Clinical trial NCT05377281: Feasibility and Safety of AutoloGous UncondItioneD PEripheral Nerve Tissue Delivery to the Substantia Nigra (GUIDE)
Official title: Feasibility and Safety of AutoloGous UncondItioneD PEripheral Nerve Tissue Delivery to the Substantia Nigra
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Parkinson's Disease
Keywords: Peripheral nerve tissue
Lead sponsor: University of Kentucky
Sponsor class: OTHER
First posted: 2022-05-17
Enrollment: 10
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label, non-randomized, single-arm trial design to actively follow participants for 12 months. Ten participants will be enrolled to receive bilateral delivery of Peripheral Nerve Tissue (PNT) to the Substantia Nigra at the time of Deep Brain Stimulation (DBS) surgery. After 12 months, participants will be followed long term through annual visits for the rest of their lives. Participants will serve as their own donor for the tissue.

Detailed description: We recently designed open-label safety studies to investigate the use of an autologous source of cellular tissue from the peripheral nervous system (van Horne et al., 2017, 2018; Quintero et al. 2022), reparative peripheral (sural) nerve tissue containing a variety of cells and neuroprotective factors (Chau et al. 2022). While our previous studies have used injury-activated peripheral nerve tissue (PNT), where the sural nerve is transected and allowed to regenerate in situ for up to about 2 weeks before implantation, here we propose to use naïve, previously uninjured, nerve tissue delivered bilaterally to the substantia nigra at the time participants are undergoing deep brain stimulation (DBS) surgery. Participants will be assessed preoperatively, then undergo DBS surgery and delivery of autologous PNT, and then assessed postoperatively at two weeks after surgery, 6 months, 12 months and annually thereafter for adverse events and clinical outcomes.

Eligibility criteria: Inclusion Criteria:

* Undergoing DBS
* Diagnosis of clinically established or clinically probably PD (Parkinson's disease) as defined by MDS criteria
* Age 40-75, inclusive
* Able and willing to undergo ioflupane/SPECT
* Able to tolerate the surgical procedure
* Able to undergo all planned assessments
* Available access to the sural nerve

Exclusion Criteria:

* Any condition that would not make the subject a candidate for DBS
* Previous PD surgery or intracranial surgery
* Typical, nonparkinsonian syndrome ioflupane/SPECT signal
* Female who is pregnant, lactating, or of child-bearing potential unwilling to use an adequate birth control method during the period of the study
* Unable to undergo an MRI
* An obstructed trajectory path to the substantia nigra

Primary outcomes:
measure: Implantation of peripheral nerve tissue (PNT) into the substantia nigra
timeFrame: 12 months
Secondary outcomes:
measure: Adverse Events
timeFrame: 12 months
measure: Deployment
timeFrame: At the time of DBS surgery
measure: Procedure
timeFrame: At the time of DBS surgery
measure: Admission
timeFrame: Surgery
measure: Retention
timeFrame: 12 months
measure: Change in MDS-UPDRS scores
timeFrame: 12 months
measure: PDQ8 (Parkinson's Disease Questionnaire-8)
timeFrame: 12 months
measure: Schwab and England
timeFrame: 12 months
measure: Neurocognitive Testing
timeFrame: 12 months post-surgery
Other outcomes:
measure: Specific binding ratio
timeFrame: 12 months
Locations:
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
Study officials:
affiliation: University of Kentucky
name: Craig van Horne, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aparicio GI, Quintero JE, Plum L, Deng L, Wanczyk K, Henry M, Lynch E, Murphy M, Gerhardt GA, van Horne CG, Monje PV. Identification of cellular and noncellular components of mature intact human peripheral nerve. J Peripher Nerv Syst. 2024 Sep;29(3):294-314. doi: 10.1111/jns.12643. Epub 2024 Jul 7.
citation: van Horne CG, Quintero JE, Slevin JT, Anderson-Mooney A, Gurwell JA, Welleford AS, Lamm JR, Wagner RP, Gerhardt GA. Peripheral nerve grafts implanted into the substantia nigra in patients with Parkinson's disease during deep brain stimulation surgery: 1-year follow-up study of safety, feasibility, and clinical outcome. J Neurosurg. 2018 Dec 1;129(6):1550-1561. doi: 10.3171/2017.8.JNS163222. Epub 2018 Feb 18.
citation: Quintero JE, Slevin JT, Gurwell JA, McLouth CJ, El Khouli R, Chau MJ, Guduru Z, Gerhardt GA, van Horne CG. Direct delivery of an investigational cell therapy in patients with Parkinson's disease: an interim analysis of feasibility and safety of an open-label study using DBS-Plus clinical trial design. BMJ Neurol Open. 2022 Jul 14;4(2):e000301. doi: 10.1136/bmjno-2022-000301. eCollection 2022.
citation: Quintero JE, Chau MJ, Slevin JT, Koehl L, Gurwell JA, Wallace E, Kryscio RJ, El Khouli R, Anderson-Mooney AJ, Schmitt FA, Gerhardt GA, van Horne CG. Two-year feasibility and safety of open-label autologous peripheral nerve tissue implantation during deep brain stimulation in patients with Parkinson's disease. J Parkinsons Dis. 2025 Mar;15(2):397-408. doi: 10.1177/1877718X241312409. Epub 2025 Feb 25.