsant therapy
    Malignancy
    pregnancy
    hepatic/renal failure
    lung or bone marrow transplant
    autoimmune/metabolic disease
    dialysis
    contagious infection
    active epilepsy
    coagulopathy
    ابتلا به سرطان یا بیماریهای بدخیم
    زنان باردار یا در حال برنامه ریزی برای بارداری
    علایم یا سابقه نارسایی کبدی یا کلیوی
    سابقه جراحی روی ریه یا پیوند ریه
    ابتلا به بیماری خود ایمنی
    ابتلا به عفونت های ویروسی مسری
    اختلالات ثابت شده انعقاد خون
    شرکت در کارآزمایی بالینی دیگر به طور همزمان
    ترومای شدید در طی 14 روز قبل از غربالگری
    کسانیکه همودیالیز می شوند یا دیالیز صفاقی دارند
    پیوند مغز استخوان
    سابقه ی صرع و نیاز به درمان مداوم ضد تشنج
    بدخیمی
    بارداری
    نارسایی کبد/کلیه
    پیوند ریه یا مغز استخوان
    بیماری خودایمنی/متابولیک
    دیالیز
    عفونت مسری
    صرع فعال
    اختلالات انعقادی
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    Single IV dose of hUCMSC-derived exosomes (5×10^10 particles in 2–5 mL PBS) + standard of care
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    مداخله: یک دوز وریدی اگزوزومهای مشتق از سلولهای بنیادی مزانشیمی بند ناف انسانی 5×10^10 particles in 2–5 mL PBS) مراقبت استاندارد
    In this study, the Stratified Block Randomization method is used to randomize patients in the intervention and control groups. Because patients with different intensities are in the study, classification is based on the type of need or lack of need for respiratory support. Patients who need respiratory support in the form of mechanical ventilation are classified in group A and patients who need nasal cannula or do not need respiratory support are classified in group B. The blocks used are of sizes 2, 4, and 8, and based on the probable number of people participating in the study with any severity of the disease, blocks with the appropriate volume are used to generate random codes. In order to place patients in control and intervention groups, a random sequence table is created with the help of SAS 9.1 software. Each patient is assigned a completely random sequence number, and random numbers are placed in envelopes (exactly the same, completely closed, with no transparency to view the contents of the envelope). Patients choose one of the envelopes as they wish. Envelopes are kept by a researcher, who does not participate in the study and is not aware of the type of study until the data is collected. Only in case of severe complications, the researcher will be notified through the main project partner to open the relevant envelope.
    Computer-generated sequence (SAS 9.1), stratified block, opaque sealed envelopes, allocation by independent blinded researcher.
    در این مطالعه از روش Stratified Block Randomization برای تصادفی کردن بیماران در گروه مداخله و کنترل استفاده می شود. از آنجا که بیماران با شدت های مختلف در مطالعه هستند، بر اساس نوع نیاز یا عدم نیاز به حمایت تنفسی طبقه بندی صورت می گیرد. بیمارانی که به حمایت تنفسی به صورت ونتیلاسیون مکانیکی نیاز دارند در گروه A و بیمارانی که به کانولای بینی نیاز داشته و یا نیازی به حمایت تنفسی ندارند در گروه B طبقه بندی میشوند. بلوک های استفاده شده از اندازه های2، 4 و 8 تایی می باشند و براساس تعداد احتمالی افراد شرکت کننده در مطالعه با هر شدت بیماری، بلوک ها با حجم مناسب برای تولید کد های تصادفی استفاده می شود. جهت قرار دادن بیماران به گروه های کنترل و مداخله، به کمک نرم افزار SAS 9.1 software جدول توالی تصادفی ایجاد می شود. به هر بیمار یک شماره توالی به صورت کاملا تصادفی اختصاص داده می شود و اعداد تصادفی در پاکت هایی (کاملا مشابه، کاملا بسته، عدم شفافیت برای مشاهده محتوای پاکت) قرار داده میشوند. بیماران از میان پاکت ها یکی را به دلخواه انتخاب می کنند. پاکت ها توسط یک محقق، که در مطالعه شرکت نمی کند و نسبت به نوع مطالعه آگاهی ندارد، تا زمان جمع آوری داده ها نگهداری میشوند. تنها در صورت بروز عوارض شدید، محقق از طریق همکار اصلی طرح مطلع می شود که پاکت مربوطه را باز کند.
    تولید توالی اعداد تصادفی با نرم افزار SAS 9.1، مسدود طبقه بندی شده، پاکت های مات و کدگذاری شده، تخصیص توسط پژوهشگر مستقل.
    In this study, the participant in the intervention, his / her clinical caregiver, trial researcher, and outcome assessor did not know that they were prescribing the intervention drug or placebo.
    Double-blind (patients, investigators, outcome assessors).
    در این مطالعه شرکت کننده در مداخله، مراقب بالینی وی، محقق کارآزمایی و ارزیابی کننده ی پیامد نمی دانند که داروی مداخله و یا پلاسبو را تجویز می کنند.
    دوسوکور بیماران، پژوهشگران و ارزیابان پیامد
  • Primary outcomes

