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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Glucose [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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) [Срок оценки: 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 [Срок оценки: 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]

Вторичные конечные точки (12)

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

Критерии участия

Критерии включения

• 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).

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 2 центра

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

Идентификаторы

NCT: NCT05951777 · HBTBI02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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