Feasibility and Safety of autoloGous UncondItioneD pEripheral Nerve Tissue Delivery to the Substantia Nigra (GUIDE) (GUIDE)

Feasibility and Safety of autoloGous UncondItioneD pEripheral Nerve Tissue Delivery to the Substantia Nigra

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Parkinson's Disease
• Intervention / Treatment: Procedure: Peripheral Nerve Tissue Implantation

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.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University Of Kentucky

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Implantation of peripheral nerve tissue; Bilateral deployment of peripheral nerve tissue to the substantia nigra.

Procedure: Peripheral Nerve Tissue Implantation; 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 substantia nigra.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Implantation of peripheral nerve tissue (PNT) into the substantia nigra	Successful bilateral graft delivery to the substantia nigra at a proportion = 70%.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Number of adverse events and serious adverse events associated with bilateral PNT deployment to the substantia nigra.	12 months
Deployment	Number of deployment attempts required to deliver bilateral PNT	At the time of DBS surgery
Procedure	Duration of procedure.	At the time of DBS surgery
Admission	Length of hospital stay (days).	Surgery
Retention	Percent of study visits completed.	12 months
Change in MDS-UPDRS scores	Mean change in MDS-UPDRS (Movement Disorder Society-Unified Parkinson's Disease Rating Scale) Part III scores for participants at 12, and 6 months compared to baseline. Mean change of the MDS-UPDRS Part I scores for participants at 6,12 months compared to baseline. Mean change of the MDS-UPDRS Part II scores for participants at 6,12 months compared to baseline. (95% confidence interval) Scale runs from 0-132 with smaller scores indicating fewer symptoms.	12 months
PDQ8 (Parkinson's Disease Questionnaire-8)	Mean change of the PDQ-8, Modified scores for participants at 6, 12 months compared to baseline. (95% confidence interval). Scale runs from 0-32 with lower scores indicating fewer symptoms.	12 months
Schwab and England	Mean change of the Modified Schwab and England Scale scores for participants at 6, 12 months compared to baseline. (95% confidence interval). Scale runs from 0%-100% with a higher score indicating the participant has more independence in their daily activities.	12 months
Neurocognitive Testing	Mean change for neuropsychological assessment scores at 12 months compared to baseline. (95% confidence interval)	12 months post-surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Specific binding ratio	Mean change in specific binding ratio in the posterior putamen for participants at 12 months compared to baseline (95% confidence interval).	12 months

Collaborators and Investigators

• Sponsor: Craig van Horne, MD, PhD
• Investigators: Principal Investigator: Craig 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.
• 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.
• 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 7, 2022
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: May 4, 2022
• First Submitted That Met QC Criteria: May 11, 2022
• First Posted (Actual): May 17, 2022

Study Record Updates

• Last Update Posted (Estimated): October 28, 2025
• Last Update Submitted That Met QC Criteria: October 24, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Peripheral nerve tissue
• 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: 76436

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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