A Study to Evaluate Feasibility, Safety, and Clinical Responses of Implanting Autologous Peripheral Nerve Tissue Into the Brain for Non-motor or Motor Symptoms in Patients With Parkinson's Disease Undergoing DBS Surgery

Официальное название

Phase I Randomized, Double-blind Study to Evaluate Feasibility, Safety, and Clinical Responses of Implanting Autologous Peripheral Nerve Tissue Into the Nucleus Basalis of Meynert or Substantia Nigra for Non-motor or Motor Symptoms in Patients With Parkinson's Disease Undergoing DBS Surgery

Обзор

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.

Вмешательства

• Процедура Reparative 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 Meyner

Первичные конечные точки

• Successful deployment of bilateral peripheral nerve tissue (PNT) into the brain [Срок оценки: Intraoperative]
• Number of participants completing 12 month study visit [Срок оценки: 12-month study visit]
• Study-related adverse events as assessed by MedDRA v27 [Срок оценки: Enrollment to 24-month study visit]
• Study-related serious adverse events as assessed by MedDRA v.27 [Срок оценки: Enrollment to 24-month study visit]

Вторичные конечные точки (12)

• PNT deployment attempts [Срок оценки: During surgery]
• Mean change in Montreal Cognitive Assessment (MoCA) scores [Срок оценки: Baseline 6, 12 and 24 months after surgery]
• Mean change in Neuropsychological assessment scores [Срок оценки: Baseline, 12 and 24 months]
• Change in Neuropsychological diagnosis [Срок оценки: Baseline, 12 and 24 months]
• Change in Neuropsychological domains with impairment [Срок оценки: At 12, 24 months compared to baseline]
• Mean change in Modified Schwab and England Scale of Activities of Daily Living scores [Срок оценки: At 6, 12, 24 months compared to baseline]
• Mean change in Parkinson's Disease Questionnaire-8 (PDQ-8) quality of life scores [Срок оценки: At 12 and 24 months compared to baseline]
• Mean change in Non-motor symptom scale scores [Срок оценки: At 12 and 24 months compared to baseline]
• Mean change of the Movement Disorder Society - Unified Parkinsons Disease Rating Scale (MDS-UPDRS) Part I scores [Срок оценки: 6, 12, and 24 months as compared to baseline]
• Mean change of the MDS-UPDRS Part II scores [Срок оценки: At 6, 12, 24 months compared to baseline]
• Mean change in MDS-UPDRS Part III scores [Срок оценки: At 6, 12, 24 months compared to baseline]
• Mean change in MDS-UPDRS Part IV scores [Срок оценки: At 6, 12, and 24 months compared to baseline]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of Kentucky — Lexington

Публикации

• Quintero JE, Chau MJ, Slevin JT, Koehl L, Gurwell JA, Wallace E, Kryscio RJ, El Khouli R, Anderson-Mooney AJ, Schmitt FA, Gerhardt GA, van Horne CG. Two-year feasibility and safety of open-label autologous peripheral nerve tissue implantation during deep brain stimulation in patients with Parkinson's disease. J Parkinsons Dis. 2025 Mar;15(2):397-408. doi: 10.1177/1877718X241312409. Epub 2025 Feb 2 PMID 40007169
• 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 2 PMID 29451447
• 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

Идентификаторы

NCT: NCT06683378 · 90066 · 1R01AG081356-01A1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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