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.
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
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
Parallel
Reparative Autologous peripheral nerve tissue
Procedure/SurgeryAt 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).
Successful deployment of bilateral peripheral nerve tissue (PNT) into the brain
Number of participants in each study arm who successfully receive bilateral PNT delivery.
Number of participants completing 12 month study visit
Total number of participants to complete study visit by arm assignment
Study-related adverse events as assessed by MedDRA v27
Total number of study-related adverse events experienced by participants.
Study-related serious adverse events as assessed by MedDRA v.27
Total number of serious adverse events experienced by participants
PNT deployment attempts
Number of deployment attempts required, per participant, to deliver bilateral PNT by group allocation
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.
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.
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.
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Craig van Horne, MD, PhD
Lead sponsor
University of Kentucky
Sponsor institution
National Institute on Aging (NIA)
Collaborator
