search
Back to results

Autologous Adipose Derived Mesenchymal Stem Cells for Chronic Traumatic Brain Injury

Primary Purpose

Traumatic Brain Injury

Status
Not yet recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Autologous HB-adMSCs
Normal Saline
Sponsored by
Hope Biosciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Traumatic Brain Injury focused on measuring severe, hypoxic-ischemic encephalopathy, intracranial hemorrhage, cerebral palsy, chronic, neurological injury

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Adults between 18 and 55 years of age. Documented functional neurological damage to the central nervous system from closed head trauma that is 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. Ability to obtain consent from the subject or their legally authorized representative (LAR). Ability to communicate in English or Spanish (required for validated neurocognitive outcome testing). Exclusion Criteria: 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 eGFR (estimated glomerular filtration rate) > 60 mL/min/1.73m2); d) hepatic disease or altered liver function (screening SGPT (serum glutamate pyruvate transaminase) > 150 U/L or T. Bilirubin >1.3 mg/dL); e) cancer; f) immunosuppression (screening WBC (white blood cell) < 3, 000 cells/ml); g) HIV+ (human immunodeficiency virus positive); h) chemical or ETOH (Ethanol/Alcohol) 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; 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; m) individuals who have received a stem cell treatment. Normal brain CT/MRI (computed tomography/magnetic resonance imaging) exam. Spinal deformity, spinal surgery (including repeated epidural or spinal punctures), or complete spinal cord injury diagnosed by CT (computed tomography) or MR (magnetic resonance) imaging or by clinical findings. 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 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. Concurrent participation in interventional drug or device study. Inability to undergo the diagnostic tests (PET/DT-MRI (positron emission tomography/diffusion tensor-magnetic resonance imaging)) or unwilling/unable to cooperate with the diagnostic tests and outcome assessments. Metal implants including baclofen pumps that would preclude DT-MRI (Diffusion tensor-magnetic resonance imaging). Unwilling or unable to return for the follow-up study visits.

Sites / Locations

  • Memorial Hermann Hospital / UTHealth McGovern Medical School at Houston
  • Audie Murphy VA Hospital, Bartter Research Unit

