Clinical trial NCT06683378: A Study to Evaluate Feasibility, Safety, and Clinical Responses of Implanting Autologous Peripheral Nerve Tissue Into the Brain for Non-motor or Motor Symptoms in Patients With Parkinson's Disease Undergoing DBS Surgery
Official title: Phase I Randomized, Double-blind Study to Evaluate Feasibility, Safety, and Clinical Responses of Implanting Autologous Peripheral Nerve Tissue Into the Nucleus Basalis of Meynert or Substantia Nigra for Non-motor or Motor Symptoms in Patients With Parkinson's Disease Undergoing DBS Surgery
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Parkinson's Disease
Keywords: Parkinson's Disease
Deep Brain Stimulation
DBS
Cell and Tissue Based Therapy
Lead sponsor: University of Kentucky
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2024-11-12
Enrollment: 24
Sex: ALL
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators propose a Phase I single surgical-center, double-blinded randomized parallel clinical trial involving bilateral autologous peripheral nerve tissue (PNT) delivery into the NBM or the alternate target also affecting cognition in this population, the substantia nigra (SN), to address "repair cell" support of these areas. Twenty-four participants with idiopathic Parkinson's Disease (PD) who have selected, qualified and agreed to receive as standard of care deep brain stimulation (DBS) will be enrolled and randomly allocated to receive bilateral PNT deployment to either the NBM or SN at the time of DBS surgery. Participants will be allocated equally among both assignments over the course of three years (8 Year 1, 10 Year 2, 6 Year 3). Participants will be evaluated for neurocognitive, motoric function, activities of daily living, and quality of life at enrollment before surgery, two-weeks after surgery, and 6, 12, and 24 months after surgery.


Eligibility criteria: Inclusion Criteria:

* Undergoing DBS
* Diagnosis of clinically established or clinically probably PD as defined by MDS criteria
* Age 45-75, inclusive
* 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
* Dementia diagnosis
* Previous PD surgery or intracranial surgery
* Unable to undergo an MRI
* An obstructed trajectory path to the substantia nigra and nucleus basalis of Meynert

Primary outcomes:
measure: Successful deployment of bilateral peripheral nerve tissue (PNT) into the brain
timeFrame: Intraoperative
measure: Number of participants completing 12 month study visit
timeFrame: 12-month study visit
measure: Study-related adverse events as assessed by MedDRA v27
timeFrame: Enrollment to 24-month study visit
measure: Study-related serious adverse events as assessed by MedDRA v.27
timeFrame: Enrollment to 24-month study visit
Secondary outcomes:
measure: PNT deployment attempts
timeFrame: During surgery
measure: Mean change in Montreal Cognitive Assessment (MoCA) scores
timeFrame: Baseline 6, 12 and 24 months after surgery
measure: Mean change in Neuropsychological assessment scores
timeFrame: Baseline, 12 and 24 months
measure: Change in Neuropsychological diagnosis
timeFrame: Baseline, 12 and 24 months
measure: Change in Neuropsychological domains with impairment
timeFrame: At 12, 24 months compared to baseline
measure: Mean change in Modified Schwab and England Scale of Activities of Daily Living scores
timeFrame: At 6, 12, 24 months compared to baseline
measure: Mean change in Parkinson's Disease Questionnaire-8 (PDQ-8) quality of life scores
timeFrame: At 12 and 24 months compared to baseline
measure: Mean change in Non-motor symptom scale scores
timeFrame: At 12 and 24 months compared to baseline
measure: Mean change of the Movement Disorder Society - Unified Parkinsons Disease Rating Scale (MDS-UPDRS) Part I scores
timeFrame: 6, 12, and 24 months as compared to baseline
measure: Mean change of the MDS-UPDRS Part II scores
timeFrame: At 6, 12, 24 months compared to baseline
measure: Mean change in MDS-UPDRS Part III scores
timeFrame: At 6, 12, 24 months compared to baseline
measure: Mean change in MDS-UPDRS Part IV scores
timeFrame: At 6, 12, and 24 months compared to baseline
measure: Number of participants completing 24-month study visit
timeFrame: 24-month study visit
measure: Mean change in Dementia Rating Scale (DSRS)
timeFrame: Baseline 6, 12 and 24 months after surgery
Other outcomes:
Locations:
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
Study officials:
affiliation: University of Kentucky
name: Craig G van Horne, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.