Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| UL1TR001998 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| University of Kentucky CCTS | UNKNOWN |
| National Center for Advancing Translational Sciences (NCATS) | NIH |
Not provided
Not provided
Not provided
Not provided
This phase I double-blind study focuses on the safety and feasibility of implanting autologous peripheral nerve tissue (PNT) into the substantia nigra area of the brain in persons who have been diagnosed with either Parkinson's disease (PD) or Multiple System Atrophy (MSA). 7 participants will be enrolled, with 4 participants receiving the graft and 3 receiving a sham surgery. Eligible participants will be early in their diagnosis with a lower burden of symptoms. Participants will be followed initially for one year after surgery.
This phase I double blind clinical trial will be used to plan future, larger clinical trials that would test how autologous cells from the peripheral nerve may help in the repair of damaged brain cells in Parkinson's Disease (PD) or Multiple System Atrophy (MSA) and slow the progression of the diseases. We will be judging the feasibility of implanting a participant's own cells from a nerve in the leg into the substantia nigra area of the brain. Patients eligible for participation will be at an earlier in stage of the disease with symptoms being less severe and therefore would not yet qualify for DBS. The LEAP trial is a study where the first participant will receive an implantation of the cells from their own sural nerve (a nerve near the ankle), into the substantia nigra on both sides of their brain. The 6 participants who follow, will be randomized to one of two arms. The 3 participants assigned to the experimental arm will receive the graft. The 3 participants assigned to the control arm will receive a sham surgical procedure, where the sural nerve will be biopsied, and bilateral scalp incisions will be made. Those who do not receive the cells initially may be eligible to undergo another surgery at the end of the study, after un-blinding has occurred, to receive the cell implants.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nerve Graft Recipients | Experimental |
| |
| Placebo Group | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sural Nerve Graft to the Substantia Nigra | Procedure | Participants assigned to this arm will have the sural nerve biopsied from one of their ankles. This cellular tissue will be deposited bilaterally into the substantia nigra area of their brain by a specialized cannula via bilateral scalp incisions and skull burr holes. |
| Measure | Description | Time Frame |
|---|---|---|
| Meet recruitment goal | Ability to recruit, enroll, and assign participants to the trial within 12 months of the trial opening. | Trial opening through 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Study-related serious adverse events as assessed by MedDRA v.27 | Total number of serious adverse events associated with bilateral PNT collection and deployment to the substantia nigra. Serious adverse events will be defined as an abscess, tumor, infection of the bed of the graft, altered mental state, seizure, ankle or foot infection, wound dehiscence at the ankle incision, spread of neuropathy of the ankle or foot on the ipsilateral side of the nerve biopsy, or other event determined by the PI/investigators to be important. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jaimie Hixson | Contact | 859-323-1908 | jaimie.henderson@uky.edu | |
| Group Monitored Email | Contact | nervegraft@uky.edu |
| Name | Affiliation | Role |
|---|---|---|
| Craig van Horne, MD, PhD | University of Kentucky | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Kentucky | Recruiting | Lexington | Kentucky | 40536 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35949912 | Result | Quintero JE, Slevin JT, Gurwell JA, McLouth CJ, El Khouli R, Chau MJ, Guduru Z, Gerhardt GA, van Horne CG. Direct delivery of an investigational cell therapy in patients with Parkinson's disease: an interim analysis of feasibility and safety of an open-label study using DBS-Plus clinical trial design. BMJ Neurol Open. 2022 Jul 14;4(2):e000301. doi: 10.1136/bmjno-2022-000301. eCollection 2022. | |
| 27153166 | Result | van Horne CG, Quintero JE, Gurwell JA, Wagner RP, Slevin JT, Gerhardt GA. Implantation of autologous peripheral nerve grafts into the substantia nigra of subjects with idiopathic Parkinson's disease treated with bilateral STN DBS: a report of safety and feasibility. J Neurosurg. 2017 Apr;126(4):1140-1147. doi: 10.3171/2016.2.JNS151988. Epub 2016 May 6. |
Not provided
Not provided
Images and results may be made available to other researchers by asking participants, at the time of consent, their willingness to permit sharing of data and bio-specimens.