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Treatment

Placebo

Arm Description

Autologous Adipose Derived Mesenchymal Stem Cells

Normal Saline

Outcomes

Primary Outcome Measures

Glucose
clinical lab evaluation of level of glucose in the blood (mg/dL)
Calcium
clinical lab evaluation of level of calcium in the blood (mg/dL) clinical lab evaluation of level of calcium in the blood (mg/dL) clinical lab evaluation of level of calcium in the blood (mg/dL)
Albumin
clinical lab evaluation of level of albumin in the blood (g/dL)
Total Protein
clinical lab evaluation of total protein in the blood (g/dL)
Sodium
clinical lab evaluation of total sodium in the blood (mmol/L)
Total carbon dioxide
clinical lab evaluation of total carbon dioxide in the blood (mmol/L)
Potassium
clinical lab evaluation of potassium in the blood (mmol/L)
Chloride
clinical lab evaluation of chloride in the blood (mmol/L)
BUN (blood urea nitrogen)
clinical evaluation of blood urea nitrogen (BUN) (mg/dL)
Creatinine
clinical evaluation of creatinine in blood (mg/dL
Alkaline phosphatase
clinical evaluation of alkaline phosphatase (ALP) in blood (IU/L)
Alanine aminotransferase
clinical evaluation of alanine aminotransferase (ALT) in blood (IU/L)
Aspartate aminotransferase
clinical evaluation of aspartate aminotransferase (AST) in blood (IU/L)
Total Bilirubin
clinical evaluation of total bilirubin in blood (mg/dL)
White blood cell
clinical evaluation of white blood cells (WBC) in blood (x 10^3/uL)
Red blood cell
clinical evaluation of red blood cells (RBC) in blood (x 10^6/uL)
Hemoglobin
clinical evaluation of hemoglobin in blood (g/dL)
Hematocrit
clinical evaluation of hematocrit in blood (%)
Mean corpuscular volume
clinical evaluation of mean corpuscular volume (MCV) in blood (fL)
Mean corpuscular hemoglobin
clinical evaluation of mean corpuscular hemoglobin (MCH) in blood (pg)
Mean corpuscular hemoglobin concentration
clinical evaluation of mean corpuscular hemoglobin concentration (MCHC) in blood (g/dL)
Red cell distribution width
clinical evaluation of red cell distribution width (RDW) in blood (%)
Neutrophils
clinical evaluation of neutrophils in blood (%)
Lymphocytes
clinical evaluation of lymphocytes in blood (%)
Monocytes
clinical evaluation of monocytes in blood (%)
Eosinophils
clinical evaluation of eosinophils in blood (%)
Basophils
clinical evaluation of basophils in blood (%)
Absolute Neutrophils
clinical evaluation of absolute neutrophils in blood (x 10^3/uL)
Absolute lymphocytes
clinical evaluation of absolute lymphocytes in blood (x 10^3/uL)
Absolute monocytes
clinical evaluation of absolute monocytes in blood (x 10^3/uL)
Absolute eosinophils
clinical evaluation of absolute eosinophils in blood (x 10^3/uL)
Absolute basophils
clinical evaluation of absolute basophils in blood (x 10^3/uL)
Immature Granulocytes
clinical evaluation of immature granulocytes in blood (%)
Absolute Immature Granulocytes
clinical evaluation of absolute immature granulocytes in blood (x 10^3/uL)
Platelets
clinical evaluation of platelets in blood (x 10^3/uL)
Prothrombin Time
clinical evaluation of time for blood to coagulate (seconds)
INR (international normalized ratio)
clinical evaluation of international normalized ratio of blood coagulation (no unit)
Urine Pregnancy (if applicable)
clinical evaluation of human chorionic gonadotropin (hCG) in urine (positive/negative)

Secondary Outcome Measures

Whole brain MRI (Magnetic resonance imaging)
DTI (Diffusion tensor imaging) to assess macro- and micro-structural properties
PET/DT-MRI (positron emission tomography/Diffusion tensor-Magnetic resonance imaging)
[11C]ER-176 (a Radioligand for 18-kDa (Translocator Protein)) tracer/label to identify brain proteins associated with neuroinflammatory response regulation
Glasgow Outcome Scale - Extended
Dichotomized-Glasgow Outcomes Score (GOSE) to evaluate affect, functional outcome, and neuropsychological function. Minimum score = 1 = dead; 2 = vegetative state; 3 = lower severe disability; 4 = upper severe disability; 5 = lower moderate disability; 6 = upper moderate disability; 7 = lower good recovery; Maximum score = 8 = upper good recovery; Higher scores indicate better outcome.
Brain Injury Functional Outcome Measure
High precision global functioning measure providing extended range and responsivity to change
Behavior Rating of Executive Functions-Adult
Behavior Regulation and Metacognitive Indices assess everyday executive functions
TBI (Traumatic Brain Injury) Quality of Life Questionnaires
TBI-QOL SF (Traumatic Brain Injury-Quality of Life Short-Form) measures physical, psychological health, cognitive, and participation outcomes: Cognition: minimum raw score = 10, maximum raw score = 50. A higher score represents better functioning. Communication/Comprehension: minimum raw score = 9, maximum raw score = 45. A higher score represents better functioning. Independence: minimum raw score = 8, maximum raw score = 40. A higher score represents better functioning. Mobility: minimum raw score = 9, maximum raw score = 45. A higher score represents better functioning. Satisfaction with Social Roles & Activities: minimum raw score = 10, maximum raw score = 50. A higher score represents better functioning. Upper Extremity Function: minimum raw score = 9, maximum raw score = 45. A higher score represents better functioning.
Brief Symptom Inventory 18
Brief Symptom Inventory with 18 items contains three six-item scales for somatization, anxiety, depression, and the global Scale Global Severity Index (GSI). Each item is scored either 0 (Not at all), 1 (A little bit), 2 (Moderately), 3 (Quite a bit), 4 (Extremely), or R (Refused). The GSI therefore ranges between 0 (minimum) - 72 (maximum) and the three scales range between 0 (minimum) - 24 (maximum). Higher scores indicate worse outcome.
NIH Toolbox - Pattern Comparison Processing Speed Test
An assessment of processing speed. Participants are asked to quickly determine whether two stimuli are the same or not the same. Participants are measured based on reaction time (seconds) and accuracy.
NIH Toolbox - Dimensional Change Card Sort Test
An assessment of cognitive flexibility and attention. Participants are asked to match a series of bivalent test pictures (e.g., yellow balls and blue trucks) to the target pictures, first according to one dimension (e.g., color) and then, after a number of trials, according to the other dimension (e.g., shape). Participants are measured based on reaction time (seconds) and accuracy.
NIH Toolbox - Picture Vocabulary Test
An assessment of receptive vocabulary administered in a computer-adaptive test (CAT) format. Participants must choose which of four pictures best represents a word presented via audio. Participants are measured based on reaction time (seconds) and accuracy.
NIH Toolbox - List Sorting Working Memory Test
Designed to assess working memory (WM). List Sorting is a sequencing task requiring participants to sort and sequence stimuli that are presented visually and auditorily. Participants are measured based on accuracy.
NIH Toolbox - Flanker Inhibitory Control and Attention Test
An assessment of inhibitory control and attention. The participant is asked to focus on a particular stimulus while inhibiting attention to the stimuli flanking it. Participants are measured based on reaction time (seconds) and accuracy.
NIH Toolbox - 9-hole Pegboard Dexterity Test
The NIH Toolbox 9-Hole Pegboard Dexterity Test is a simple test of manual dexterity; it records the time required for the participant to accurately place and remove nine plastic pegs into a plastic pegboard. Raw scores are recorded as time in seconds that it takes the participant to complete the task with each hand (a separate score for each - Dominant vs. Non-Dominant Hand). Shorter time to complete the task indicates a better outcome. Longer time to complete the task indicates a worse outcome.
Rey Auditory Verbal Learning Test
Immediate learning and delayed recall of a word list
Verbal Fluency
Attentional control and verbal generativity
Wechsler Adult Intelligence Scale - IV: Processing Speed Index
Information processing rate on paper-pencil tasks requiring visual attention. It is composed of 10 core subtests and five supplemental subtests, with the 10 core subtests comprising the Full Scale IQ. There are four index scores representing major components of intelligence: Verbal Comprehension Index (VCI); Perceptual Reasoning Index (PRI); Working Memory Index (WMI); Processing Speed Index (PSI) Two broad scores are also generated, which can be used to summarize general intellectual abilities: Full Scale IQ (FSIQ), based on the total combined performance of the VCI, PRI, WMI, and PSI; General Ability Index (GAI), based only on the six subtests that comprise the VCI and PRI The range of possible WAIS-IV (Wechsler Adult Intelligence Scale - IV) full scale IQs is 45-155. The WAIS-IV computes scaled scores for each individual based exclusively on chronological age. Higher score indicates better outcome.
Plasma cytokines
measure plasma cytokines via a bead-based, flow cytometric ELISA (enzyme-linked immunosorbent assay) for the cytokines
Interleukin 1-alpha
measure IL-1α (Interleukin 1-alpha) via a bead-based, flow cytometric ELISA (enzyme-linked immunosorbent assay) for the cytokines
Interleukin 4
measure IL-4 (Interleukin 4) via a bead-based, flow cytometric ELISA (enzyme-linked immunosorbent assay) for the cytokines
Tumor necrosis factor alpha
measure TNFα (Tumor necrosis factor alpha) via a bead-based, flow cytometric ELISA (enzyme-linked immunosorbent assay) for the cytokines
Interleukin 6
measure IL-6 via a bead-based, flow cytometric ELISA (enzyme-linked immunosorbent assay) for the cytokines
Interleukin 10
measure IL-10 (Interleukin 10) via a bead-based, flow cytometric ELISA (enzyme-linked immunosorbent assay) for the cytokines
Albumin
measure concentration of albumin via BCG (bromocresol green) immunochemical analysis

