Autologous Adipose-Derived Mesenchymal Stem Cells for Chronic Traumatic Brain Injury

Overview

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.

Interventions

• Biological Autologous HB-adMSCs
  Hope Biosciences autologous adipose-derived mesenchymal stem cells
• Drug Normal Saline
  Sterile Saline Solution 0.9%

Primary outcome measures

• Glucose [Time frame: 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]
• Calcium [Time frame: 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]
• Albumin [Time frame: 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]
• Total Protein [Time frame: 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]
• Sodium [Time frame: 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]
• Total carbon dioxide [Time frame: 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]
• Potassium [Time frame: 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]
• Chloride [Time frame: 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]
• BUN (blood urea nitrogen) [Time frame: 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]
• Creatinine [Time frame: 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 outcome measures (12)

• Whole brain MRI (Magnetic resonance imaging) [Time frame: Baseline, change from baseline at 6 months post-infusion]
• PET/DT-MRI (positron emission tomography/Diffusion tensor-Magnetic resonance imaging) [Time frame: Baseline, change from baseline at 6 months post-infusion]
• Glasgow Outcome Scale - Extended [Time frame: Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion]
• Disability Rating Scale [Time frame: Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion]
• Behavior Rating of Executive Functions-Adult [Time frame: Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion]
• TBI (Traumatic Brain Injury) Quality of Life Questionnaires [Time frame: Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion]
• Brief Symptom Inventory 18 [Time frame: Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion]
• NIH Toolbox - Pattern Comparison Processing Speed Test [Time frame: Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion]
• NIH Toolbox - Dimensional Change Card Sort Test [Time frame: Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion]
• NIH Toolbox - Picture Vocabulary Test [Time frame: Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion]
• NIH Toolbox - List Sorting Working Memory Test [Time frame: Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion]
• NIH Toolbox - Flanker Inhibitory Control and Attention Test [Time frame: Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion]

Eligibility criteria

Inclusion criteria

• Adults between 18 and 55 years of age.
• Documented functional neurological damage to the central nervous system from blunt force head trauma 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 and ≤ 20 years.
• Ability to obtain consent from the subject or their legally authorized representative (LAR).
• Ability to verbally communicate in English or Spanish (required for validated neurocognitive outcome testing).

Exclusion criteria

• Known history of:

• intellectual deficiency or uncontrolled psychiatric conditions likely to invalidate our ability to assess changes in cognition or behavior, or at the discretion of the PI,
• recently treated infection,
• renal disease or altered renal function (screening eGFR < 60 mL/min/1.73m2),
• hepatic disease or altered liver function (screening SGPT > 150 U/L or T. Bilirubin >1.3 mg/dL),
• cancer,
• immunosuppression (screening WBC < 3, 000 cells/ml),
• Positive infectious disease tests including HIV, Hep. B, Hep. C., and Syphilis,
• chemical or ETOH dependency that in the opinion of the investigator would preclude enrollment/participation in the study,
• acute or chronic lung disease requiring significant medication/oxygen supplementation,
• bleeding disorders, thrombocytopenia, including immune-mediated heparin-induced thrombocytopenia,
• known sensitivity to heparin, Lovenox, and pork products,
• individuals with mechanical prosthetic heart valves,
• individuals who have received a stem cell treatment, gene or cellular therapy.
• Normal brain CT/MRI exam.
• Planned epidural or spinal anesthesia, or undergoing spinal puncture, complete spinal cord injury.
• 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 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 during the study.
• Concurrent participation in interventional drug or device study.
• Inability to undergo the diagnostic tests (PET/DT-MRI) or unwilling/unable to cooperate with the diagnostic tests and outcome assessments.
• Metal implants including baclofen pumps that would preclude DT-MRI.
• Unwilling or unable to return for the follow-up study visits.
• Uncorrectable vision impairment that will prevent completion of neurocognitive tests require visual processing.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 2 centers

• Memorial Hermann Hospital / UTHealth McGovern Medical School at Houston — Houston
• The University of Texas Health Science at San Antonio — San Antonio

Identifiers

NCT: NCT05951777 · HBTBI02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