A Clinical Trial to Determine the Safety and Efficacy of Hope Biosciences Autologous Mesenchymal Stem Cell Therapy for the Treatment of Traumatic Brain Injury and Hypoxic-Ischemic Encephalopathy

Study Overview
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Brief Summary
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This study aims to determine the safety of HB-adMSC infusion and treatment effects of HB-adMSC infusion on brain structure, neurocognitive/functional outcomes, and neuroinflammation after subacute and chronic neurological injury in adults.

Detailed Description
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This study aims to determine the safety of HB-adMSC infusion and treatment effects of HB-adMSC infusion on global gray and/or white matter, as well as structural integrity of GM and WM regions of interest in the corpus callous and corticospinal tracts as measured by fractional anisotropy (FA) and mean diffusivity (MD) in specific regions known to correlate with specific neurocognitive deficits in patients after neurological injury.

Official Title
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A Clinical Trial to Determine the Safety and Efficacy of Hope Biosciences Autologous Mesenchymal Stem Cell Therapy for the Treatment of Traumatic Brain Injury and Hypoxic-Ischemic Encephalopathy

Conditions
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Traumatic Brain Injury

Intervention / Treatment
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* Biological: HB-adMSCs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adults between 18 and 55 years of age documented head injury with functional neurological damage to the central nervous system unlikely to improve with present standard of care approaches a Glasgow Outcome Scale-Extended (GOS-E) score > 2 and ≤ 6 onset or diagnosis of the injury or disease process greater than 6 months ability to obtain consent from the subject of their legally authorized representative (LAR) ability to speak English or Spanish *required for validated neurocognitive outcome testing) - Exclusion Criteria: known history of: a) intellectual deficiency or psychiatric conditions likely to invalidate our ability to assess changes in cognition or behavior, b) recently treated infection, c) renal disease or altered renal function (screening serum creatinine > 1.5 mg/dL), d) hepatic disease or altered liver function (screening SGPT > 150 U/L or T. Bilirubin >1.3 mg/dL), e) cancer, f) immunosuppression (screening WBC < 3, 000 cells/ml), g) HIV+, h) chemical or ETOH dependency that in the opinion of the investigator would preclude participation in the study, i) acute or chronic lung disease requiring significant medication, oxygen supplementation, or mechanical ventilation, j) bleeding disorders including immune-mediated heparin-induced thrombocytopenia, k) known sensitivity to heparin, Lovenox, and pork products, l) individuals with mechanical prosthetic heart valves. Normal brain CT/MRI exam Spinal deformity, spinal surgery (including repeated epidural or spinal punctures), or spinal cord injury diagnosed by CT/MR or clinical exam diagnosed with a genetic or metabolic disorder related to the neurologic condition other acute or chronic medical conditions that, in the opinion of the investigator, may increase the risks associated with study participation for women of child bearing 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 participation in a concurrent interventional 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 -

