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 Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: HB-adMSC HB-adMSCs will be infused three times over a six week period, spaced 14 days apart |
Biological: HB-adMSCs
Hope Biosciences autologous adipose-derived mesenchymal stem cells
|
Outcome Measures
Primary Outcome Measures
- Glucose [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)]
clinical lab evaluation of level of glucose in the blood (mg/dL)
- Calcium [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)]
clinical lab evaluation of level of calcium in the blood (mg/dL)
- Albumin [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)]
clinical lab evaluation of level of albumin in the blood (g/dL)
- Total Protein [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)]
clinical lab evaluation of total protein in the blood (g/dL)
- Sodium [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)]
clinical lab evaluation of total sodium in the blood (mmol/L)
- Total carbon dioxide [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)]
clinical lab evaluation of total carbon dioxide in the blood (mmol/L)
- Potassium [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)]
clinical lab evaluation of potassium in the blood (mmol/L)
- Chloride [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)]
clinical lab evaluation of chloride in the blood (mmol/L)
- BUN [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)]
clinical evaluation of blood urea nitrogen (BUN) (mg/dL)
- Creatinine [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)]
clinical evaluation of creatinine in blood (mg/dL)
- Alkaline phosphatase [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)]
clinical evaluation of alkaline phosphatase (ALP) in blood (IU/L)
- Alanine aminotransferase [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)]
clinical evaluation of alanine aminotransferase (ALT) in blood (IU/L)
- Aspartate aminotransferase [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)]
clinical evaluation of aspartate aminotransferase (AST) in blood (IU/L)
- Total Bilirubin [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)]
clinical evaluation of total bilirubin in blood (mg/dL)
- White blood cell [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)]
clinical evaluation of white blood cells (WBC) in blood (x 10^3/uL)
- Red blood cell [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)]
clinical evaluation of red blood cells (RBC) in blood (x 10^6/uL)
- Hemoglobin [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)]
clinical evaluation of hemoglobin in blood (g/dL)
- Hematocrit [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)]
clinical evaluation of hematocrit in blood (%)
- Mean corpuscular volume [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)]
clinical evaluation of mean corpuscular volume (MCV) in blood (fL)
- Mean corpuscular hemoglobin [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)]
clinical evaluation of mean corpuscular hemoglobin (MCH) in blood (pg)
- Mean corpuscular hemoglobin concentration [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)]
clinical evaluation of mean corpuscular hemoglobin concentration (MCHC) in blood (g/dL)
- Red cell distribution width [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)]
clinical evaluation of red cell distribution width (RDW) in blood (%)
- Neutrophils [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)]
clinical evaluation of neutrophils in blood (%)
- Lymphs [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)]
clinical evaluation of lymphocytes in blood (%)
- Monocytes [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)]
clinical evaluation of monocytes in blood (%)
- Eos [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)]
clinical evaluation of eosinophils in blood (%)
- Basos [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)]
clinical evaluation of basophils in blood (%)
- Absolute Neutrophils [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)]
clinical evaluation of absolute neutrophils in blood (x 10^3/uL)
- Absolute Lymphs [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)]
clinical evaluation of absolute lymphocytes in blood (x 10^3/uL)
- Absolute monocytes [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)]
clinical evaluation of absolute monocytes in blood (x 10^3/uL)
- Absolute Eos [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)]
clinical evaluation of absolute eosinophils in blood (x 10^3/uL)
- Absolute Basos [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)]
clinical evaluation of absolute basophils in blood (x 10^3/uL)
- Immature Granulocytes [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)]
clinical evaluation of immature granulocytes in blood (%)
- Absolute Immature Granulocytes [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)]
clinical evaluation of absolute immature granulocytes in blood (x 10^3/uL)
- Platelets [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)]
clinical evaluation of platelets in blood (x 10^3/uL)
- Prothrombin Time [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)]
clinical evaluation of time for blood to coagulate (seconds)
- INR [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)]
clinical evaluation of international normalized ratio of blood coagulation (no unit)
- Urine Pregnancy [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)]
clinical evaluation of human chorionic gonadotropin (hCG) in urine (positive/negative)
Secondary Outcome Measures
- Whole brain MRI [Baseline, change from baseline at 6 months post-infusion]
DTI to assess macro- and micro-structural properties
- PET/DT-MRI [Baseline, change from baseline at 6 months post-infusion]
[11C]ER-176 tracer/label to identify brain proteins associated with neuroinflammatory response regulation
- Glasgow Outcome Score [Baseline, change from baseline at Imaging visit #2, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion]
Dichotomized-Glasgow Outcomes Score (GOSE) to evaluate affect, functional outcome, and neuropsychological function
- Galveston Orientation and Amnesia Test [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 (GOAT) evaluation of cognition
- Rivermead Post-Concussion Symptoms Questionnaire [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 (RPSQ) evaluation to identify presence and severity of concussive symptoms
- Automated Neuropsychological Assessment Metrics [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 (ANAM) evaluation of attention, concentration, reaction time, memory, processing speed, and decision-making
- Verbal Selective Reminding Test [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 (VSRT) to evaluate verbal learning and memory
- Verbal Fluency Test [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 (VFT) to evaluate vocabulary size, lexical access speed, updating, and inhibition ability
- Stroop [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 to evaluate selective attention and cognitive flexibility
- Interleukin 1-alpha [Baseline, change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion]
measure IL-1α via a bead-based, flow cytometric ELISA for the cytokines
- Interleukin 4 [Baseline, change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion]
measure IL-4 via a bead-based, flow cytometric ELISA for the cytokines
- Tumor necrosis factor alpha [Baseline, change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion]
measure TNFα via a bead-based, flow cytometric ELISA for the cytokines
- Interleukin 6 [Baseline, change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion]
measure IL-6 via a bead-based, flow cytometric ELISA for the cytokines
- Interleukin 10 [Baseline, change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion]
measure IL-10 via a bead-based, flow cytometric ELISA for the cytokines
- Albumin [Baseline, change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion]
measure concentration of albumin via BCG immunochemical analysis
Eligibility Criteria
Criteria
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:
- 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 -
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Memorial Hermann Hospital-Clinical Research Unit (MMH-CRU) | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Hope Biosciences
- The University of Texas Health Science Center, Houston
Investigators
- Principal Investigator: Charles S Cox, MD, The University of Texas Health Science Center, Houston
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HBTBI01