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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Procedure: Peripheral Nerve Tissue Implantation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Implantation of peripheral nerve tissue<br>Bilateral deployment of peripheral nerve tissue to the substantia nigra. | Procedure: Peripheral Nerve Tissue Implantation<br>* 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 epinerium 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peripheral nerve tissue