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Efficacy of Intravenous Infusions of Stem Cells in the Treatment of COVID-19 Patients

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ClinicalTrials.gov Identifier: NCT04437823
Recruitment Status : Recruiting
First Posted : June 18, 2020
Last Update Posted : June 18, 2020
Sponsor:
Collaborator:
Johns Hopkins University
Information provided by (Responsible Party):
Prof. Sheikh Riazuddin, Jinnah Hospital

Tracking Information
First Submitted Date  ICMJE June 17, 2020
First Posted Date  ICMJE June 18, 2020
Last Update Posted Date June 18, 2020
Actual Study Start Date  ICMJE June 1, 2020
Estimated Primary Completion Date May 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 17, 2020)
  • Safety and efficacy assessment of infusion associated adverse events [ Time Frame: Day 01 to Day 30 ]
    Number of participants with significant side effects in stem cell treated group
  • Chest Radiograph or Chest CT Scan [ Time Frame: Day 01 to Day 30 ]
    Assessment of Pneumonia improvement as a result of stem cell infusions
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: June 17, 2020)
  • COVID-19 Quantitative Real Time PCR [ Time Frame: Day 01 to Day 30 ]
    Quantitative real-time PCR analysis for the evaluation of negative corona virus test results following stem cell treatment
  • Sequential Organ Failure Assessment (SOFA) Score [ Time Frame: Day 01 to Day 30 ]
    Evaluation of organ function (Each organ system is assigned a value for 0 (normal) to 4 (highest degree of dysfunction))
  • Rate of mortality [ Time Frame: Day 01 to Day 30 ]
    Number of all mortalities within 30 days post first infusion
  • Clinical Respiratory Changes [ Time Frame: Day 01 to Day 30 ]
    Examination of improvement in the physiology of lungs after treatment
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy of Intravenous Infusions of Stem Cells in the Treatment of COVID-19 Patients
Official Title  ICMJE Efficacy of Intravenous Infusions of Stem Cells in the Treatment of COVID-19 Patients
Brief Summary Stem cell therapy has emerged as a revolutionary treatment for diseases that were considered untreatable only a few years ago. Umbilical cord-derived mesenchymal stem cells (UCMSCs) have been shown to repair damaged liver, kidney, heart, pancreas, skin, cartilage, and cornea in animal models and several human trials. In addition to cellular replacement through regeneration, UCMSCs mediate through paracrine signaling pathways resulting in immune modulation. Clinical manifestations of coronavirus disease 2019 (COVID-19), are believed to arise from septic shock and cytokine storm that cause acute respiratory dysfunction and acute cardiac injury. There is presently no cure for the COVID-19 viral disease; however, multi-treatment strategies are being examined. During the past two months, four reports were published that suggest, mesenchymal stem cells (MSCs), owing to their powerful immunomodulatory ability, may prevent the cytokine storm and thus reduce the COVID-19 related morbidity. All studies reported that COVID-19 patients responded favorably to MSCs therapy. These reports, taken together with the previous successes of stem cell therapy in animal models, the investigators, a seven-institution consortium, propose to explore the efficacy of UCMSC treatment in COVID-19 patients at Jinnah hospital, Lahore. The investigators propose to administer UCMSCs in patients with acute pulmonary inflammation due to COVID-19 infection with moderate to severe symptoms. In the first cohort of 15 patients, UCMSCs will be administered with three intravenous infusions of 500,000 UCMSCs per Kg body weight each on days 1, 3, and 5. The second group of five patients serving as control will only receive standard treatment. During the 30-day post-infusion period, a battery of tests will be performed to evaluate the safety and efficacy of the UCMSCs treatment. In parallel, the investigators propose a comparative study to determine COVID-19 viral count by quantitative real-time PCR and through viral coat protein ELISA, developed in the investigator advisor lab (Dr. Tauseef Butt, Progenra Inc. Philadelphia, USA) with the ultimate objective to locally developing a rapid diagnostic assay.
Detailed Description Isolation and characterization of human umbilical cord-derived mesenchymal stem cells (UCMSCs): Human umbilical cord tissues along with informed consent forms will be collected from hepatitis B, C, and COVID-19 virus-negative women with healthy pregnancies during the Cesarean Section surgery after completion of gestation period. The cord tissue will be transported in sterile 1x phosphate-buffered saline (PBS) containing 200 units/ml penicillin and 200 µg/ml streptomycin on ice. In the biosafety cabinet, the cord will be washed with 4-5 changes of sterile 1x PBS and placed in a Petri plate with 15 ml PBS. The cord will be gently scraped with a surgical blade to remove any dead cells. A 9 cm umbilical cord will be cut into three equal pieces and wash thoroughly to remove blood clots, umbilical cord arteries, and veins. Segments will be washed three times with PBS and minced. The minced pieces will be incubated in 17.5 ml of collagenase solution (201 U/ml collagenase type I in serum-free DMEM-HG) in a 50 ml conical tube for ~3.5 hours in an incubator at 5% CO2, 95% humidity at 37⁰C. After ~3.5 hours, the digested lysate will pass through a strainer and will be diluted three times with 1x PBS. Following centrifugation, the cells will be seeded into two 25 cm2 flasks and will be placed in an incubator at 5% CO2, 95% humidity at 37⁰C. The flasks will be fed with fresh media (DMEM-HG supplemented with 20% FBS and 1% antibiotic solution) every third day. At around day 18, cells will reach up to 85% confluency and will be transferred in two 75 cm2 flasks with media replaced at alternate days. UCMSCs at P3 will be characterized using different specific antibodies. Cells at P3 will be used for transplantation in patients. Fifteen (15) subjects will be treated with three intravenous infusions (IV) of 500,000 UCMSCs per Kg body weight delivered via peripheral intravenous infusion.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Group 1 (15 subjects) Fifteen (15) subjects will be treated with three intravenous infusion (IV) of 5 x 10^5 (per Kg body weight) UCMSCs delivered via peripheral intravenous infusion on days 1, 3 and 5 besides the standard care (SOC).

Group 2 (5 subjects) Five (5) subjects will be treated under SOC. From two subjects in group 1 will not be treated 24hrs apart. Patients will be randomized in a 1:3 ratio (SOC: UCMSC).

Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Corona Virus Infection
Intervention  ICMJE Biological: Intravenous Infusions of Stem Cells
Cultured stem cells will be injected at days 1, 3 and 5 intravenously. While patients will be monitored and evaluated for various hematological and organ functions at baseline (day 0) and days 1, 3, 5, 7, 14, 21 and 30
Study Arms  ICMJE
  • Experimental: Group 1 : Treatment
    Fifteen (15) subjects will be treated with three intravenous infusion (IV) of 5 x 10^5 UCMSCs per Kg body weight delivered via peripheral intravenous infusion on days 1, 3 and 5 besides the standard care (SOC).
    Intervention: Biological: Intravenous Infusions of Stem Cells
  • No Intervention: Group 2: standard care
    Five (5) subjects will be treated under Standard of Care (SOC) .
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 17, 2020)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2021
Estimated Primary Completion Date May 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Provide written informed consent
  • Male or female subjects age >18 years at the time of signing the Informed Consent Form
  • Must have a clinical diagnosis of COVID-19, with at least one of clinical symptoms (e.g., fever ≥38°C, fatigue, cough) and a positive result by the reverse-transcription polymerase chain reaction (RT-PCR) testing or equivalent
  • Individuals with moderate to severe COVID-19 symptoms
  • Adequate venous access
  • For female patients only, willingness to use recommended birth control until 6 months post-treatment
  • Must agree to comply with all study requirements and be willing to complete all study visits
  • Need in-patient admission

Exclusion Criteria:

  • A female who is pregnant, nursing, or of child-bearing potential while not practicing effective contraceptive methods. Female subjects must undergo a blood pregnancy test at screening and prior to infusion.
  • Inability to perform any of the assessments required for endpoint analysis
  • Have known allergies to penicillin or streptomycin
  • Have a clinical history of malignancy within 3 years (i.e., subjects with prior malignancy must be disease-free for 3 years), except curatively-treated basal cell carcinoma, squamous cell carcinoma, melanoma in situ or cervical carcinoma, if recurrence occurs; - History of drug abuse (illegal "street" drugs except for marijuana, or prescription medications not being used appropriately for a pre-existing medical condition) or alcohol abuse (≥ 5 drinks/day for ˃ 3 months), or documented medical, occupational, or legal problems arising from the use of alcohol or drugs within the past 24 months
  • Be serum positive for HIV, hepatitis BsAg or Viremic hepatitis C.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sheikh Riazuddin, PhD +9242935164422 riazuddin@aimrc.org
Contact: Mohsin Shahzad, PhD +923218429448 riazuddin@aimrc.org
Listed Location Countries  ICMJE Pakistan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04437823
Other Study ID Numbers  ICMJE JB&RSC-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: The report will be published and available online.
Supporting Materials: Study Protocol
Supporting Materials: Clinical Study Report (CSR)
Time Frame: At the end of completion of the study
Access Criteria: Available online
Responsible Party Prof. Sheikh Riazuddin, Jinnah Hospital
Study Sponsor  ICMJE Jinnah Hospital
Collaborators  ICMJE Johns Hopkins University
Investigators  ICMJE
Principal Investigator: Moazzam N Tarar, MBBS, FCPS Jinnah Burn & Reconstructive Surgery Center, Lahore
Principal Investigator: Azra Mehmood, PhD Centre of Excellence in Molecular Biology, Lahore
PRS Account Jinnah Hospital
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP