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 (STAR)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Parkinson's Disease
• Intervention / Treatment: Procedure: Reparative Autologous peripheral nerve tissue

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jaimie Hixson; Phone Number: 8593231908; Email: jaimie.henderson@uky.edu
• Study Contact Backup: Name: Group Monitored Email; Email: nervegraft@uky.edu

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Recruiting
      • University Of Kentucky
      • Contact: Jaimie Hixson; Phone Number: 859-323-1908; Email: jaimie.henderson@uky.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Peripheral nerve tissue (PNT) deployment to the Substantia Nigra	Procedure: Reparative Autologous peripheral nerve tissue; At the time participants are receiving the standard of care deep brain stimulation (DBS) surgery, a standard incision on the lateral aspect near the ankle is made, the sural nerve is identified, an about 3 cm biopsy of the sural nerve is obtained and the incision is closed. From the biopsied section, the epineurium is removed, fascicles are cut, and (~5 pieces per side; ~ 5mm length x 1.5 mm diameter: approximately 10 cubic millimeters) implanted bilaterally into the nucleus basalis of Meynert (NBM) or substantia nigra (SN).
Active Comparator: Peripheral nerve tissue (PNT) deployment to the nucleus basalis of Meynert	Procedure: Reparative Autologous peripheral nerve tissue; At the time participants are receiving the standard of care deep brain stimulation (DBS) surgery, a standard incision on the lateral aspect near the ankle is made, the sural nerve is identified, an about 3 cm biopsy of the sural nerve is obtained and the incision is closed. From the biopsied section, the epineurium is removed, fascicles are cut, and (~5 pieces per side; ~ 5mm length x 1.5 mm diameter: approximately 10 cubic millimeters) implanted bilaterally into the nucleus basalis of Meynert (NBM) or substantia nigra (SN).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Successful deployment of bilateral peripheral nerve tissue (PNT) into the brain	Number of participants in each study arm who successfully receive bilateral PNT delivery.	Intraoperative
Number of participants completing 12 month study visit	Total number of participants to complete study visit by arm assignment	12-month study visit
Study-related adverse events as assessed by MedDRA v27	Total number of study-related adverse events experienced by participants.	Enrollment to 24-month study visit
Study-related serious adverse events as assessed by MedDRA v.27	Total number of serious adverse events experienced by participants	Enrollment to 24-month study visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PNT deployment attempts	Number of deployment attempts required, per participant, to deliver bilateral PNT by group allocation	During surgery
Mean change in Montreal Cognitive Assessment (MoCA) scores	Mean change in MoCA scores for participants at study visits compared to baseline by group allocation. Assessment is scored from 0-30 with a score of 26 or better indicating normal cognition. A score less than 26 indicates a cognitive deficit.	Baseline 6, 12 and 24 months after surgery
Mean change in Neuropsychological assessment scores	Participants complete a neuropsychological assessment battery that meets the Movement Disorder Society (MDS) guidelines for determining mild cognitive impairment/mild neurocognitive disorder. Domains include attention and working memory, executive functioning, memory (verbal and visual), language, and visuospatial skills. Participants' raw scores will be converted to standardized scores based on appropriate norms (e.g., age-based norms). Participants' 12 and 24-month re-evaluation will be compared to their baseline pre-surgical assessment to determine change from baseline on each measure. A change that exceeds 1.5 standard deviation from their baseline performance will be considered notable.	Baseline, 12 and 24 months
Change in Neuropsychological diagnosis	Changes in participant neuropsychological diagnoses during scheduled evaluations will be reported. e.g. No cognitive diagnosis progressing to mild neurocognitive disorder.	Baseline, 12 and 24 months
Change in Neuropsychological domains with impairment	A count of the number of domains with impairment at each study visit to compare with previous study visits.	At 12, 24 months compared to baseline
Mean change in Modified Schwab and England Scale of Activities of Daily Living scores	Mean change participant independence levels as measured in Schwab and England Scale of Activities of Daily Living scores. 100% = completed independent and 0% being completely dependent.	At 6, 12, 24 months compared to baseline
Mean change in Parkinson's Disease Questionnaire-8 (PDQ-8) quality of life scores	Assess changes in participant's quality of life. Questionnaire is scored from 0-32 with higher scores indicating poorer quality of life.	At 12 and 24 months compared to baseline
Mean change in Non-motor symptom scale scores	Assessment used to identify Parkinson's disease related non-motor symptoms experienced by participants. The scale measures the frequency and severity of symptoms and is scored from 0-360 with higher scores indicating more frequent and severe symptoms.	At 12 and 24 months compared to baseline
Mean change of the Movement Disorder Society - Unified Parkinsons Disease Rating Scale (MDS-UPDRS) Part I scores	MDS-UPDRS Part I scores non-motor symptoms effecting activities of daily living in those with Parkinson's Disease. Scores range from 0-52 with higher scores indicating greater symptom severity.	6, 12, and 24 months as compared to baseline
Mean change of the MDS-UPDRS Part II scores	MDS-UPDRS Part II scores motor symptoms effecting activities of daily living in those with Parkinson's Disease. Scores range from 0-52 with higher scores indicating greater symptom severity.	At 6, 12, 24 months compared to baseline
Mean change in MDS-UPDRS Part III scores	MDS-UPDRS Part III scores motor symptoms associated with Parkinson's Disease. Part III scores range from 0-132 with higher scores indicating higher symptom severity.	At 6, 12, 24 months compared to baseline
Mean change in MDS-UPDRS Part IV scores	MDS-UPDRS Part IV scores motor complications such as fluctuations and dyskinesia's associated with anti-Parkinson's medications. Scores range from 0-24 with higher scores indicating greater severity in motor complications.	At 6, 12, and 24 months compared to baseline
Number of participants completing 24-month study visit	Total number of participants completing 24 month study visit by group allocation	24-month study visit
Mean change in Dementia Rating Scale (DSRS)	A survey to assess and rate changes the cognitive and behavioral functioning of participants. Scale is scored from 0-54 with being higher numbers indicating greater dementia severity.	Baseline 6, 12 and 24 months after surgery

Collaborators and Investigators

• Sponsor: Craig van Horne, MD, PhD
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Craig G van Horne, MD, PhD, University Of Kentucky

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): February 28, 2028

Study Registration Dates

• First Submitted: November 7, 2024
• First Submitted That Met QC Criteria: November 8, 2024
• First Posted (Actual): November 12, 2024

Study Record Updates

• Last Update Posted (Actual): August 14, 2025
• Last Update Submitted That Met QC Criteria: August 11, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Parkinson's Disease; Deep Brain Stimulation; DBS; Cell and Tissue Based Therapy
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease
• Other Study ID Numbers: 90066; 1R01AG081356-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The focus of this study is PD, but images and results will be made available to other researchers by asking participants, at the time of consent, their willingness to permit sharing of data and bio-specimens.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No