    #1
    Adverse reaction and severe adverse reaction
    Tumor necrosis factor alpha (TNF-α)
    واکنش جانبی و واکنش جانبی شدید
    فاکتور نکروزدهنده تومور آلفا
    At the beginning of the intervention and on days 2, 3, 4, 7 and 14 after the intervention
    Baseline to day 7
    در ابتدای مداخله و روزهای 2، 3، 4، 7 و 14 پس از مداخله
    از پایه تا روز 7
    Physical examination of pulmonary function test
    It is measured in serum blood samples using an ELISA kit.
    معاینه بالینی تست عملکرد تنفسی
    با استفاده از کیت ELISA در نمونه خون سرم اندازه‌گیری می شود.
    #2
    Murray lung injury score
    CRP
    امتیاز آسیب ریوی مورای
    پروتئین واکنشی سی یا سی. آر. پی
    Baseline and Days 1, 2, 3, 7, 14, 28, and 60 after intervention
    Change from baseline to day 7
    در ابتدا و روزهای 1، 2، 3، 7، 14، 28 و 60 پس از مداخله
    تغییر از پایه تا روز ۷
    Clinical checklist. The minimum value is 0 and the maximum is 16. Higher scores mean a worse outcome.
    Measurement is performed in serum using an immunoassay kit
    چک لیست بالینی. حداقل مقدار 0 و حداکثر 16 است. امتیازات بالاتر به معنای نتیجه بدتر است.
    اندازه‌گیری با کیت ایمونواسی در سرم
    #3
    PaO2/FiO2
    Serious Adverse Event (SAEs)
    PaO2/FiO2
    رویداد نامطلوب شدید
    Baseline and Day 3, Day7, Day14, Day28, Day60
    Serious adverse events up to day 7
    در ابتدا و روزهای 3، 7، 14، 28 و 60 پس از مداخله
    عوارض جانبی جدی تا روز ۷
    Oxygen index: the ratio of alveolar oxygen partial pressure to fraction of inspired oxygen
    Recorded from medical records and direct observation
    شاخص اکسیژن: نسبت فشار جزئی اکسیژن آلوئول به کسر اکسیژن گرفته شده
    ثبت از پرونده بالینی و مشاهده مستقیم
    #4
    The number of days the survivor was out of ICU
    IL-6
    تعداد روزهایی که بازمانده از ICU خارج شده است
    اینترلوکین 6
    60 Days
    Change from baseline to day 7
    60 روز
    تغییر از پایه تا روز ۷
    The number of days the survivor was out of ICU
    Measurement is performed in serum using an ELISA kit.
    تعداد روزهایی که بازمانده خارج از ICU باشد
    اندازه‌گیری با ELISA در سرم
    #5
    Blood biochemistry (CRP)
    CD3+, CD4+, CD8+ lymphocytes
    بیوشیمی خون (سی آر پی)
    لنفوسیت های +CD3+, CD4+, CD8
    Baseline, day 5, 10, 20
    Change from baseline to day 7
    در ابتدا و روزهای 5، 10 و 20
    تغییر از پایه تا روز ۷
    C-reactive protein (CRP, mg/mL) concentration in the plasma will be measured.
    Measurement is performed using a flow cytometry device.
    غلظت پروتئین واکنشگر C (میلی گرم در میلی لیتر) در پلاسما سنجش خواهد شد
    سنجش با دستگاه فلوسایتومتری
    #6
    empty
    D-dimer
    empty
    دی دایمر
    empty
    Changes from baseline to day 7
    empty
    تغییرات از پایه تا روز ۷
    empty
    Measurement is performed using the ELISA method
    empty
    اندازه‌گیری با روش‌ الایزا
    #7
    empty
    PRIEST score
    empty
    PRIEST score
    empty
    Change up to day 7
    empty
    تغییر تا روز ۷
    empty
    Assessment is performed by the treating physician according to standard guidelines.
    empty
    ارزیابی توسط پزشک معالج طبق دستورالعمل استاندارد
    #8
    empty
    Chest imaging
    empty
    عکس قفسه سینه
    empty
    Changes on day 3
    empty
    تغییرات روز ۳
    empty
    Assessment is performed using chest radiography and radiological interpretation.
    empty
    با رادیوگرافی قفسه سینه و تفسیر رادیولوژی
    #9
    empty
    Length of hospital stay
    empty
    مدت بستری
    empty
    Until discharge.
    empty
    تا زمان ترخیص
    empty
    Recorded from the clinical file
    empty
    ثبت از پرونده بالینی
  • Intervention groups