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D019578 | Multiple System Atrophy |
| D010300 | Parkinson Disease |
| D000080874 | Synucleinopathies |
| ID | Term |
|---|---|
| D054969 | Primary Dysautonomias |
| D001342 | Autonomic Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D001480 | Basal Ganglia Diseases |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Sham surgery | Procedure | Participants assigned to this arm will have the sural nerve from one of their ankles biopsied in the same fashion as the experimental arm. Bilateral incisions will be made on the participants scalp but no burr holes into the skull and no cannula passes into the brain will occur. |
|
| Enrollment through 12 months |
| Study-related adverse events as assessed by MedDRA v27 | Total number of adverse events experienced by participants categorized by System Organ Class and/or High Level Group Term using MedDRA v27 for designation. | Enrollment through 6 month study visit |
| Number of deployment attempts required to deliver bilateral PNT | Per protocol, the surgeon has two chances to successfully deploy 60% of the PNT tissue loaded in the guide-tube into the brain per hemisphere. The number of attempted deployments will be documented and if <60% of the tissue is deployed after two attempts, a failed delivery will be documented and no other attempts will be made. | During the procedure |
| Duration of procedure | Number of minutes it takes for the procedure to be completed. This will be defined by the anesthesia start time and anesthesia end time. | During the procedure |
| Length of hospital admission | The number of days each participant is admitted to the inpatient hospital for the procedure and acute post-operative care. | Admission for the procedure through hospital discharge |
| Percent of study visit completed by participants | The number of designated study visits completed compared to the total number of study visits that are scheduled to occur. | Enrollement through 12 month study visit |
| 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. | Baseline and 12 months |
| Mean change in Neuropsychological assessment scores | Participants complete a neuropsychological assessment battery that meets the 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 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. | Baseline to 12 months |
| 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. | Baseline, 4 weeks, 6 months, and 12 months |
| Mean change of the Movement Disorder Society - Unified Parkinsons Disease Rating Scale (MDS-UPDRS) Part I scores | 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. | 4 weeks, 6 and 12 months as compared to baseline |
| Mean change of the MDS-UPDRS Part II scores | 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. | 4 weeks, 6 months, and 12 months compared to baseline |
| Mean change in MDS-UPDRS Part III scores | 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. | 4 weeks, 6 and 12 months compared to baseline |
| Mean change in MDS-UPDRS Part IV scores | 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. | 4 weeks, 6 and 12 months compared to baseline |
| Mean change of the Movement Disorder Society - Unified Multiple System Atrophy Rating Scale (MDS-UMSARS) Part I scores | MDS-UMSARS Part I rates patient reported functional disabilities. Scores for this section range from 0-48 with higher scores indicating greater disability | 4 weeks, 6 and 12 months as compared to baseline |
| Mean change of the MDS-UMSARS Part II scores | MDS-UMSARS Part II scores motor symptoms associated with multiple system atrophy. Scores range from 0-56 with higher scores indicating greater symptom severity. | 4 weeks, 6 months, and 12 months compared to baseline |
| Mean change in MDS-UMSARS Part III scores | MDS-UMSARS Part III assesses orthostatic hypertension symptoms. This part examines blood pressure changes when a participant stands up after laying down for two minutes. It is scored as either a "Yes" the participant experiences orthostatic hypertension, or a "No" the participant does not don't experience orthostatic hypertension. | 4 weeks, 6 and 12 months compared to baseline |
| Mean change in MDS-UMSARS Part IV scores | MDS-UMSARS Part IV assess the participants global disability. Scores range from 1-5 with 1 being completely independent and 5 being totally dependent/bedridden. | 4 weeks, 6 and 12 months compared to baseline |
| Mean change in Parkinson's Disease Questionnaire-8 (PDQ-8) quality of life scores | Assess changes in participant's quality of life. Questionnaire is scored from 0-32 with higher scores indicating poorer quality of life. | Monthly through 12 month study visit compared to baseline |
| Mean change in Modified Schwab and England Scale of Activities of Daily Living scores | 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. | At 6 and 12 months compared to baseline |
| Mean change in Non-motor symptom scale scores | 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. | Baseline and 12 months |
| Participants electing to receive Deep Brain Stimulator (DBS) | Number of study participants who elect to have DBS implanted prior to completing the 12 month study visit. | Enrollment through 12 month study visit |
| 29451447 | Result | van Horne CG, Quintero JE, Slevin JT, Anderson-Mooney A, Gurwell JA, Welleford AS, Lamm JR, Wagner RP, Gerhardt GA. Peripheral nerve grafts implanted into the substantia nigra in patients with Parkinson's disease during deep brain stimulation surgery: 1-year follow-up study of safety, feasibility, and clinical outcome. J Neurosurg. 2018 Dec 1;129(6):1550-1561. doi: 10.3171/2017.8.JNS163222. Epub 2018 Feb 18. |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009069 | Movement Disorders |
| D019636 | Neurodegenerative Diseases |
| D020734 | Parkinsonian Disorders |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |