Stem Cell Study for Long COVID-19 Neurological Symptoms

Study Overview
=================
Brief Summary
-----------------
The purpose of this research study is to test the safety and benefit of a human cord blood derived stem cell infusion as a treatment for individuals with post COVID-19 neurological problems. Participants in the study will have 6 clinic visits over a 12 to 14 mo. period with each visit lasting 2 to 6 hours. Participants will receive 1 stem cell infusion at study visit #3. Participants will have a brain PET and MRI scan at the baseline and 6mo. post-infusion visits. Follow-up safety assessments will be conducted at 6mo. and 1yr. after the stem cell infusion.

Detailed Description
-----------------
This is a non-randomized, Phase 1/2a dose escalation study using allogenic cord tissue MSC's in adults with chronic neurological symptoms following an acute COVID-19 infection.

Official Title
-----------------
Long COVID: Cord Tissue-Derived Mesenchymal Stromal Cells for Persistent NeuroInflammatory Symptoms

Conditions
-----------------
Post-Acute COVID-19 Syndrome

Intervention / Treatment
-----------------
* Biological: Stem Cell


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults between 18 and 55 years of age. Documented history of COVID-19 infection with resulting neurological sequela. Post-Covid-19 Functional Status score of grades 3 or 4. Chronic neurological symptoms defined as anxiety/depression, pain syndromes, sleep disorders, and /or memory disorders (brain fog) persisting 6 months after an acute COVID-19 infection. Ability to obtain consent from the subject. Ability to communicate in English or Spanish (required for validated neurocognitive outcome testing). Exclusion Criteria: Known history of: intellectual deficiency or psychiatric conditions likely to invalidate our ability to assess changes in cognition or behavior, recently treated infection, renal disease or altered renal function (screening serum creatinine > 1.5 mg/dL), hepatic disease or altered liver function (screening SGPT > 150 U/L and/or T. Bilirubin >1.3 mg/dL), cancer, immunosuppression (screening WBC < 3, 000 cells/ml), HIV+, chemical or ETOH dependency that in the opinion of the investigator would preclude participation in the study, acute or chronic lung disease requiring significant medication/oxygen supplementation, bleeding disorders including immune-mediated heparin-induced thrombocytopenia, hypercoagulable disorders (Protein C, S, ATIII deficiencies), Factor V Leiden, known sensitivity to heparin, Lovenox, and pork products, individuals with mechanical prosthetic heart valves. Pulse oximetry oxygen saturation <93% on room air. Other acute or chronic medical conditions that, in the opinion of the investigator, may increase the risks associated with study participation. For women of childbearing potential, a positive pregnancy test at the screening visit or, for both women and men, unwillingness to comply with acceptable methods of birth control during the study. Previous or concurrent participation in an interventional drug or biological study. Inability to undergo the diagnostic tests (PET/DT-MRI) or unwilling/unable to cooperate with the diagnostic tests and outcome assessments. Unwilling or unable to return for follow-up study visits. Prisoner/Incarcerated.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Non-Randomized, Phase 1/2a dose escalation using 4X10^6/kg, 6X10^6/kg and 8X10^6/kg and 10X10^10/kg cohorts of 3 patients using an adaptive Bayesian design based upon infusional toxicity/safety.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 4x10^6 Cells/kg Dose Group<br>This is a adaptive Baysian dose escalation study. The first 3 subjects will receive one stem cell infusion of 4x10^6 Cells/kg. If no infusion related AE/SAE are found, the next cohort will receive the next highest stem cell dose. | Biological: Stem Cell<br>* Stem cells derived from human cord tissue.<br>* Other names: Allogenic Human Cord Tissue Derived Mesenchymal Stromal Cells (hCTMSCs);|
| Experimental: 6x10^6 Cells/kg Dose Group<br>The next cohort of 3 subjects will receive one stem cell infusion of 6x10^6 Cells/kg. If no infusion related AE/SAE are found, the next cohort will receive the next highest stem cell dose. | Biological: Stem Cell<br>* Stem cells derived from human cord tissue.<br>* Other names: Allogenic Human Cord Tissue Derived Mesenchymal Stromal Cells (hCTMSCs);|
| Experimental: 8x10^6 Cells/kg Dose Group<br>The next cohort of 3 subjects will receive one stem cell infusion of 8x10^6 Cells/kg. If no infusion related AE/SAE are found, the next cohort will receive the next highest stem cell dose. | Biological: Stem Cell<br>* Stem cells derived from human cord tissue.<br>* Other names: Allogenic Human Cord Tissue Derived Mesenchymal Stromal Cells (hCTMSCs);|
| Experimental: 10x10^6 Cells/kg Dose Group<br>The last cohort of 3 subjects will receive one infusion of 10x10^6 Cells/kg. | Biological: Stem Cell<br>* Stem cells derived from human cord tissue.<br>* Other names: Allogenic Human Cord Tissue Derived Mesenchymal Stromal Cells (hCTMSCs);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the safety and establish the maximum tolerated dose (MTD) of allogenic human cord tissue derived MSCs (hCTMSCs) as determined by infusional toxicity of the cell product. | Physical Exam | Assessed for the first 24 hours after each stem cell infusion. | 
| Determine the safety and establish the maximum tolerated dose (MTD) of allogenic human cord tissue derived MSCs (hCTMSCs) as determined by infusional toxicity of the cell product. | Clinical Lab Assessments | Assessed for the first 24 hours after each stem cell infusion. | 
| Determine the safety and establish the maximum tolerated dose (MTD) of allogenic human cord tissue derived MSCs (hCTMSCs) as determined by infusional toxicity of the cell product. | Vital Signs | Assessed for the first 24 hours after each stem cell infusion. | 
| Determine the safety and establish the maximum tolerated dose (MTD) of allogenic human cord tissue derived MSCs (hCTMSCs) as determined by infusional toxicity of the cell product. | Subject Report of Adverse Event(s) | Assessed for the first 24 hours after each stem cell infusion. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigate if the hCTMSC infusions reduce the neuroinflammatory response following an acute COVID-19 infection as measured by the degree of microglial activation. | Comparison of Brain PET Scan at baseline visit and at 6 months post-infusion. | Baseline visit to 6 months post-infusion. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Post COVID-19 Neurological Injuries