Autologous suraL nervE Grafting to the Substantia nigrA in Patients With Synuclienopathies

NCT06683365 | Recruiting Phase 1

• 2 other identifiers: 95534UL1TR001998
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple System Atrophy; Parkinsons Disease

Keywords

Synucleinopathies; Cell and Tissue Based Therapy; Multiple System Atrophy; Parkinsons Disease

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (21)

• Study-related serious adverse events as assessed by MedDRA v.27

  Enrollment through 12 months

• Study-related adverse events as assessed by MedDRA v27

  Enrollment through 6 month study visit

• Number of deployment attempts required to deliver bilateral PNT

  During the procedure

• Duration of procedure

  During the procedure

• Length of hospital admission

  Admission for the procedure through hospital discharge

Study Arms (2)

Nerve Graft Recipients

EXPERIMENTAL

Procedure: Sural Nerve Graft to the Substantia Nigra

Placebo Group

PLACEBO COMPARATOR

Procedure: Sham surgery

Interventions

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.

Placebo Group

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.

Nerve Graft Recipients

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Craig van Horne, MD, PhD: lead
• University of Kentucky CCTS: collaborator
• National Center for Advancing Translational Sciences (NCATS): collaborator

Study Sites (1)

University of Kentucky

Lexington, Kentucky, 40536, United States

RECRUITING

Related Publications (3)

• 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.

  PMID: 35949912 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.

  PMID: 27153166 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.

  PMID: 29451447 RESULT

MeSH Terms

Conditions

Multiple System Atrophy; Parkinson Disease; Synucleinopathies

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Neurodegenerative Diseases; Parkinsonian Disorders; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Craig van Horne, MD, PhD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jaimie Hixson

CONTACT

859-323-1908; jaimie.henderson@uky.edu

Group Monitored Email

CONTACT

nervegraft@uky.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 7, 2024
• First Posted: November 12, 2024
• Study Start: February 25, 2025
• Primary Completion (Estimated): December 2, 2028
• Study Completion (Estimated): December 2, 2030
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (1)