    #1
    Intervention group: Phase one: 12 patients with COVID-19 in two groups of 6 with Acute Respiratory Distress Syndrome (ARDS, each group includes intervention groups of 3). Phase Two: 60 patients with COVID-19-ARDS in two groups of 30 controls and intervention. Classified A and B in both control and intervention groups - Exosome receiving group (intervention groups) • Injection material: Umbilical Cord Stem Cell-derived exosomes• Injection rate: 1 Billion exosomes per kilogram of body weight • Injection carrier: Saline • Injection site: Intravenous
    A total of 30 patients (15 in the intervention group and 15 in the control group) are randomly assigned in a 1:1 ratio. The intervention group receives a single intravenous dose of human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) at 5×10¹⁰ particles in 2–5 mL PBS along with standard care. The control group receives a placebo (PBS of equal volume) along with standard care. Randomization is block-stratified, and the study is double-blind, so patients, investigators, and outcome assessors are unaware of group allocation.
    گروه مداخله: فاز یک: 12 بیمار مبتلا به کووید-19 در دو گروه 6 نفره با بیماری دیسترس حاد تنفسی (ARDS، هر گروه شامل گروه های 3 نفره مداخله). فاز دو 60 بیمار مبتلا به کووید-19 در دو گروه 30 نفره کنترل و مداخله و دارای طبقه بندی A و B در هر دو گروه کنترل و مداخله. گروه دریافت کننده اگزوزوم (گروه های مداخله). ماده تزریق: اگزوزوم های مشتق از سلول های بنیادی بند ناف. مقدار تزریق: یک میلیارد اگزوزوم به ازای هر کیلوگرم وزن بدن. حامل تزریق: سالین. محل تزریق: داخل رگ.
    بیماران (۳۰ نفر، شامل ۱۵ بیمار در گروه مداخله و ۱۵ بیمار در گروه کنترل) به صورت تصادفی با نسبت ۱:۱ به دو گروه تخصیص می‌یابند. گروه مداخله یک دوز وریدی اگزوزوم‌های مشتق از سلول‌های بنیادی مزانشیمی بند ناف انسانی (۵×۱۰¹⁰ ذره در ۲–۵ میلی‌لیتر PBS) همراه با مراقبت استاندارد دریافت می‌کنند. گروه کنترل دارونما (PBS با حجم مشابه) به همراه مراقبت استاندارد دریافت می‌کند. تخصیص بیماران به صورت مسدود طبقهبندیشده و دوسوکور است، به طوری که بیماران، پژوهشگران و ارزیابان پیامدها از گروه‌ها آگاه نیستند.
  • Recruitment centers

    #1
    Name of recruitment center - English: Razi hospital
    Name of recruitment center - Persian: بیمارستان رازی
    Full name of responsible person - English: Reza Khedri
    Full name of responsible person - Persian: رضا خدری
    Street address - English: Amaniyeh, Felestin Street in front of the governorate
    Street address - Persian: امانیه، خیابان فلسطین روبروی فرمانداری
    City - English: Ahwaz
    City - Persian: اهواز
    Province: Khouzestan
    Country: Iran (Islamic Republic of)
    Postal code: 6196514941
    Phone: +98 61 3333 0500
    Fax:
    Email: Razi-hos@ajums.ac.ir
    Web page address:
    Name of recruitment center - English: Razi hospital
    Name of recruitment center - Persian: بیمارستان رازی
    Full name of responsible person - English: Reza Khedri
    Full name of responsible person - Persian: رضا خدری
    Street address - English: Amanieh, Palestine Street, opposite the Governorate.
    Street address - Persian: امانیه، خیابان فلسطین، روبروی فرمانداری
    City - English: Ahvaz
    City - Persian: اهواز
    Province: Khouzestan
    Country: Iran (Islamic Republic of)
    Postal code: 6196514941
    Phone: +98 61 3333 0500
    Fax:
    Email: Razi-hos@ajums.ac.ir
    Web page address:
    #2
    Name of recruitment center - English: Golestan Hospital
    Name of recruitment center - Persian: بیمارستان گلستان
    Full name of responsible person - English: Mofid Husseinzadeh
    Full name of responsible person - Persian: مفید حسین زاده
    Street address - English: کوی گلستان
    Street address - Persian: Golestan district
    City - English: Ahwaz
    City - Persian: اهواز
    Province: Khouzestan
    Country: Iran (Islamic Republic of)
    Postal code: 613683568
    Phone: +98 61 3374 3001
    Fax:
    Email: mofidhusseinzade@gmail.com
    Web page address:
    Name of recruitment center - English: Golestan Hospital
    Name of recruitment center - Persian: بیمارستان گلستان
    Full name of responsible person - English: Mofid Husseinzadeh
    Full name of responsible person - Persian: مفید حسین زاده
    Street address - English: Golestan Neighborhood
    Street address - Persian: کوی گلستان
    City - English: Ahvaz
    City - Persian: اهواز
    Province: Khouzestan
    Country: Iran (Islamic Republic of)
    Postal code: 613683568
    Phone: +98 61 3374 3001
    Fax:
    Email: mofidhusseinzade@gmail.com
    Web page address:
  • Sponsors / Funding sources

    #1
    contact.organization_id:
    Name of organization / entity - English: Tarmim Ava Baran Knowledge Based Company
    Name of organization / entity - Persian: شرکت دانش بنیان ترمیم آوای باران
    Full name of responsible person - English: Dr. Abbas Mohammadi Matin
    Full name of responsible person - Persian: دکتر عباس محمدی متین
    Street address - English: Floor 8, Block B, Paytakht Complex, Mirdamad Ave.
    Street address - Persian: میرداماد، مجتمع پایتخت، بلوک B، طبقه 8
    City - English: Tehran
    City - Persian: تهران
    Province: Tehran
    Country: Iran (Islamic Republic of)
    Postal code: 1417755362
    Phone: +98 21 8605 4062
    Fax:
    Email: Info@tarmimava.com
    Web page address:
    contact.organization_id:
    Name of organization / entity - English: Danesh Bonyan Company: Tarmim Avaye Baran
    Name of organization / entity - Persian: شرکت دانش بنیان ترمیم آوای باران
    Full name of responsible person - English: Dr. Abbas Mohammadi Matin
    Full name of responsible person - Persian: دکتر عباس محمدی متین
    Street address - English: Mirdamad, Paytakht Complex, Block B, 8th Floor
    Street address - Persian: میرداماد، مجتمع پایتخت، بلوک B، طبقه 8
    City - English: Tehran
    City - Persian: تهران
    Province: Tehran
    Country: Iran (Islamic Republic of)
    Postal code: 1417755362
    Phone: +98 21 8605 4062
    Fax:
    Email: Info@tarmimava.com
    Web page address:
    Tarmim Ava Baran Knowledge Based Company
    Danesh Bonyan Company: Tarmim Avaye Baran
  • Person responsible for general inquiries


    Name of organization / entity - English:
    Name of organization / entity - Persian:
    Full name of responsible person - English: Mehrdad Dargahi
    Full name of responsible person - Persian: مهرداد درگاهی
    Position - English: Professor Assistant
    Position - Persian: استادیار
    Latest degree: sub_specialist
    Area of specialty/work: 88
    Area of specialty/work title - English: Pulmonologist
    Area of specialty/work title - Persian: بیماری های ریه
    Street address - English: Razi Hospital, In front of Governorate, Felestin Street, Amaniyeh
    Street address - Persian: امانیه، خیابان فلسطین، روبروی فرمانداری، بیمارستان رازی
    City - English: Ahwaz
    City - Persian: اهواز
    Province: Khouzestan
    Province - English:
    Province - Persian:
    contact.provinces_available: 1
    Country: Iran (Islamic Republic of)
    Postal code: 6196514941
    Phone: +98 61 3333 3050
    Mobile: +98 916 612 6311
    Fax:
    Email: Dargahi-m@ajums.ac.ir
    Web page address:

    Name of organization / entity - English:
    Name of organization / entity - Persian:
    Full name of responsible person - English: Mehrdad Dargahi
    Full name of responsible person - Persian: مهرداد درگاهی
    Position - English: Assistant professor
    Position - Persian: استادیار
    Latest degree: sub_specialist
    Area of specialty/work: 88
    Area of specialty/work title - English: Pulmonologist
    Area of specialty/work title - Persian: بیماری های ریه
    Street address - English: Amaniyeh, Palestine Street, opposite the Governor’s Office, Razi Hospital
    Street address - Persian: امانیه، خیابان فلسطین، روبروی فرمانداری، بیمارستان رازی
    City - English: Ahvaz
    City - Persian: اهواز
    Province: Khouzestan
    Province - English:
    Province - Persian:
    contact.provinces_available: 1
    Country: Iran (Islamic Republic of)
    Postal code: 6196514941
    Phone: +98 61 3333 3050
    Mobile: +98 916 612 6311
    Fax:
    Email: Dargahi-m@ajums.ac.ir
    Web page address:
  • Person responsible for scientific inquiries


    Name of organization / entity - English:
    Name of organization / entity - Persian:
    Full name of responsible person - English: Alireza Shoae Hassani
    Full name of responsible person - Persian: علیرضا شعاع حسنی
    Position - English: Assistant Professor
    Position - Persian: استادیار
    Latest degree: phd
    Area of specialty/work: 88
    Area of specialty/work title - English: Cell Therapy and Regenerative Medicine
    Area of specialty/work title - Persian: سلول درمانی و پزشکی بازساختی
    Street address - English: Stem Cell and Regenerative Medicine Research center, Motahari hospital, Rashid Yasemi Ave., Valiasr Ave.
    Street address - Persian: ولیعصر، خ رشید یاسمی، بیمارستان مطهری، مرکز تحقیقات سلول های بنیادی و پزشکی بازساختی
    City - English: Tehran
    City - Persian: تهران
    Province: Tehran
    Province - English:
    Province - Persian:
    contact.provinces_available: 1
    Country: Iran (Islamic Republic of)
    Postal code: 1996835929
    Phone: +98 21 8877 0031
    Mobile: +98 912 145 4878
    Fax:
    Email: cell.therapy@yahoo.com
    Web page address:

    Name of organization / entity - English:
    Name of organization / entity - Persian:
    Full name of responsible person - English: Alireza Shoae Hassani
    Full name of responsible person - Persian: علیرضا شعاع حسنی
    Position - English: Assistant Professor
    Position - Persian: استادیار
    Latest degree: phd
    Area of specialty/work: 88
    Area of specialty/work title - English: Cell Therapy and Regenerative Medicine
    Area of specialty/work title - Persian: سلول درمانی و پزشکی بازساختی
    Street address - English: Valiasr, Rashid Yasemi St., Motahari Hospital, Stem Cell and Regenerative Medicine Research Center
    Street address - Persian: ولیعصر، خ رشید یاسمی، بیمارستان مطهری، مرکز تحقیقات سلول های بنیادی و پزشکی بازساختی
    City - English: Tehran
    City - Persian: تهران
    Province: Tehran
    Province - English:
    Province - Persian:
    contact.provinces_available: 1
    Country: Iran (Islamic Republic of)
    Postal code: 1996835929
    Phone: +98 21 8877 0031
    Mobile: +98 912 145 4878
    Fax:
    Email: cell.therapy@yahoo.com
    Web page address:
  • Person responsible for updating data


    Name of organization / entity - English:
    Name of organization / entity - Persian:
    Full name of responsible person - English: Mandana Pouladzadeh
    Full name of responsible person - Persian: ماندانا پولادزاده
    Position - English: Assistant Professor
    Position - Persian: استادیار
    Latest degree: specialist
    Area of specialty/work: 57
    Area of specialty/work title - English:
    Area of specialty/work title - Persian:
    Street address - English: Razi Hospital, In front of Governorate, Felestin Street, Amaniyeh
    Street address - Persian: امانیه، خیابان فلسطین، روبروی فرمانداری، بیمارستان رازی
    City - English: Ahwaz
    City - Persian: اهواز
    Province: Khouzestan
    Province - English:
    Province - Persian:
    contact.provinces_available: 1
    Country: Iran (Islamic Republic of)
    Postal code: 6196514941
    Phone: +98 61 3333 3050
    Mobile: +98 935 255 1705
    Fax:
    Email: mandanapouladzadeh@gmail.com
    Web page address:

    Name of organization / entity - English:
    Name of organization / entity - Persian:
    Full name of responsible person - English: Mandana Pouladzadeh
    Full name of responsible person - Persian: ماندانا پولادزاده
    Position - English: Assistant Professor
    Position - Persian: استادیار
    Latest degree: specialist
    Area of specialty/work: 57
    Area of specialty/work title - English:
    Area of specialty/work title - Persian:
    Street address - English: Amaniyeh, Palestine Street, opposite the Governor’s Office, Razi Hospital
    Street address - Persian: امانیه، خیابان فلسطین، روبروی فرمانداری، بیمارستان رازی
    City - English: Ahvaz
    City - Persian: اهواز
    Province: Khouzestan
    Province - English:
    Province - Persian:
    contact.provinces_available: 1
    Country: Iran (Islamic Republic of)
    Postal code: 6196514941
    Phone: +98 61 3333 3050
    Mobile: +98 935 255 1705
    Fax:
    Email: mandanapouladzadeh@gmail.com
    Web page address:
  • Sharing plan

    yes
    no
    Some of the data is potentially shareable after blinding persons
    Some of the data can potentially be shared after de-identification of individuals.
    Access period starts 6 months after the results are published
    The access period will begin 6 months after the publication of the results.
    Hospitals for medical purposes and researchers for faster development of projects
    Hospitals for clinical purposes and researchers for the accelerated advancement of projects.
    The person in charge of the scientific support of the clinical trial Stem Cell and Reconstructive Medicine Research Center, Iran University of Medical Sciences Shahid Motahari Hospital cell.therapy@yahoo.com
    Scientific responsibility for the clinical trial: Stem Cell and Regenerative Medicine Research Center, Iran University of Medical Sciences, Shahid Motahari Hospital.
    A written request stating the reasons for the need for the data
    A written request specifying the reasons for the need for the data.

