Use of Cellular Stromal Vascular Fraction in Multiple Sclerosis,Autoimmune, Inflammatory, Neurologic Conditions

Study Overview
=================
Brief Summary
-----------------
Purpose of study is to determine safety and efficacy of use of autologous Adipose-Derived cellular Stromal Vascular Fraction (AD-cSVF) suspended in Normal Saline and delivered via intravascular system of quality of life and alteration of documented Muscular Sclerosis (MS) and related neurodegenerative patients. It is believed that the heterogeneous cell population which includes multipotent stem/stromal cells are capable of immune modulation/inflammatory modulation properties. Exam of disease progression and quality of life changes will be evaluated.

Detailed Description
-----------------
Multiple Sclerosis (MS) is a demyelination disease which features damage to insulating covers of nerve cells in the brain and spinal cord. This damage or degenerative changes disrupts the ability of parts of the nervous system to communicate, resulting in range of signs and symptoms which include physical and mental changes. Symptoms are variable and often include visual changes, sensory irregularities, and motor coordination. MS has several forms which result in new symptoms in either isolated attacks (relapsing forms) or gradual increasing symptoms (progressive forms). While cause is not clear, mechanisms have been suggested association with loss of the immune system or failure to produce myelin-producing cells. Some suggest a genetic predisposition or environmental factor, but the exact causation in all cases have not been elucidated. Medications have been developed, but remain modestly effective and possessing major side effects and poorly tolerated. Alternative treatments, including physical therapy and some stem/stromal therapies have become more common. Three main characteristics of MS are: 1). Lesion formations in the central nervous system (called Plaques); 2). Inflammation; 3). Destruction of myelin sheaths of neurons. This demyelination is thought to stimulate the inflammatory processes due to action of a lymphocyte group known at T-cell which seems to recognize patient's own myelin as foreign and proceeds to attack it (known as autoreactive lymphocytes). Traditionally, exacerbation's are often treated with high dose intravenous steroids which may be of short term reduction of symptoms, not addressing the underlying causation. Current medications available for treatment are expensive and fraught with major side effects, making their use very difficult and producing limited measured value. With the advent of convenient adipose harvesting and processing in closed systems, the ability to easily and safely acquire significant of stem/stromal cells, studies are underway to utilize autologous stem/stromal cells. This study is aimed at evaluation of the safety profile (adverse reactions & severe adverse reaction) of the closed syringe, microcannula harvesting of subdermal fat deposits. This autologous cell group obtained with isolation and concentration of cells within the stromal vascular fraction (SVF) via enzymatic digestion, and deployed via intravascular routes. As these cells are very small, there is belief that they are able to pass into the cerebral fluids in defects of the blood brain barrier (BBB) or are small enough to pass into the fluids of the CNS (central nervous system).

Official Title
-----------------
Use of Cellular Stromal Vascular Fraction (cSVF) for Select Multiple Sclerosis, Autoimmune, Inflammatory, and Neurologic Conditions: Clinical Interventional Study of Adverse Events and Clinical Outcomes Using Autologous Stem-Stromal Cells.

Conditions
-----------------
Multiple Sclerosis, Autoimmune

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Documented functional damage to central or peripheral nervous system unlikely to improve with present standard of care At least 6 months after onset of disease process If under current medical therapy (drug or surgical) for the condition, patient considered stable on that treatment and unlikely to have significant reversal of associated neurological functions damage as a result of ongoing treatments In estimation of providers and neurologists have the potential for improvement with AD-cSVF treatment, and be at minimal risk of potential harm from the procedure Over 18 year old, and capable of providing informed consent Medically stable and cleared by primary care physician, neurologist, or licensed practitioner that patient is felt to be reasonably expected to be expected to undergo procedures without known significant risk to health Exclusion Criteria: Patient must be capable of an adequate neurologic examination and evaluation to document the pathology and ability to cooperate with examination Patient much be capable and willing to undergo follow up neurologic exams with investigators or their own neurologists Patient must be capable and competent to provide informed consent to participation In estimation of investigators, the patient may be at increased or significant risk of harm to the patient's general health or neurologic functions for collection of AD-cSVF collection Patients not medically stable, or who may be at significant risk to their health undergoing any and all procedures will not be eligible Women of childbearing age must not be pregnant at the time of treatment, and should refrain from becoming pregnant for 3 months post-treatment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Microcannula Harvest Adipose<br>Acquisition AD-tSVF via closed syringe microcannula | Procedure: Microcannula Harvest Adipose<br>* Use of Closed Syringe Microcannula Harvest Autologous Adipose-Derived Stem/Stromal Cells<br>|
| Experimental: Centricyte 1000<br>Autologous Adipose-Derived Tissue Stromal Vascular Fraction (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 adipose tissue stromal vascular fraction to create a AD-cSVF<br>|
| Experimental: Sterile Normal Saline<br>Re-suspension of Autologous 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 [Time Frame: Outcome measures evaluated at baseline and reviewed at 6 month intervals for average time frame of 5 years] | Activities of Daily Living (ADL) | 6 month intervals for up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurologic Functioning | Deficits of neurologic function identified by patient as impaired prior to treatment assessed. Examples: neurologic function may include speech, balance, motor/sensory actions, hearing, gait, strength, pain, paresthesias | 6 month intervals for up to 5 years | 
| Quality of Life Questionnairre | Change from baseline in overall General Quality of Life (GQL) Health status questionnaire (SF-36) | 1 year | 
| Fatigue | Change from baseline measured by modified fatigue impact scale (MFIS) | 6 month intervals for up to 5 years | 
| Cognitive Problems | Cognitive Problems measured by Perceived Deficits Questionnaire (PDQ) | 1 year intervals for up to 5 years | 
| Brain Lesions | PIXYL Software Analysis from Baseline and at 6 month MRI with/without contrast Brain | 6 month intervals for up to 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Multiple Sclerosis, Demyelinating Diseases, Nervous System Diseases, Autoimmune Disorders