Full Information

First Posted
June 26, 2023
Last Updated
July 10, 2023
Sponsor
Hope Biosciences
Collaborators
The University of Texas Health Science Center, Houston
search

1. Study Identification

Unique Protocol Identification Number
NCT05951777
Brief Title
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

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 2023 (Anticipated)
Primary Completion Date
December 2026 (Anticipated)
Study Completion Date
December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hope Biosciences
Collaborators
The University of Texas Health Science Center, Houston

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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 and/or hypoxic-ischemic encephalopathy in adults.
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 the first 4hr. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Traumatic Brain Injury
Keywords
severe, hypoxic-ischemic encephalopathy, intracranial hemorrhage, cerebral palsy, chronic, neurological injury

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
51 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment
Arm Type
Experimental
Arm Description
Autologous Adipose Derived Mesenchymal Stem Cells
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Normal Saline
Intervention Type
Biological
Intervention Name(s)
Autologous HB-adMSCs
Intervention Description
Hope Biosciences autologous adipose-derived mesenchymal stem cells
Intervention Type
Drug
Intervention Name(s)
Normal Saline
Intervention Description
Sterile Saline Solution 0.9%
Primary Outcome Measure Information:
Title
Glucose
Description
clinical lab evaluation of level of glucose in the blood (mg/dL)
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
Title
Calcium
Description
clinical lab evaluation of level of calcium in the blood (mg/dL) clinical lab evaluation of level of calcium in the blood (mg/dL) clinical lab evaluation of level of calcium in the blood (mg/dL)
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
Title
Albumin
Description
clinical lab evaluation of level of albumin in the blood (g/dL)
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
Title
Total Protein
Description
clinical lab evaluation of total protein in the blood (g/dL)
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
Title
Sodium
Description
clinical lab evaluation of total sodium in the blood (mmol/L)
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
Title
Total carbon dioxide
Description
clinical lab evaluation of total carbon dioxide in the blood (mmol/L)
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
Title
Potassium
Description
clinical lab evaluation of potassium in the blood (mmol/L)
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
Title
Chloride
Description
clinical lab evaluation of chloride in the blood (mmol/L)
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
Title
BUN (blood urea nitrogen)
Description
clinical evaluation of blood urea nitrogen (BUN) (mg/dL)
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
Title
Creatinine
Description
clinical evaluation of creatinine in blood (mg/dL
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
Title
Alkaline phosphatase
Description
clinical evaluation of alkaline phosphatase (ALP) in blood (IU/L)
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
Title
Alanine aminotransferase
Description
clinical evaluation of alanine aminotransferase (ALT) in blood (IU/L)
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
Title
Aspartate aminotransferase
Description
clinical evaluation of aspartate aminotransferase (AST) in blood (IU/L)
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
Title
Total Bilirubin
Description
clinical evaluation of total bilirubin in blood (mg/dL)
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
Title
White blood cell
Description
clinical evaluation of white blood cells (WBC) in blood (x 10^3/uL)
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
Title
Red blood cell
Description
clinical evaluation of red blood cells (RBC) in blood (x 10^6/uL)
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
Title
Hemoglobin
Description
clinical evaluation of hemoglobin in blood (g/dL)
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
Title
Hematocrit
Description
clinical evaluation of hematocrit in blood (%)
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
Title
Mean corpuscular volume
Description
clinical evaluation of mean corpuscular volume (MCV) in blood (fL)
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
Title
Mean corpuscular hemoglobin
Description
clinical evaluation of mean corpuscular hemoglobin (MCH) in blood (pg)
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
Title
Mean corpuscular hemoglobin concentration
