Clinical trial NCT05951777: Autologous Adipose-Derived Mesenchymal Stem Cells for Chronic Traumatic Brain Injury
Official title: Autologous Adipose-Derived Mesenchymal Stem Cells for Chronic Traumatic Brain Injury
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Traumatic Brain Injury
Keywords: severe
intracranial hemorrhage
chronic
neurological injury
Lead sponsor: Hope Biosciences
Sponsor class: INDUSTRY
Collaborators: name: The University of Texas Health Science Center, Houston
First posted: 2023-07-19
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The global objective of this study is to establish the safety and investigate the potential treatment effect of an intravenous infusion of HB-adMSCs (Hope Biosciences adipose-derived mesenchymal stem cells) on brain structure, neurocognitive/functional outcomes, and neuroinflammation after traumatic brain injury.

Detailed description: This study is a prospective, randomized, double-blind, placebo-controlled Phase 2a study of three infusions of autologous HB-adMSCs (Hope Biosciences adipose-derived mesenchymal stem cells) (2 x 10\^8 total cells per dose) administered over a 6 week period with 14 day intervals between infusions. Subjects will be monitored and assessed for infusion related toxicity for at least 1 hour after the infusion and by telephone 24hr. after each infusion. Safety assessments will be conducted at the study follow-up clinic visits 6 and 12 months, and 2 years (telephone call) after the last HB-adMSC (Hope Biosciences adipose-derived mesenchymal stem cells) infusion, or more frequently if infusion related adverse events are suspected.

Eligibility criteria: Inclusion Criteria:

1. Adults between 18 and 55 years of age.
2. Documented functional neurological damage to the central nervous system from closed head trauma that is 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 and \< 20 years.
5. Ability to obtain consent from the subject or their legally authorized representative (LAR).
6. Ability to verbally communicate in 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, psychiatric conditions prior to TBI,
   2. recently treated infection,
   3. renal disease or altered renal function (screening eGFR \< 60 mL/min/1.73m2),
   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. Positive infectious disease tests including HIV, Hep. B, Hep. C., and Syphilis,
   8. chemical or ETOH dependency that in the opinion of the investigator would preclude enrollment,
   9. acute or chronic lung disease requiring significant medication/oxygen supplementation,
   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, gene or cellular therapy.
2. Normal brain CT/MRI exam.
3. History of spinal cord injury.
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 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.
7. Concurrent participation in interventional drug or device study.
8. Inability to undergo the diagnostic tests (PET/DT-MRI) or unwilling/unable to cooperate with the diagnostic tests and outcome assessments.
9. Metal implants including baclofen pumps that would preclude DT-MRI.
10. Unwilling or unable to return for the follow-up study visits.

Primary outcomes:
measure: Glucose
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Calcium
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Albumin
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Total Protein
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Sodium
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Total carbon dioxide
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Potassium
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Chloride
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: BUN (blood urea nitrogen)
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Creatinine
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Alkaline phosphatase
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Alanine aminotransferase
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Aspartate aminotransferase
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Total Bilirubin
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: White blood cell
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Red blood cell
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Hemoglobin
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Hematocrit
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Mean corpuscular volume
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Mean corpuscular hemoglobin
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Mean corpuscular hemoglobin concentration
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Red cell distribution width
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Neutrophils
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Lymphocytes
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Monocytes
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Eosinophils
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Basophils
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Absolute Neutrophils
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Absolute lymphocytes
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Absolute monocytes
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Absolute eosinophils
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Absolute basophils
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Immature Granulocytes
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Absolute Immature Granulocytes
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Platelets
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Prothrombin Time
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: INR (international normalized ratio)
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
measure: Urine Pregnancy (if applicable)
timeFrame: Week 0 (Infusion 1), change from week 0 (Infusion 1) at week 2 (Infusion 2), change from week 0 (Infusion 1) at week 4 (Infusion 3), change from week 0 (Infusion 1) at 6 months post-infusion, change from week 0 (Infusion 1) at 1 year post-infusion
Secondary outcomes:
measure: Whole brain MRI (Magnetic resonance imaging)
timeFrame: Baseline, change from baseline at 6 months post-infusion
measure: PET/DT-MRI (positron emission tomography/Diffusion tensor-Magnetic resonance imaging)
timeFrame: Baseline, change from baseline at 6 months post-infusion
measure: Glasgow Outcome Scale - Extended
timeFrame: Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
measure: Disability Rating Scale
timeFrame: Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
measure: Behavior Rating of Executive Functions-Adult
timeFrame: Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
measure: TBI (Traumatic Brain Injury) Quality of Life Questionnaires
timeFrame: Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
measure: Brief Symptom Inventory 18
timeFrame: Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
measure: NIH Toolbox - Pattern Comparison Processing Speed Test
timeFrame: Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
measure: NIH Toolbox - Dimensional Change Card Sort Test
timeFrame: Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
measure: NIH Toolbox - Picture Vocabulary Test
timeFrame: Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
measure: NIH Toolbox - List Sorting Working Memory Test
timeFrame: Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
measure: NIH Toolbox - Flanker Inhibitory Control and Attention Test
timeFrame: Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
measure: NIH Toolbox - 9-hole Pegboard Dexterity Test
timeFrame: Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
measure: Rey Auditory Verbal Learning Test
timeFrame: Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
measure: Verbal Fluency
timeFrame: Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
measure: Wechsler Adult Intelligence Scale - IV: Processing Speed Index
timeFrame: Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
measure: Plasma cytokines
timeFrame: Baseline imaging (visit #2), change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion
measure: Interleukin 1-alpha
timeFrame: Baseline imaging (visit #2), change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion
measure: Interleukin 4
timeFrame: Baseline imaging (visit #2), change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion
measure: Tumor necrosis factor alpha
timeFrame: Baseline imaging (visit #2), change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion
measure: Interleukin 6
timeFrame: Baseline imaging (visit #2), change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion
measure: Interleukin 10
timeFrame: Baseline imaging (visit #2), change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion
measure: Albumin
timeFrame: Baseline imaging (visit #2), change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion
Other outcomes:
Locations:
city: Houston,
country: United States
facility: Memorial Hermann Hospital / UTHealth McGovern Medical School at Houston
state: Texas
city: San Antonio
country: United States
facility: The University of Texas Health Science at San Antonio
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Charles S Cox, MD
role: PRINCIPAL_INVESTIGATOR
References: