Feasibility and Safety of AutoloGous UncondItioneD PEripheral Nerve Tissue Delivery to the Substantia Nigra (GUIDE)

Phase 1

Active, not recruiting

• Conditions: Parkinson's Disease
• Interventions: Procedure: Peripheral Nerve Tissue Implantation

• Registration Number: NCT05377281
• Lead Sponsor: Craig van Horne, MD, PhD

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.

Study Timeline

• Study First Submitted: 2022-05-04
• Study First Submitted QC: 2022-05-11
• Study First Posted: 2022-05-17
• Study Start: 2022-07-07
• Status Verified: 2024-10
• Last Update Submitted: 2025-03-20
• Last Update Posted: 2025-03-25
• Primary Completion: 2027-06-30
• Study Completion: 2027-06-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 10

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Implantation of peripheral nerve tissue	Peripheral Nerve Tissue Implantation	Bilateral deployment of peripheral nerve tissue to the substantia nigra.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Deployment	At the time of DBS surgery	Number of deployment attempts required to deliver bilateral PNT
Procedure	At the time of DBS surgery	Duration of procedure.
PDQ8 (Parkinson's Disease Questionnaire-8)	12 months	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.
Change in MDS-UPDRS scores	12 months	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.
Neurocognitive Testing	12 months post-surgery	Mean change for neuropsychological assessment scores at 12 months compared to baseline. (95% confidence interval)
Adverse Events	12 months	Number of adverse events and serious adverse events associated with bilateral PNT deployment to the substantia nigra.
Schwab and England	12 months	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.
Admission	Surgery	Length of hospital stay (days).
Retention	12 months	Percent of study visits completed.

Trial Locations

Locations (1)

University of Kentucky; 🇺🇸 Lexington, Kentucky, United States