Use of Adipose-Derived Stem/Stromal Cells in Concussion and Traumatic Brain Injuries

Study Overview
=================
Brief Summary
-----------------
Concussion is the most common type of brain injury throughout life. Study is seeking improvement of long-term residua following adolescent and adult post-traumatic injuries often associated with contact sports and accidental causes. Typically defined as reversible head injury with temporary loss of brain function. Symptoms range from physical, cognitive, pain (headache) and emotional signs consistent with TBI and Post-Traumatic Stress Syndrome. Use of AD-cSVF parenteral delivery to encourage repair of damage and decreased function following concussion, particularly in contact, repetitive sports injuries. Range of damage is measured in Grade I-III according to graduated severity. Unfortunately, less information is available about repetitive concussions and the long-term health issues.

Detailed Description
-----------------
Concussion Syndrome (CS) and TBI are common injuries producing temporary and long-term damage to impact brain function. Symptoms are sometimes transient, sometimes long-term depending on severity and/or repetitive damage. Signs varying from recurrent headaches, mental fog, emotional changes to physical signs of loss of consciousness, amnesia to behavioral change (irritability, loss of concentration ability, etc.), cognitive impairment (slow reaction times, memory loss), and recurring sleep disturbances. Common causes include sports injuries, automobile accidents, falls, blunt trauma to head, and explosive/blast injuries from production of acceleration injuries Treatment often involves monitoring, physical rest, limiting cognitive activities (such as computing, video games, texting, and studying). Most often a single episode usually resolve or improve (particularly in recurring headaches) within 3-4 weeks. It is estimated that >6/1000 occurrence rate apply. Repetitive injuries seem to make the person more susceptible to additional damage, particularly with injury precedes resolution of an earlier damage. There appears also to make persons to require a lesser impact to produce the same degree of severity. It is becoming more recognized that repeated concussions increase the risks in later life for dementia, Parkinson's and severe depressions. Most serious signs to evaluate are loss of consciousness, seizures, worsening headache, diplopia/pupil changes, loss of recognition, vomiting, focal neurological problems, and change of personality. There is no consensus definition of concussion or TBI. Most concussions are considered in the mild TBI (mTBI) group, and are rarely demonstrate structural brain damage when in the acute to subacute state. Late brain MRI changes are difficult to clearly point to or identify the specific areas of presumed damage. This study is intended to examine safety and efficacy of parenteral introduction of AD-cSVF in cases of CS and TBI, and categorically examine the outcomes according to the elapsed time from original concussive event. No delineation of those having recurrent damage and injuries are made within this study.

Official Title
-----------------
Use of Adipose-Derived Cellular Stromal Vascular Fraction (AD-cSVF) Parenterally in Post-Concussion Injuries and Traumatic Brain Injuries (TBI)

Conditions
-----------------
Traumatic Encephalopathies, Chronic, Concussion, Mild, Concussion, Intermediate, Concussion, Severe, Concussion, Brain

Intervention / Treatment
-----------------
* Procedure: Microcannula Harvest Adipose
* Device: Centricyte 1000
* Procedure: Sterile Normal Saline IV deployment AD-cSVF


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Documented history of mTBI or TBI with Correlated MRI or CT At least 1 month post mTBI and TBI Able and Willing to participate in CT or MRI pre-study and at 3 year, 5 year interval Able to provide informed consent to undergo the study Depression, Cognitive Disability, Attention Disorders, Headaches or other persistent changes which followed a traumatic brain event (TBI) Impaired social or occupational functioning following mTBI or TBI History of repetitive events for mTBI and TBI Exclusion Criteria: Documented history of neuro-degenerative illness, seizures, mental illness, or severe medical conditions preceding mTBI or TBI Malignances, Bleeding Disorders, Pregnancy or Lactation Tumors of Central Nervous System (CNS) Lack of adequate donor tissue volume as determined by the primary investigator at their discretion Any pre-existing medical condition which, in view of the primary investigator and patient's primary care physician, would prevent participation in study

Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Microcannula Harvest Adipose<br>Acquisition Adipose-Derived Tissue Stromal Vascular Fraction (AD-tSVF) via close syringe microcannula harvest from subdermal fat deposits | Procedure: Microcannula Harvest Adipose<br>* Use of Closed Syringe Microcannula Harvest Autologous Adipose-Derived Stem/Stromal Cells<br>|
| Experimental: Centricyte 1000<br>Autologous AD-tSVF via enzymatic isolation/concentration via Centricyte 1000 Closed System to create AD-cSVF | Device: Centricyte 1000<br>* Use of Centricyte 1000 Closed System Digestion Autologous AD-tSVF to create AD-cSVF<br>|
| Experimental: Sterile Normal Saline<br>Re-suspension of AD-cSVF pellet in Normal Saline deployment via IV | Procedure: Sterile Normal Saline IV deployment AD-cSVF<br>* Sterile Normal Saline Suspension AD-cSVF in 500 cc IV use<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events | Activities of Daily Living (ADL) | Outcome measures at baseline at 6 month | 
| Cognitive Change in clinical symptoms associated with concussion-TBI | Montreal Cognitive Assessment Scale (MCAS) | Outcome measures at baseline and reviewed 1 year interval for average time 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Beck's Depression Inventory (BDI) | Multiple choice self reporting measure of depression | Annual for 5 years | 
| Adult Attention Deficit Assessment | Conner's Adult Attention Deficit Disorder Rate Scale (CAADDR) | Annual for 5 years | 
| MRI Brain With & MRI Brain With & Without Contrast | MRI Brain to evaluate progressive changes comparing pre-treatment (0), 3 year and 5 year status | 0, 3 years, 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
TBI, mTBI, Concussion, Brain, Loss Consciousness, Traumatic, Headaches