Mesenchymal Stem Cell Infusion for COVID-19 Infection

Sponsor

Dr. Zaineb Akram (Other)

Overall Status

Unknown status

CT.gov ID

NCT04444271

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Since the outbreak of coronavirusdisease2019(COVID-19), many researchers in China have carried out/published clinical trials on treatment based on Western medicine, traditional Chinese medicine or a combination of the two. Trials on treatment modalities have mainly used antivirals, interferon, glucocorticoids in addition to traditional Chinese medicine. There are also clinical trials exploring hydroxyquinoline/chloroquine sulphate, immunoglobulins, Vitamin-C, washed microbiota, nebulized interferon, teicoplanin as well as Mesenchymal stem cells. However, most of these trials were small (median sample size 100) and the bulk of potential therapeutic strategies remain in the experimental phase and currently there is no eﬀective speciﬁc antiviral with high-level evidence.The aim of this study is assess the efficacy of MSCs as an add-on therapy to standard supportive treatment for patients with moderate/severe COVID-19.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Drug: Mesenchymal stem cells Other: Placebo	Phase 2

Detailed Description

All patients will receive 2x10^{6 cells/kg on days 1 and day 7 (if needed). The study will be
divided in 2 phases. In the first phase, 10 patients will be included and randomized to 2
groups (5 Treatment arm; 5 Control Arm) and receive 2 x10}6 cells/kg MSCs on days 1 and 7 in addition to standard care. Thereafter, the trial committee will meet and evaluate all collected safety and efficacy information to decide about crossover of Control arm to treatment arm if patient deteriorates clinically while in Control arm. Then, 10 new subjects will be included in the study and treated according to protocol.

Preparation of MSCs doses MSCs will be isolated from bone marrow harvested cells. About 50ml bone marrow will be collected from iliac crest using aseptic technique in syringes primed with anticoagulant. The collected sample will be diluted with Phosphate Buffer Saline (PBS) and MSCs will be separated using density gradient centrifugation. After resuspension the cells will be seeded at a fixed concentration of 100,000 cells/cm2 in specially designed flasks and incubated at 37oC in 5% carbondioxide (CO2). Medium will be changed after every third day till harvesting of MSCs from the flasks. Once confluent (approximately day 20) the cells will be harvested with sterile techniques using Trypsin- Ethylenediaminetetraacetic acid ( EDTA ) solution. The prepared cells can either be stored in 50ml cryogenic vials for future use or infused immediately.

Patient Selection and MSCs demand Patient for MSCs and Control arm will be selected by multidisciplinary team (MDT) comprising Critical Care Specialist, Pulmonologist, Infectious Disease Specialist, Clinical Hematologist.

Demand for MSCs will be initiated on pre-designated forms , signed by Critical care Specialist Clearly indicating indication of MSCs.
Request form will be sent Stem Cell Lab.
Incharge stem Cell Lab will authorize issuance of the MSCs dose.
Stem Cell Lab will issue the dose Administration of MSCs
Experimental arm: Frozen MSCs will be resuspended in 100ml normal saline for immediate use and given intravenously. The patients should be pre-medicated to avoid allergic reactions to third party MSCs. Each patient in Experimental arm will be given 2 x 106 cells/kg will be administered on day 1,7 in addition to supportive care 2. Control Arm: Will be Continued on supportive care

Proposed usage:

Because of the very limited availability of MSCs, their usage has to be rationalized by MDT comprising of pulmonologist, critical care specialist and clinical haematologist and Infectious disease specialist.There is not enough evidence to put forth therapeutic recommendations however, treatment decisions can be made on case to case basis after MDT.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Prospective, Randomized Phase 2 Clinical Trial of Mesenchymal Stem Cells(MSCs) for the Treatment of Coronavirus Disease 2019(COVID-19)

Actual Study Start Date :

May 1, 2020

Anticipated Primary Completion Date :

Aug 30, 2020

Anticipated Study Completion Date :

Sep 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mesenchymal stem cells 10 patients will be given mesenchymal stem cells at dose 2x10^6 cells/kg MSCs on days 1 and day 7 (if needed) in addition to standard care	Drug: Mesenchymal stem cells 1. Frozen MSCs will be resuspended in 100ml normal saline for immediate use and given intravenously. The patients should be pre-medicated to avoid allergic reactions to third party MSCs. Each patient in Experimental arm will be given 2 x 106 cells/kg will be administered on day 1,7 in addition to supportive care Other Names: MSCs
Placebo Comparator: Placebo Only supportive care will be given to 10 patients	Other: Placebo 100 ml of normal saline will be given intravenously to control arm

Arm

Intervention/Treatment

Experimental: Mesenchymal stem cells

10 patients will be given mesenchymal stem cells at dose 2x10^6 cells/kg MSCs on days 1 and day 7 (if needed) in addition to standard care

Drug: Mesenchymal stem cells

1. Frozen MSCs will be resuspended in 100ml normal saline for immediate use and given intravenously. The patients should be pre-medicated to avoid allergic reactions to third party MSCs. Each patient in Experimental arm will be given 2 x 106 cells/kg will be administered on day 1,7 in addition to supportive care

Other Names:

MSCs

Placebo Comparator: Placebo

Only supportive care will be given to 10 patients

Other: Placebo

100 ml of normal saline will be given intravenously to control arm

Outcome Measures

Primary Outcome Measures

Overall survival [30 days post intervention]
Assessment of Overall survival at 30 days post intervention

Secondary Outcome Measures

Clinical improvement [30 days]
days required for oxygen support independence after intervention
Time of COVID19 PCR negativity [day 1,3,7,10, 14]
PCR testing to check PCR negativity
Radiological improvement (day 15 and day 30 assessment) [day 15 and day30]
Computed tomography Chest assesment will be done to assess improvment in radiological findings of COVID-19
days required to discharge from hospital [30 days post admission]
number of days required for discharge from hospital

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female, aged ≥ 10years
Laboratory confirmation of COVID19 infection by reverse-transcription polymerase chain reaction (RT-PCR) from any diagnostic sampling source; and
Moderate illness: In compliance with the 2019-coronavirus pneumonia diagnosis standard [according to the novel coronavirus infection pneumonia diagnosis and treatment program (Trial Implementation Version 6) issued by the National Health and Medical Commission, and world health organization (WHO) 2019 new coronavirus guidelines standards]: (A) increased breathing rate (≥30 beats / min), difficulty breathing, cyanosis of the lips; (B) in resting state, means oxygen saturation ≤93%; (C) partial pressure of arterial oxygen (PaO2) / Fraction of inspired oxygen (FiO2) ≤300 mmHg (1mmHg = 0.133kPa);
Critically ill : Respiratory failure, Septic Shock, muti-organ dysfunction syndrome (MODS)

Exclusion Criteria:

Patients with systemic autoimmune diseases
Not consenting for clinical trial
Those declared not for resuscitation due to underlying comorbid or current critical condition

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	NIBMT	Rawalpindi	Punjab	Pakistan	46000

Sponsors and Collaborators

Dr. Zaineb Akram

Investigators

Study Chair: xanab akram, NIBMT

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Dr. Zaineb Akram, Research officer, National Institute of Blood and Marrow Transplant (NIBMT), Pakistan

ClinicalTrials.gov Identifier:

NCT04444271

Other Study ID Numbers:

NIBMT-MSc-COVID-2020

First Posted:

Jun 23, 2020

Last Update Posted:

Jun 30, 2020

Last Verified:

Jun 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Dr. Zaineb Akram, Research officer, National Institute of Blood and Marrow Transplant (NIBMT), Pakistan

Coronavirus

Mesenchymal Stem Cells

Survival

Additional relevant MeSH terms:

COVID-19

Study Results

No Results Posted as of Jun 30, 2020