Parkinson's Disease
Conditions
Keywords
Parkinson's Disease, Deep Brain Stimulation, DBS, Cell and Tissue Based Therapy
Brief summary
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.
Interventions
PROCEDUREReparative Autologous peripheral nerve tissue
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 nucleus basalis of Meynert (NBM) or substantia nigra (SN).
Sponsors
Craig van Horne, MD, PhD
National Institute on Aging (NIA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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 * 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 * Dementia diagnosis * Previous PD surgery or intracranial surgery * Unable to undergo an MRI * An obstructed trajectory path to the substantia nigra and nucleus basalis of Meynert
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Successful deployment of bilateral peripheral nerve tissue (PNT) into the brain | Intraoperative | Number of participants in each study arm who successfully receive bilateral PNT delivery. |
| Number of participants completing 12 month study visit | 12-month study visit | Total number of participants to complete study visit by arm assignment |
| Study-related adverse events as assessed by MedDRA v27 | Enrollment to 24-month study visit | Total number of study-related adverse events experienced by participants. |
| Study-related serious adverse events as assessed by MedDRA v.27 | Enrollment to 24-month study visit | Total number of serious adverse events experienced by participants |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean change of the MDS-UPDRS Part II scores | At 6, 12, 24 months compared to baseline | MDS-UPDRS Part II scores motor symptoms effecting activities of daily living in those with Parkinson's Disease. Scores range from 0-52 with higher scores indicating greater symptom severity. |
| Mean change in MDS-UPDRS Part III scores | At 6, 12, 24 months compared to baseline | MDS-UPDRS Part III scores motor symptoms associated with Parkinson's Disease. Part III scores range from 0-132 with higher scores indicating higher symptom severity. |
| Mean change in MDS-UPDRS Part IV scores | At 6, 12, and 24 months compared to baseline | MDS-UPDRS Part IV scores motor complications such as fluctuations and dyskinesia's associated with anti-Parkinson's medications. Scores range from 0-24 with higher scores indicating greater severity in motor complications. |
| Number of participants completing 24-month study visit | 24-month study visit | Total number of participants completing 24 month study visit by group allocation |
| Mean change in Dementia Rating Scale (DSRS) | Baseline 6, 12 and 24 months after surgery | A survey to assess and rate changes the cognitive and behavioral functioning of participants. Scale is scored from 0-54 with being higher numbers indicating greater dementia severity. |
| Change in Neuropsychological domains with impairment | At 12, 24 months compared to baseline | A count of the number of domains with impairment at each study visit to compare with previous study visits. |
| PNT deployment attempts | During surgery | Number of deployment attempts required, per participant, to deliver bilateral PNT by group allocation |
| Mean change in Montreal Cognitive Assessment (MoCA) scores | Baseline 6, 12 and 24 months after surgery | 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 | Baseline, 12 and 24 months | 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. |
| Mean change in Modified Schwab and England Scale of Activities of Daily Living scores | At 6, 12, 24 months compared to baseline | Mean change participant independence levels as measured in Schwab and England Scale of Activities of Daily Living scores. 100% = completed independent and 0% being completely dependent. |
| Change in Neuropsychological diagnosis | Baseline, 12 and 24 months | Changes in participant neuropsychological diagnoses during scheduled evaluations will be reported. e.g. No cognitive diagnosis progressing to mild neurocognitive disorder. |
| Mean change in Parkinson's Disease Questionnaire-8 (PDQ-8) quality of life scores | At 12 and 24 months compared to baseline | Assess changes in participant's quality of life. Questionnaire is scored from 0-32 with higher scores indicating poorer quality of life. |
| Mean change in Non-motor symptom scale scores | At 12 and 24 months compared to baseline | Assessment used to identify Parkinson's disease related non-motor symptoms experienced by participants. The scale measures the frequency and severity of symptoms and is scored from 0-360 with higher scores indicating more frequent and severe symptoms. |
| Mean change of the Movement Disorder Society - Unified Parkinsons Disease Rating Scale (MDS-UPDRS) Part I scores | 6, 12, and 24 months as compared to baseline | MDS-UPDRS Part I scores non-motor symptoms effecting activities of daily living in those with Parkinson's Disease. Scores range from 0-52 with higher scores indicating greater symptom severity. |
Countries
United States
Contacts
CONTACTJaimie Hixson
CONTACTGroup Monitored Email
PRINCIPAL_INVESTIGATORCraig G van Horne, MD, PhD
University of Kentucky
Outcome results
None listed