Clinical trial NCT06683365: Autologous suraL nervE Grafting to the Substantia nigrA in Patients With Synuclienopathies
Official title: A Phase I Study of the Feasibility and Safety of SuraL nervE Tissue Grafting to the Substantia nigrA in Patients With Synucleinopathies (LEAP)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Multiple System Atrophy
Parkinsons Disease
Keywords: Synucleinopathies
Cell and Tissue Based Therapy
Multiple System Atrophy
Parkinsons Disease
Lead sponsor: University of Kentucky
Sponsor class: OTHER
Collaborators: name: University of Kentucky CCTS
First posted: 2024-11-12
Enrollment: 7
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of clinically established or clinically probable PD or MSA as defined by MDS criteria
* Disease duration greater than 2 years
* Age 40-75, inclusive
* MDS-Unified Parkinson's Disease Rating Scale (UPDRS) Part III greater than or equal to 20 points but less than or equal to 35 points, off anti-parkinsonian medication for PD or MDS-Unified Multiple System Atrophy Rating Scale (UMSARS) less than or equal to 30 points off anti-parkinsonian medication
* No MDS-UPDRS Part III score \>3 on items 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.14 while off medication
* 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:

* Previous PD surgery or intracranial surgery
* Ongoing major medical or psychiatric disorder incl. depression and psychosis
* Other concomitant treatment with neuroleptics
* Typical, nonparkinsonian syndrome ioflupane/SPECT signal
* Unable to undergo an MRI
* An obstructed trajectory path to the substantia nigra
* Significant microvascular disease
* Use of anticoagulants other than aspirin
* Female who is pregnant, lactating, or of child-bearing potential unwilling to use an adequate birth control method during the period of the study
* Consent capacity will be assessed and determined during and throughout a participant's neuropsychological exam. A participant who experiences a decline in consent capacity prior to surgery, will be removed from the study by the PI. A decline in consent capacity after surgery will not result in the removal of the participant in the study.

Primary outcomes:
measure: Meet recruitment goal
timeFrame: Trial opening through 12 months
Secondary outcomes:
measure: Study-related serious adverse events as assessed by MedDRA v.27
timeFrame: Enrollment through 12 months
measure: Study-related adverse events as assessed by MedDRA v27
timeFrame: Enrollment through 6 month study visit
measure: Number of deployment attempts required to deliver bilateral PNT
timeFrame: During the procedure
measure: Duration of procedure
timeFrame: During the procedure
measure: Length of hospital admission
timeFrame: Admission for the procedure through hospital discharge
measure: Percent of study visit completed by participants
timeFrame: Enrollement through 12 month study visit
measure: Change in Neuropsychological diagnosis
timeFrame: Baseline and 12 months
measure: Mean change in Neuropsychological assessment scores
timeFrame: Baseline to 12 months
measure: Mean change in Montreal Cognitive Assessment (MoCA) scores
timeFrame: Baseline, 4 weeks, 6 months, and 12 months
measure: Mean change of the Movement Disorder Society - Unified Parkinsons Disease Rating Scale (MDS-UPDRS) Part I scores
timeFrame: 4 weeks, 6 and 12 months as compared to baseline
measure: Mean change of the MDS-UPDRS Part II scores
timeFrame: 4 weeks, 6 months, and 12 months compared to baseline
measure: Mean change in MDS-UPDRS Part III scores
timeFrame: 4 weeks, 6 and 12 months compared to baseline
measure: Mean change in MDS-UPDRS Part IV scores
timeFrame: 4 weeks, 6 and 12 months compared to baseline
measure: Mean change of the Movement Disorder Society - Unified Multiple System Atrophy Rating Scale (MDS-UMSARS) Part I scores
timeFrame: 4 weeks, 6 and 12 months as compared to baseline
measure: Mean change of the MDS-UMSARS Part II scores
timeFrame: 4 weeks, 6 months, and 12 months compared to baseline
measure: Mean change in MDS-UMSARS Part III scores
timeFrame: 4 weeks, 6 and 12 months compared to baseline
measure: Mean change in MDS-UMSARS Part IV scores
timeFrame: 4 weeks, 6 and 12 months compared to baseline
measure: Mean change in Parkinson's Disease Questionnaire-8 (PDQ-8) quality of life scores
timeFrame: Monthly through 12 month study visit compared to baseline
measure: Mean change in Modified Schwab and England Scale of Activities of Daily Living scores
timeFrame: At 6 and 12 months compared to baseline
measure: Mean change in Non-motor symptom scale scores
timeFrame: Baseline and 12 months
measure: Participants electing to receive Deep Brain Stimulator (DBS)
timeFrame: Enrollment through 12 month study visit
Other outcomes:
Locations:
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.