Description
clinical evaluation of mean corpuscular hemoglobin concentration (MCHC) in blood (g/dL)
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
Title
Red cell distribution width
Description
clinical evaluation of red cell distribution width (RDW) in blood (%)
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
Title
Neutrophils
Description
clinical evaluation of neutrophils in blood (%)
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
Title
Lymphocytes
Description
clinical evaluation of lymphocytes in blood (%)
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
Title
Monocytes
Description
clinical evaluation of monocytes in blood (%)
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
Title
Eosinophils
Description
clinical evaluation of eosinophils in blood (%)
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
Title
Basophils
Description
clinical evaluation of basophils in blood (%)
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
Title
Absolute Neutrophils
Description
clinical evaluation of absolute neutrophils in blood (x 10^3/uL)
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
Title
Absolute lymphocytes
Description
clinical evaluation of absolute lymphocytes in blood (x 10^3/uL)
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
Title
Absolute monocytes
Description
clinical evaluation of absolute monocytes in blood (x 10^3/uL)
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
Title
Absolute eosinophils
Description
clinical evaluation of absolute eosinophils in blood (x 10^3/uL)
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
Title
Absolute basophils
Description
clinical evaluation of absolute basophils in blood (x 10^3/uL)
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
Title
Immature Granulocytes
Description
clinical evaluation of immature granulocytes in blood (%)
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
Title
Absolute Immature Granulocytes
Description
clinical evaluation of absolute immature granulocytes in blood (x 10^3/uL)
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
Title
Platelets
Description
clinical evaluation of platelets in blood (x 10^3/uL)
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
Title
Prothrombin Time
Description
clinical evaluation of time for blood to coagulate (seconds)
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
Title
INR (international normalized ratio)
Description
clinical evaluation of international normalized ratio of blood coagulation (no unit)
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
Title
Urine Pregnancy (if applicable)
Description
clinical evaluation of human chorionic gonadotropin (hCG) in urine (positive/negative)
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 Measure Information:
Title
Whole brain MRI (Magnetic resonance imaging)
Description
DTI (Diffusion tensor imaging) to assess macro- and micro-structural properties
Time Frame
Baseline, change from baseline at 6 months post-infusion
Title
PET/DT-MRI (positron emission tomography/Diffusion tensor-Magnetic resonance imaging)
Description
[11C]ER-176 (a Radioligand for 18-kDa (Translocator Protein)) tracer/label to identify brain proteins associated with neuroinflammatory response regulation
Time Frame
Baseline, change from baseline at 6 months post-infusion
Title
Glasgow Outcome Scale - Extended
Description
Dichotomized-Glasgow Outcomes Score (GOSE) to evaluate affect, functional outcome, and neuropsychological function. Minimum score = 1 = dead; 2 = vegetative state; 3 = lower severe disability; 4 = upper severe disability; 5 = lower moderate disability; 6 = upper moderate disability; 7 = lower good recovery; Maximum score = 8 = upper good recovery; Higher scores indicate better outcome.
Time Frame
Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
Title
Brain Injury Functional Outcome Measure
Description
High precision global functioning measure providing extended range and responsivity to change
Time Frame
Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
Title
Behavior Rating of Executive Functions-Adult
Description
Behavior Regulation and Metacognitive Indices assess everyday executive functions
Time Frame
Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
Title
TBI (Traumatic Brain Injury) Quality of Life Questionnaires
Description
TBI-QOL SF (Traumatic Brain Injury-Quality of Life Short-Form) measures physical, psychological health, cognitive, and participation outcomes: Cognition: minimum raw score = 10, maximum raw score = 50. A higher score represents better functioning. Communication/Comprehension: minimum raw score = 9, maximum raw score = 45. A higher score represents better functioning. Independence: minimum raw score = 8, maximum raw score = 40. A higher score represents better functioning. Mobility: minimum raw score = 9, maximum raw score = 45. A higher score represents better functioning. Satisfaction with Social Roles & Activities: minimum raw score = 10, maximum raw score = 50. A higher score represents better functioning. Upper Extremity Function: minimum raw score = 9, maximum raw score = 45. A higher score represents better functioning.
