Clinical trial NCT05699161: Adipose-derived Stromal Vascular Fraction Cells to Treat Parkinson
Official title: Treatment of Parkinson Disease With Transplantation of SVF Cells of Adipose Origin: Safety and Exploratory Efficacy Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Idiopathic Parkinson Disease
Parkinson's Disease and Parkinsonism
Lead sponsor: National Autonomous University of Nicaragua
Sponsor class: OTHER
Collaborators: name: Wake Forest University
name: Ministerio de Salud, Nicaragua
name: GID BIO, Inc.
name: National Autonomous University of Nicaragua
First posted: 2023-01-26
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence of treatment related adverse events
timeFrame: 12-months follow-up post intervention.
measure: L-dopa medication
timeFrame: Up to month 12 post intervention.
measure: Minimal clinically important differences (MCIDs)-1
timeFrame: Up to 12-months post SVF treatment
measure: Minimal clinically important differences (MCIDs)-2
timeFrame: Up to 12-months post SVF treatment
Secondary outcomes:
Other outcomes:
Locations:
city: León
country: Nicaragua
facility: Hospital Escuela Oscar Danilo Rosales Arguello
state: Leon
Study officials:
References:
citation: Carstens M, Haq I, Martinez-Cerrato J, Dos-Anjos S, Bertram K, Correa D. Sustained clinical improvement of Parkinson's disease in two patients with facially-transplanted adipose-derived stromal vascular fraction cells. J Clin Neurosci. 2020 Nov;81:47-51. doi: 10.1016/j.jocn.2020.09.001. Epub 2020 Sep 25.
citation: Brown JC, Shang H, Li Y, Yang N, Patel N, Katz AJ. Isolation of Adipose-Derived Stromal Vascular Fraction Cells Using a Novel Point-of-Care Device: Cell Characterization and Review of the Literature. Tissue Eng Part C Methods. 2017 Mar;23(3):125-135. doi: 10.1089/ten.TEC.2016.0377.
citation: Nguyen A, Guo J, Banyard DA, Fadavi D, Toranto JD, Wirth GA, Paydar KZ, Evans GR, Widgerow AD. Stromal vascular fraction: A regenerative reality? Part 1: Current concepts and review of the literature. J Plast Reconstr Aesthet Surg. 2016 Feb;69(2):170-9. doi: 10.1016/j.bjps.2015.10.015. Epub 2015 Oct 31.
citation: Guo J, Nguyen A, Banyard DA, Fadavi D, Toranto JD, Wirth GA, Paydar KZ, Evans GR, Widgerow AD. Stromal vascular fraction: A regenerative reality? Part 2: Mechanisms of regenerative action. J Plast Reconstr Aesthet Surg. 2016 Feb;69(2):180-8. doi: 10.1016/j.bjps.2015.10.014. Epub 2015 Oct 24.
citation: Lindvall O. Treatment of Parkinson's disease using cell transplantation. Philos Trans R Soc Lond B Biol Sci. 2015 Oct 19;370(1680):20140370. doi: 10.1098/rstb.2014.0370.
citation: Shulman LM, Gruber-Baldini AL, Anderson KE, Fishman PS, Reich SG, Weiner WJ. The clinically important difference on the unified Parkinson's disease rating scale. Arch Neurol. 2010 Jan;67(1):64-70. doi: 10.1001/archneurol.2009.295.
citation: Horvath K, Aschermann Z, Kovacs M, Makkos A, Harmat M, Janszky J, Komoly S, Karadi K, Kovacs N. Changes in Quality of Life in Parkinson's Disease: How Large Must They Be to Be Relevant? Neuroepidemiology. 2017;48(1-2):1-8. doi: 10.1159/000455863. Epub 2017 Feb 4.