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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

Phase 1
Completed
Conditions
Traumatic Brain Injury
Interventions
Registration Number
NCT04063215
Lead Sponsor
Hope Biosciences
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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
24
Inclusion Criteria
  1. adults between 18 and 55 years of age
  2. documented head injury with functional neurological damage to the central nervous system unlikely to improve with present standard of care approaches
  3. a Glasgow Outcome Scale-Extended (GOS-E) score > 2 and ≤ 6
  4. onset or diagnosis of the injury or disease process greater than 6 months
  5. ability to obtain consent from the subject of their legally authorized representative (LAR)
  6. ability to speak English or Spanish *required for validated neurocognitive outcome testing) -
Exclusion Criteria
  1. known history of:

    1. intellectual deficiency or psychiatric conditions likely to invalidate our ability to assess changes in cognition or behavior,
    2. recently treated infection,
    3. renal disease or altered renal function (screening serum creatinine > 1.5 mg/dL),
    4. hepatic disease or altered liver function (screening SGPT > 150 U/L or T. Bilirubin >1.3 mg/dL),
    5. cancer,
    6. immunosuppression (screening WBC < 3, 000 cells/ml),
    7. HIV+,
    8. chemical or ETOH dependency that in the opinion of the investigator would preclude participation in the study,
    9. acute or chronic lung disease requiring significant medication, oxygen supplementation, or mechanical ventilation,
    10. bleeding disorders including immune-mediated heparin-induced thrombocytopenia,
    11. known sensitivity to heparin, Lovenox, and pork products,
    12. individuals with mechanical prosthetic heart valves.
    13. individuals who have received a stem cell treatment.
  2. Normal brain CT/MRI exam

  3. Spinal deformity, spinal surgery (including repeated epidural or spinal punctures), or spinal cord injury diagnosed by CT/MR or clinical exam

  4. diagnosed with a genetic or metabolic disorder related to the neurologic condition

  5. other acute or chronic medical conditions that, in the opinion of the investigator, may increase the risks associated with study participation

  6. 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

  7. participation in a concurrent interventional study

  8. inability to undergo the diagnostic tests (PET/DT-MRI) or unwilling/unable to cooperate with the diagnostic tests and outcome assessments

  9. unwilling or unable to return for follow-up study visits -

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
HB-adMSCHB-adMSCsHB-adMSCs will be infused three times over a six week period, spaced 14 days apart
Primary Outcome Measures
NameTimeMethod
PotassiumScreening (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)

GlucoseScreening (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)

CreatinineScreening (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 phosphataseScreening (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)

CalciumScreening (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)

AlbuminScreening (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 ProteinScreening (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)

SodiumScreening (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 dioxideScreening (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)

ChlorideScreening (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)

Red blood cellScreening (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)

BUNScreening (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)

Aspartate aminotransferaseScreening (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 BilirubinScreening (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)

HemoglobinScreening (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)

Mean corpuscular hemoglobin concentrationScreening (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 widthScreening (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 (%)

Alanine aminotransferaseScreening (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)

HematocritScreening (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 volumeScreening (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)

LymphsScreening (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 (%)

MonocytesScreening (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 (%)

White blood cellScreening (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)

Mean corpuscular hemoglobinScreening (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)

NeutrophilsScreening (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 (%)

EosScreening (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 (%)

BasosScreening (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 NeutrophilsScreening (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)

Immature GranulocytesScreening (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 GranulocytesScreening (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)

Absolute LymphsScreening (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 monocytesScreening (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 EosScreening (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 BasosScreening (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)

PlateletsScreening (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 TimeScreening (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)

Urine PregnancyScreening (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)

INRScreening (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)

Secondary Outcome Measures
NameTimeMethod
Whole brain MRIBaseline, change from baseline at 6 months post-infusion

DTI to assess macro- and micro-structural properties

PET/DT-MRIBaseline, change from baseline at 6 months post-infusion

\[11C\]ER-176 tracer/label to identify brain proteins associated with neuroinflammatory response regulation

Glasgow Outcome ScoreBaseline, 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 TestBaseline, 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

TBI Quality of Life Questionnaires (TBI-QOL SF)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 MetricsBaseline, 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 TestBaseline, 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 TestBaseline, 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

StroopBaseline, 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-alphaBaseline, 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 4Baseline, 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 alphaBaseline, 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 6Baseline, 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 10Baseline, 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

AlbuminBaseline, change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion

measure concentration of albumin via BCG immunochemical analysis

Trial Locations

Locations (1)

Memorial Hermann Hospital-Clinical Research Unit (MMH-CRU)

🇺🇸

Houston, Texas, United States

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