Time Frame
Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
Title
Brief Symptom Inventory 18
Description
Brief Symptom Inventory with 18 items contains three six-item scales for somatization, anxiety, depression, and the global Scale Global Severity Index (GSI). Each item is scored either 0 (Not at all), 1 (A little bit), 2 (Moderately), 3 (Quite a bit), 4 (Extremely), or R (Refused). The GSI therefore ranges between 0 (minimum) - 72 (maximum) and the three scales range between 0 (minimum) - 24 (maximum). Higher scores indicate worse outcome.
Time Frame
Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
Title
NIH Toolbox - Pattern Comparison Processing Speed Test
Description
An assessment of processing speed. Participants are asked to quickly determine whether two stimuli are the same or not the same. Participants are measured based on reaction time (seconds) and accuracy.
Time Frame
Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
Title
NIH Toolbox - Dimensional Change Card Sort Test
Description
An assessment of cognitive flexibility and attention. Participants are asked to match a series of bivalent test pictures (e.g., yellow balls and blue trucks) to the target pictures, first according to one dimension (e.g., color) and then, after a number of trials, according to the other dimension (e.g., shape). Participants are measured based on reaction time (seconds) and accuracy.
Time Frame
Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
Title
NIH Toolbox - Picture Vocabulary Test
Description
An assessment of receptive vocabulary administered in a computer-adaptive test (CAT) format. Participants must choose which of four pictures best represents a word presented via audio. Participants are measured based on reaction time (seconds) and accuracy.
Time Frame
Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
Title
NIH Toolbox - List Sorting Working Memory Test
Description
Designed to assess working memory (WM). List Sorting is a sequencing task requiring participants to sort and sequence stimuli that are presented visually and auditorily. Participants are measured based on accuracy.
Time Frame
Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
Title
NIH Toolbox - Flanker Inhibitory Control and Attention Test
Description
An assessment of inhibitory control and attention. The participant is asked to focus on a particular stimulus while inhibiting attention to the stimuli flanking it. Participants are measured based on reaction time (seconds) and accuracy.
Time Frame
Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
Title
NIH Toolbox - 9-hole Pegboard Dexterity Test
Description
The NIH Toolbox 9-Hole Pegboard Dexterity Test is a simple test of manual dexterity; it records the time required for the participant to accurately place and remove nine plastic pegs into a plastic pegboard. Raw scores are recorded as time in seconds that it takes the participant to complete the task with each hand (a separate score for each - Dominant vs. Non-Dominant Hand). Shorter time to complete the task indicates a better outcome. Longer time to complete the task indicates a worse outcome.
Time Frame
Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
Title
Rey Auditory Verbal Learning Test
Description
Immediate learning and delayed recall of a word list
Time Frame
Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
Title
Verbal Fluency
Description
Attentional control and verbal generativity
Time Frame
Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
Title
Wechsler Adult Intelligence Scale - IV: Processing Speed Index
Description
Information processing rate on paper-pencil tasks requiring visual attention. It is composed of 10 core subtests and five supplemental subtests, with the 10 core subtests comprising the Full Scale IQ. There are four index scores representing major components of intelligence: Verbal Comprehension Index (VCI); Perceptual Reasoning Index (PRI); Working Memory Index (WMI); Processing Speed Index (PSI) Two broad scores are also generated, which can be used to summarize general intellectual abilities: Full Scale IQ (FSIQ), based on the total combined performance of the VCI, PRI, WMI, and PSI; General Ability Index (GAI), based only on the six subtests that comprise the VCI and PRI The range of possible WAIS-IV (Wechsler Adult Intelligence Scale - IV) full scale IQs is 45-155. The WAIS-IV computes scaled scores for each individual based exclusively on chronological age. Higher score indicates better outcome.
Time Frame
Baseline, change from baseline at 6 months post-infusion, change from baseline at 1 year post-infusion
Title
Plasma cytokines
Description
measure plasma cytokines via a bead-based, flow cytometric ELISA (enzyme-linked immunosorbent assay) for the cytokines
Time Frame
Baseline imaging (visit #2), change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion
Title
Interleukin 1-alpha
Description
measure IL-1α (Interleukin 1-alpha) via a bead-based, flow cytometric ELISA (enzyme-linked immunosorbent assay) for the cytokines
Time Frame
Baseline imaging (visit #2), change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion
Title
Interleukin 4
Description
measure IL-4 (Interleukin 4) via a bead-based, flow cytometric ELISA (enzyme-linked immunosorbent assay) for the cytokines
Time Frame
Baseline imaging (visit #2), change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion
Title
Tumor necrosis factor alpha
Description
measure TNFα (Tumor necrosis factor alpha) via a bead-based, flow cytometric ELISA (enzyme-linked immunosorbent assay) for the cytokines
Time Frame
Baseline imaging (visit #2), change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion
Title
Interleukin 6
Description
measure IL-6 via a bead-based, flow cytometric ELISA (enzyme-linked immunosorbent assay) for the cytokines
Time Frame
Baseline imaging (visit #2), change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion
Title
Interleukin 10
Description
measure IL-10 (Interleukin 10) via a bead-based, flow cytometric ELISA (enzyme-linked immunosorbent assay) for the cytokines
Time Frame
Baseline imaging (visit #2), change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion
Title
Albumin
Description
measure concentration of albumin via BCG (bromocresol green) immunochemical analysis
Time Frame
Baseline imaging (visit #2), change from baseline at 6 months post-infusion, change from baseline 1 year post-infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adults between 18 and 55 years of age. Documented functional neurological damage to the central nervous system from closed head trauma that is 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. Ability to obtain consent from the subject or their legally authorized representative (LAR). Ability to communicate in English or Spanish (required for validated neurocognitive outcome testing). Exclusion Criteria: 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 eGFR (estimated glomerular filtration rate) > 60 mL/min/1.73m2); d) hepatic disease or altered liver function (screening SGPT (serum glutamate pyruvate transaminase) > 150 U/L or T. Bilirubin >1.3 mg/dL); e) cancer; f) immunosuppression (screening WBC (white blood cell) < 3, 000 cells/ml); g) HIV+ (human immunodeficiency virus positive); h) chemical or ETOH (Ethanol/Alcohol) 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; 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; m) individuals who have received a stem cell treatment. Normal brain CT/MRI (computed tomography/magnetic resonance imaging) exam. Spinal deformity, spinal surgery (including repeated epidural or spinal punctures), or complete spinal cord injury diagnosed by CT (computed tomography) or MR (magnetic resonance) imaging or by clinical findings. 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 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. Concurrent participation in interventional drug or device study. Inability to undergo the diagnostic tests (PET/DT-MRI (positron emission tomography/diffusion tensor-magnetic resonance imaging)) or unwilling/unable to cooperate with the diagnostic tests and outcome assessments. Metal implants including baclofen pumps that would preclude DT-MRI (Diffusion tensor-magnetic resonance imaging). Unwilling or unable to return for the follow-up study visits.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Steven Kosmach, MSN
Phone
713-500-7329
Email
steven.kosmach@uth.tmc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Charles S Cox, MD
Organizational Affiliation
The University of Texas Health Science Center, Houston
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Hermann Hospital / UTHealth McGovern Medical School at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Steven Kosmach, MSN
Phone
713-500-7329
Facility Name
Audie Murphy VA Hospital, Bartter Research Unit
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Steven Kosmach, MSN
Phone
713-500-7329

12. IPD Sharing Statement

Learn more about this trial

Autologous Adipose Derived Mesenchymal Stem Cells for Chronic Traumatic Brain Injury

We'll reach out to this number within 24 hrs