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single arm, non-randomized study to determine safety and treatment effect of three infusions of HB-adMSC (2 x 10^8 total cells per dose) in adult patients with sub-acute or chronic neurological injury
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HB-adMSC<br>HB-adMSCs will be infused three times over a six week period, spaced 14 days apart | Biological: HB-adMSCs<br>* Hope Biosciences autologous adipose-derived mesenchymal stem cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose | clinical lab evaluation of level of glucose in the blood (mg/dL) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Calcium | clinical lab evaluation of level of calcium in the blood (mg/dL) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Albumin | clinical lab evaluation of level of albumin in the blood (g/dL) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Total Protein | clinical lab evaluation of total protein in the blood (g/dL) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Sodium | clinical lab evaluation of total sodium in the blood (mmol/L) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Total carbon dioxide | clinical lab evaluation of total carbon dioxide in the blood (mmol/L) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Potassium | clinical lab evaluation of potassium in the blood (mmol/L) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Chloride | clinical lab evaluation of chloride in the blood (mmol/L) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| BUN | clinical evaluation of blood urea nitrogen (BUN) (mg/dL) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Creatinine | clinical evaluation of creatinine in blood (mg/dL) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Alkaline phosphatase | clinical evaluation of alkaline phosphatase (ALP) in blood (IU/L) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Alanine aminotransferase | clinical evaluation of alanine aminotransferase (ALT) in blood (IU/L) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Aspartate aminotransferase | clinical evaluation of aspartate aminotransferase (AST) in blood (IU/L) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Total Bilirubin | clinical evaluation of total bilirubin in blood (mg/dL) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| White blood cell | clinical evaluation of white blood cells (WBC) in blood (x 10^3/uL) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Red blood cell | clinical evaluation of red blood cells (RBC) in blood (x 10^6/uL) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Hemoglobin | clinical evaluation of hemoglobin in blood (g/dL) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Hematocrit | clinical evaluation of hematocrit in blood (%) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Mean corpuscular volume | clinical evaluation of mean corpuscular volume (MCV) in blood (fL) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Mean corpuscular hemoglobin | clinical evaluation of mean corpuscular hemoglobin (MCH) in blood (pg) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Mean corpuscular hemoglobin concentration | clinical evaluation of mean corpuscular hemoglobin concentration (MCHC) in blood (g/dL) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Red cell distribution width | clinical evaluation of red cell distribution width (RDW) in blood (%) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Neutrophils | clinical evaluation of neutrophils in blood (%) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Lymphs | clinical evaluation of lymphocytes in blood (%) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Monocytes | clinical evaluation of monocytes in blood (%) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Eos | clinical evaluation of eosinophils in blood (%) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Basos | clinical evaluation of basophils in blood (%) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Absolute Neutrophils | clinical evaluation of absolute neutrophils in blood (x 10^3/uL) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Absolute Lymphs | clinical evaluation of absolute lymphocytes in blood (x 10^3/uL) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Absolute monocytes | clinical evaluation of absolute monocytes in blood (x 10^3/uL) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Absolute Eos | clinical evaluation of absolute eosinophils in blood (x 10^3/uL) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Absolute Basos | clinical evaluation of absolute basophils in blood (x 10^3/uL) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Immature Granulocytes | clinical evaluation of immature granulocytes in blood (%) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Absolute Immature Granulocytes | clinical evaluation of absolute immature granulocytes in blood (x 10^3/uL) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Platelets | clinical evaluation of platelets in blood (x 10^3/uL) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Prothrombin Time | clinical evaluation of time for blood to coagulate (seconds) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| INR | clinical evaluation of international normalized ratio of blood coagulation (no unit) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 
| Urine Pregnancy | clinical evaluation of human chorionic gonadotropin (hCG) in urine (positive/negative) | Screening (visit 1),change from screening at visit 3, change from screening at visit 4, change from screening at visit 5, change from screening at 6 months post-infusion (visit 6), change from screening at 1 year post-infusion (visit 7) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whole brain MRI | DTI to assess macro- and micro-structural properties | Baseline, change from baseline at 6 months post-infusion | 
| PET/DT-MRI | [11C]ER-176 tracer/label to identify brain proteins associated with neuroinflammatory response regulation | Baseline, change from baseline at 6 months post-infusion | 
| Glasgow Outcome Score | Dichotomized-Glasgow Outcomes Score (GOSE) to evaluate affect, functional outcome, and neuropsychological function | Baseline, change from baseline at Imaging visit #2, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion | 
| Galveston Orientation and Amnesia Test | Galveston Orientation and Amnesia Test (GOAT) evaluation of cognition | Baseline, change from baseline at Imaging visit #2, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion | 
| Rivermead Post-Concussion Symptoms Questionnaire | Rivermead Post-Concussion Symptoms Questionnaire (RPSQ) evaluation to identify presence and severity of concussive symptoms | Baseline, change from baseline at Imaging visit #2, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion | 
| Automated Neuropsychological Assessment Metrics | Automated Neuropsychological Assessment Metrics (ANAM) evaluation of attention, concentration, reaction time, memory, processing speed, and decision-making | Baseline, change from baseline at Imaging visit #2, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion | 
| Verbal Selective Reminding Test | Verbal Selective Reminding Test (VSRT) to evaluate verbal learning and memory | Baseline, change from baseline at Imaging visit #2, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion | 
| Verbal Fluency Test | Verbal Fluency Test (VFT) to evaluate vocabulary size, lexical access speed, updating, and inhibition ability | Baseline, change from baseline at Imaging visit #2, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion | 
| Stroop | Stroop to evaluate selective attention and cognitive flexibility | Baseline, change from baseline at Imaging visit #2, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion | 
| Interleukin 1-alpha | measure IL-1α via a bead-based, flow cytometric ELISA for the cytokines | Baseline, change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion | 
| Interleukin 4 | measure IL-4 via a bead-based, flow cytometric ELISA for the cytokines | Baseline, change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion | 
| Tumor necrosis factor alpha | measure TNFα via a bead-based, flow cytometric ELISA for the cytokines | Baseline, change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion | 
| Interleukin 6 | measure IL-6 via a bead-based, flow cytometric ELISA for the cytokines | Baseline, change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion | 
| Interleukin 10 | measure IL-10 via a bead-based, flow cytometric ELISA for the cytokines | Baseline, change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion | 
| Albumin | measure concentration of albumin via BCG immunochemical analysis | Baseline, change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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severe, hypoxic-ischemic encephalopathy, stroke, intracranial hemorrhage, cerebral palsy, chronic, neurological injury