Adipose-derived Stromal Vascular Fraction Cells to Treat Parkinson

Study Overview
=================
Brief Summary
-----------------
This is an interventional study to treat 10 patients with a diagnosis of Parkinson's disease with neurological assessment from the Oxford Parkinson's Disease Quotient-39 (PDQ-39) and Movement Disorders Society Universal Parkinson's Disease Rating Scale (MDS-UPDRS), with autologous adipose tissue-derived stromal vascular fraction (SVF) cells by subdermal plane injection into the submuscular aponeurotic fascia of the face. This study assesses: 1) safety and 2) feasibility and 3) exploratory evidence of efficacy.

Detailed Description
-----------------
Pre-procedure/intervention evaluation Patients had a medical history, physical exam, and medication review. Neurological examination used two instruments: PDQ-39 and the MDS-UPDRS, the latter including videorecording of a standardized motor examination. Subjects also completed the general health questionnaire SF-36 and have blood drawn for subsequent biomarker analysis (immune markers L-1beta, IL-2, IL-6, IL-10, and TNF-alpha). Patients had pre-operative laboratory studies (hemogram, coagulation profile, electrolytes, BUN, creatinine, and urinalysis) and anesthesia evaluation carried out 48 hours prior to procedures. Surgical and biochemical technique The autologous fat tissue was harvested via liposuction by a plastic surgeon. The fat was washed and processed with collagenase for 60 minutes at a temperature of 39-41ºC, in an incubator and by constant shaking with a rotary shaker. The digested adipose tissue was then centrifuged for 14 minutes in 3 steps and the cell fraction (SVF) contained in the fat was removed with a syringe. The cell count was performed using a Luna Stem cell counter (Logos Bio). SVF was injected the same day as the liposuction and adipose processing. A standardized total dose of 30x10e6 SVF cells was administered [Carstens 2017]. Injections of SVF cells bilateral (into the subdermal plane along the submuscular aponeurotic fascia) 1 cc per site for a final dose of 0.3 million cells per site Post-surgical and management of complications Patients were observed for potentially adverse effects for 24 hours after the procedure. There were follow-up visits at seven days, 1-, 3-, 6- and 12 months postoperative and treatment period.

Official Title
-----------------
Treatment of Parkinson Disease With Transplantation of SVF Cells of Adipose Origin: Safety and Exploratory Efficacy Study

Conditions
-----------------
Idiopathic Parkinson Disease, Parkinson's Disease and Parkinsonism

Intervention / Treatment
-----------------
* Genetic: Adipose-derived stromal vascular fraction cells


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects with UK brain bank criteria for idiopathic Parkinson's disease for a period of not less than one year Age 18 - 80; male or female Stable PD medication for at least 30 days prior to study enrollment A MDS-UPDRS total score > 20 and < 50 Ability to understand the study and sign consent forms Intent to comply with all postoperative appointments Social support to be able to comply with all follow-up visits Exclusion Criteria: Previous neurological disease or previous brain trauma as a confounding factor Cardiovascular disease or any condition that prohibits general anesthesia Inability to understand and / or cooperate with investigators Subjects that have a history of injury, infection, or deformity of at or near the anatomical site for planned product injection which may increase their risk for infection, injury, or complication related to the product (e.g., prior injury to blood vessels, lymphatics, history of orbital injury/fracture). Rash or possible skin infection over surgical sites or face. Subjects that use any form of tobacco, including e-cigarettes, more than once a week over the past year. Current substance abuse (drugs or alcohol) within the 6 months prior to study enrollment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

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

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

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

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single group assignment.<br>Bilateral treatment. Subdermal plane injection of SVF cells into the submuscular aponeurotic fascia of the face. | Genetic: Adipose-derived stromal vascular fraction cells<br>* Published minimal clinically important differences (MCID) for PDQ-39; MDS-UPDRS; and levo-dopa equivalent dose and changes in the levels of blood proteins (L-1beta, IL-2, IL-6, IL-10, and TNF-alpha) in 10 patients after 12 months of treatment with SVF cells.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment related adverse events | Documentation of adverse events | 12-months follow-up post intervention. | 
| L-dopa medication | Changes in L-dopa medication measured as levodopa-equivalent dose. | Up to month 12 post intervention. | 
| Minimal clinically important differences (MCIDs)-1 | Estimation of MCIDs scores (0-199) based on the UPDRS scale: : MCID 4.3 points low, MCID 8.1 points medium, and MCID 17.1 points high. | Up to 12-months post SVF treatment | 
| Minimal clinically important differences (MCIDs)-2 | Estimation of MCIDs scores (0-100) based on the PDQ-39 scale: : MCID 4.7 minimal, MCID 7.7 moderate, and MCID 10.1 significant. | Up to 12-months post SVF treatment |