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

• ClinicalTrials.gov Identifier: NCT04063215
• Recruitment Status: Recruiting
• First Posted: August 21, 2019
• Last Update Posted: May 6, 2022
• Sponsor: Hope Biosciences
• Collaborator: The University of Texas Health Science Center, Houston
• Information provided by (Responsible Party): Hope Biosciences

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
Traumatic Brain Injury	Biological: HB-adMSCs	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

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention 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)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: January 1, 2020
• Estimated Primary Completion Date: August 29, 2024
• Estimated Study Completion Date: August 29, 2024

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 :

1. Glucose [ Time Frame: 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)
2. Calcium [ Time Frame: 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)
3. Albumin [ Time Frame: 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)
4. Total Protein [ Time Frame: 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)
5. Sodium [ Time Frame: 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)
6. Total carbon dioxide [ Time Frame: 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)
7. Potassium [ Time Frame: 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)
8. Chloride [ Time Frame: 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)
9. BUN [ Time Frame: 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)
10. Creatinine [ Time Frame: 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)
11. Alkaline phosphatase [ Time Frame: 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)
12. Alanine aminotransferase [ Time Frame: 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)
13. Aspartate aminotransferase [ Time Frame: 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)
14. Total Bilirubin [ Time Frame: 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)
15. White blood cell [ Time Frame: 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)
16. Red blood cell [ Time Frame: 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)
17. Hemoglobin [ Time Frame: 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)
18. Hematocrit [ Time Frame: 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 (%)
19. Mean corpuscular volume [ Time Frame: 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)
20. Mean corpuscular hemoglobin [ Time Frame: 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)
21. Mean corpuscular hemoglobin concentration [ Time Frame: 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)
22. Red cell distribution width [ Time Frame: 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 (%)
23. Neutrophils [ Time Frame: 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 (%)
24. Lymphs [ Time Frame: 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 (%)
25. Monocytes [ Time Frame: 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 (%)
26. Eos [ Time Frame: 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 (%)
27. Basos [ Time Frame: 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 (%)
28. Absolute Neutrophils [ Time Frame: 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)
29. Absolute Lymphs [ Time Frame: 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)
30. Absolute monocytes [ Time Frame: 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)
31. Absolute Eos [ Time Frame: 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)
32. Absolute Basos [ Time Frame: 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)
33. Immature Granulocytes [ Time Frame: 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 (%)
34. Absolute Immature Granulocytes [ Time Frame: 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)
35. Platelets [ Time Frame: 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)
36. Prothrombin Time [ Time Frame: 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)
37. INR [ Time Frame: 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)
38. Urine Pregnancy [ Time Frame: 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 :

1. Whole brain MRI [ Time Frame: Baseline, change from baseline at 6 months post-infusion ]
   DTI to assess macro- and micro-structural properties
2. PET/DT-MRI [ Time Frame: Baseline, change from baseline at 6 months post-infusion ]
   [11C]ER-176 tracer/label to identify brain proteins associated with neuroinflammatory response regulation
3. Glasgow Outcome Score [ Time Frame: 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
4. Galveston Orientation and Amnesia Test [ Time Frame: 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
5. Rivermead Post-Concussion Symptoms Questionnaire [ Time Frame: 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
6. Automated Neuropsychological Assessment Metrics [ Time Frame: 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
7. Verbal Selective Reminding Test [ Time Frame: 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
8. Verbal Fluency Test [ Time Frame: 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
9. Stroop [ Time Frame: 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
10. Interleukin 1-alpha [ Time Frame: 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
11. Interleukin 4 [ Time Frame: 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
12. Tumor necrosis factor alpha [ Time Frame: 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
13. Interleukin 6 [ Time Frame: 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
14. Interleukin 10 [ Time Frame: 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
15. Albumin [ Time Frame: 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

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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:

   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.

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 -

Contacts and Locations

Contacts

Contact: Steven Kosmach, MSN; 713-500-7329; steven.kosmach@uth.tmc.edu

Contact: Joiya Arrington, MSN; 713-500-7395; joiya.arrington@uth.tmc.edu

Locations

United States, Texas

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

Houston, Texas, United States, 77030

Contact: Steven Kosmach, MSN 713-500-7329 Steven.Kosmach@uth.tmc.edu

Contact: Joiya Arrington, MSN (713) 500-7395 Joiya.Arrington@uth.tmc.edu

Principal Investigator: Charles S Cox, MD

Sub-Investigator: Sean S Savitz, MD

Sub-Investigator: Alan Prossin, MD

Sub-Investigator: Jennifer Juranek, PhD

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

More Information

• Responsible Party: Hope Biosciences
• ClinicalTrials.gov Identifier: NCT04063215
• Other Study ID Numbers: HBTBI01
• First Posted: August 21, 2019
• Last Update Posted: May 6, 2022
• Last Verified: April 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hope Biosciences:

severe; hypoxic-ischemic encephalopathy; stroke; intracranial hemorrhage; cerebral palsy; chronic; neurological injury

Additional relevant MeSH terms:

Brain Injuries; Brain Injuries, Traumatic; Brain Diseases; Brain Ischemia; Hypoxia-Ischemia, Brain; Wounds and Injuries; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Hypoxia; Signs and Symptoms, Respiratory; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Hypoxia, Brain