Protocol summary

Study aim
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.
Design
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."
Settings and conduct
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/Inclusion and exclusion criteria
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.
Intervention groups
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.
Main outcome variables
The primary outcome is infusion safety and patients’ immune-inflammatory response

General information

Reason for update
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.
Acronym
IRCT registration information
IRCT registration number: IRCT20190101042197N2
Registration date: 2021-04-19, 1400/01/30
Registration timing: prospective

Last update: 2025-08-30, 1404/06/08
Update count: 1
Registration date
2021-04-19, 1400/01/30
Registrant information
Name
Alireza Shoae-Hassani
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 21 8877 0031
Email address
alirezashoae@gmail.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2021-05-20, 1400/02/30
Expected recruitment end date
2021-09-22, 1400/06/31
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
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)
Public title
Umbilical cord exosomes for reducing inflammation in COVID-19 ARDS
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
18 to 65 years Gender: Both PCR-confirmed COVID-19 moderate-to-severe ARDS (PaO2/FiO2 < 200) SpO2 < 93% on oxygen bilateral infiltrates on imaging written informed consent
Exclusion criteria:
Malignancy pregnancy hepatic/renal failure lung or bone marrow transplant autoimmune/metabolic disease dialysis contagious infection active epilepsy coagulopathy
Age
From 18 years old to 65 years old
Gender
Both
Phase
1
Groups that have been masked
  • Participant
  • Investigator
  • Outcome assessor
Sample size
Target sample size: 30
Randomization (investigator's opinion)
Randomized
Randomization description
Computer-generated sequence (SAS 9.1), stratified block, opaque sealed envelopes, allocation by independent blinded researcher.
Blinding (investigator's opinion)
Double blinded
Blinding description
Double-blind (patients, investigators, outcome assessors).
Placebo
Used
Assignment
Parallel
Other design features
Single IV dose of hUCMSC-derived exosomes (5×10^10 particles in 2–5 mL PBS) + standard of care

Secondary Ids

empty

Ethics committees

1

Ethics committee
Name of ethics committee
Research Ethics Committees of Ahvaz Jundishapur University of Medical Sciences
Street address
Deputy of Research and Technology Development, Jundishapur University of Medical Sciences, Ahvaz, Ground Floor, Room 4
City
Ahvaz
Province
Khouzestan
Postal code
1579461357
Approval date
2021-03-17, 1399/12/27
Ethics committee reference number
IR.AJUMS.REC.1399.954

Health conditions studied

1

Description of health condition studied
Acute Respiratory Distress Syndrome due to COVID-19
ICD-10 code
J80
ICD-10 code description
Acute respiratory distress syndrome

Primary outcomes

1

Description
Tumor necrosis factor alpha (TNF-α)
Timepoint
Baseline to day 7
Method of measurement
It is measured in serum blood samples using an ELISA kit.

2

Description
CRP
Timepoint
Change from baseline to day 7
Method of measurement
Measurement is performed in serum using an immunoassay kit

3

Description
Serious Adverse Event (SAEs)
Timepoint
Serious adverse events up to day 7
Method of measurement
Recorded from medical records and direct observation

4

Description
IL-6
Timepoint
Change from baseline to day 7
Method of measurement
Measurement is performed in serum using an ELISA kit.

5

Description
CD3+, CD4+, CD8+ lymphocytes
Timepoint
Change from baseline to day 7
Method of measurement
Measurement is performed using a flow cytometry device.

6

Description
D-dimer
Timepoint
Changes from baseline to day 7
Method of measurement
Measurement is performed using the ELISA method

7

Description
PRIEST score
Timepoint
Change up to day 7
Method of measurement
Assessment is performed by the treating physician according to standard guidelines.

8

Description
Chest imaging
Timepoint
Changes on day 3
Method of measurement
Assessment is performed using chest radiography and radiological interpretation.

