Parkinson's Disease
Conditions
Keywords
Peripheral nerve tissue
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.
Interventions
PROCEDUREPeripheral 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.
Sponsors
Craig van Horne, MD, PhD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | 12 months | Number of adverse events and serious adverse events associated with bilateral PNT deployment to the substantia nigra. |
| 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. |
| Admission | Surgery | Length of hospital stay (days). |
| Retention | 12 months | Percent of study visits completed. |
| 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. |
| 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. |
| 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. |
| Neurocognitive Testing | 12 months post-surgery | Mean change for neuropsychological assessment scores at 12 months compared to baseline. (95% confidence interval) |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORCraig van Horne, MD, PhD
University of Kentucky
Outcome results
None listed