9

Description
Length of hospital stay
Timepoint
Until discharge.
Method of measurement
Recorded from the clinical file

Secondary outcomes

empty

Intervention groups

1

Description
A total of 30 patients (15 in the intervention group and 15 in the control group) are randomly assigned in a 1:1 ratio. The intervention group receives a single intravenous dose of human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) at 5×10¹⁰ particles in 2–5 mL PBS along with standard care. The control group receives a placebo (PBS of equal volume) along with standard care. Randomization is block-stratified, and the study is double-blind, so patients, investigators, and outcome assessors are unaware of group allocation.
Category
Treatment - Other

2

Description
Control group: Conventional treatments used in Acute Respiratory Distress Syndrome
Category
Placebo

Recruitment centers

1

Recruitment center
Name of recruitment center
Razi hospital
Full name of responsible person
Reza Khedri
Street address
Amanieh, Palestine Street, opposite the Governorate.
City
Ahvaz
Province
Khouzestan
Postal code
6196514941
Phone
+98 61 3333 0500
Email
Razi-hos@ajums.ac.ir

2

Recruitment center
Name of recruitment center
Golestan Hospital
Full name of responsible person
Mofid Husseinzadeh
Street address
Golestan Neighborhood
City
Ahvaz
Province
Khouzestan
Postal code
613683568
Phone
+98 61 3374 3001
Email
mofidhusseinzade@gmail.com

Sponsors / Funding sources

1

Sponsor
Name of organization / entity
Danesh Bonyan Company: Tarmim Avaye Baran
Full name of responsible person
Dr. Abbas Mohammadi Matin
Street address
Mirdamad, Paytakht Complex, Block B, 8th Floor
City
Tehran
Province
Tehran
Postal code
1417755362
Phone
+98 21 8605 4062
Email
Info@tarmimava.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Danesh Bonyan Company: Tarmim Avaye Baran
Proportion provided by this source
100
Public or private sector
Private
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Other

Person responsible for general inquiries

Contact
Name of organization / entity
Ahvaz University of Medical Sciences
Full name of responsible person
Mehrdad Dargahi
Position
Assistant professor
Latest degree
Subspecialist
Other areas of specialty/work
Pulmonologist
Street address
Amaniyeh, Palestine Street, opposite the Governor’s Office, Razi Hospital
City
Ahvaz
Province
Khouzestan
Postal code
6196514941
Phone
+98 61 3333 3050
Email
Dargahi-m@ajums.ac.ir

Person responsible for scientific inquiries

Contact
Name of organization / entity
Iran University of Medical Sciences
Full name of responsible person
Alireza Shoae Hassani
Position
Assistant Professor
Latest degree
Ph.D.
Other areas of specialty/work
Cell Therapy and Regenerative Medicine
Street address
Valiasr, Rashid Yasemi St., Motahari Hospital, Stem Cell and Regenerative Medicine Research Center
City
Tehran
Province
Tehran
Postal code
1996835929
Phone
+98 21 8877 0031
Email
cell.therapy@yahoo.com

Person responsible for updating data

Contact
Name of organization / entity
Ahvaz University of Medical Sciences
Full name of responsible person
Mandana Pouladzadeh
Position
Assistant Professor
Latest degree
Specialist
Other areas of specialty/work
Emergency Medicine
Street address
Amaniyeh, Palestine Street, opposite the Governor’s Office, Razi Hospital
City
Ahvaz
Province
Khouzestan
Postal code
6196514941
Phone
+98 61 3333 3050
Email
mandanapouladzadeh@gmail.com

Sharing plan

Deidentified Individual Participant Data Set (IPD)
Yes - There is a plan to make this available
Study Protocol
No - There is not a plan to make this available
Statistical Analysis Plan
No - There is not a plan to make this available
Informed Consent Form
No - There is not a plan to make this available
Clinical Study Report
Yes - There is a plan to make this available
Analytic Code
No - There is not a plan to make this available
Data Dictionary
No - There is not a plan to make this available
Title and more details about the data/document
Some of the data can potentially be shared after de-identification of individuals.
When the data will become available and for how long
The access period will begin 6 months after the publication of the results.
To whom data/document is available
All people
Under which criteria data/document could be used
Hospitals for clinical purposes and researchers for the accelerated advancement of projects.
From where data/document is obtainable
Scientific responsibility for the clinical trial: Stem Cell and Regenerative Medicine Research Center, Iran University of Medical Sciences, Shahid Motahari Hospital.
What processes are involved for a request to access data/document
A written request specifying the reasons for the need for the data.
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