Characterization of the Involvement of the Subthalamic Nucleus During Wakefulness and Sleep in Parkinson's Disease: Contribution of Deep Brain Stimulation

Обзор

Sleep-wake disturbances are common in Parkinson's disease. These disturbances are associated with a decline in patients' quality of life and a poor prognosis. This clinical research project follows a study conducted in non-human primates that began in 2017 at the Grenoble Institute of Neuroscience. In this study, the investigators confirmed the existence of sleep-wake behavior disturbances in the macaque model of the disease, and the investigators characterized their nature and expression. These disturbances were founded to be very similar to those observed in patients with Parkinson's disease. The investigators then explored the involvement of different brain structures, potentially targets for deep brain stimulation, in sleep-wake behavior under healthy conditions and dopamine depletion (Parkinson's disease model). Among the deep brain stimulation targets being explored, the subthalamic nucleus (STN), still under investigation in this preclinical program, is a promising candidate for deep brain stimulation because this nucleus is strongly implicated in motor behavior and, more recently, in sleep/wake behavior. An ongoing study in non-human primates shows that it is possible to identify states of alertness based on STN activity, and an automatic detection algorithm is currently being evaluated. Furthermore, this study will allow for the characterization of sleep/wake behavioral disturbances (diurnal and nocturnal) in patients with Parkinson's disease. Finally, this study will enable a correlation analysis between disease severity and sleep/wake disturbances.

Подробное описание

The subthalamic nucleus (STN) is a central structure of the basal ganglia circuit. Through its connection to the frontal cortex via the hyperdirect pathway, it is a key indicator of cortical activity, and its stimulation can exert an anterograde influence on the cortex. While the mechanisms of STN deep brain stimulation (DBS) are not yet fully understood, recent studies (see above) have demonstrated that Parkinson's disease (PD) patients with STN implants experience improved sleep. However, this improvement is insufficient to restore more physiological sleep, and further research is needed to develop better management strategies for sleep disorders. In this study, the investigators hypothesize that:

1\) STN activity reflects cortical activity and can therefore detect events characteristic of sleep-wake disorders. 2) Such events detected on the basis of STN activity could allow for a better understanding of the role of the STN in sleep and the development of adaptive DBS targeting sleep disorders in addition to motor disorders.

This is a prospective, single-center, open-label pilot study. Patients with Parkinson's disease for whom surgery to implant deep brain stimulation electrodes in the subthalamic nucleus is indicated will be included. These patients will be recruited by the investigators during their follow-up visits to the neurosurgery department of Grenoble Alpes University Hospital.

In addition to providing a better understanding of how deep brain stimulation of the subthalamic nucleus impacts sleep/wake behavior, this study will allow for a more precise investigation of the subthalamic nucleus's involvement in the pathophysiology of sleep/wake behavior disorders in patients with Parkinson's disease. These results could then lead to the development of adaptive stimulation, triggered according to markers of sleep and wakefulness disorders.

Вмешательства

• Процедура Deep Brain Stimulation
  Subthalamic nucleus stimulation

Первичные конечные точки

• Identification of specific electrophysiological markers of different sleep stages [Срок оценки: 1 year]
• Identification of sleep disorders based on the activity of the subthalamic nucleus [Срок оценки: 1 year]

Вторичные конечные точки (3)

• Characterization of the sleep/wake behavioral disturbances (daytime and nighttime) of the patient with Parkinson's disease [Срок оценки: 1 year]
• Characterization of the sleep/wake behavioral disturbances (nighttime) of the patient with Parkinson's disease [Срок оценки: 1 year]
• Characterization of the sleep/wake behavioral disturbances (daytime) of the patient with Parkinson's disease [Срок оценки: 1 year]

Критерии участия

Критерии включения

• Adult patients with Parkinson's disease, followed at Grenoble University Hospital, for whom surgery to implant deep brain stimulation electrodes in the subthalamic nucleus is indicated
• Patients agreeing to be implanted with a Medtronic PERCEPT stimulator (routine care)
• Patients who have given and signed informed consent
• Patients covered by social security or a similar scheme

Критерии исключения

• Individuals who do not understand/speak French (prevents completion of questionnaires)
• Any condition that, in the investigator's opinion, will prevent the participant from successfully or safely completing the study procedures (i.e., dementia, severe depression, etc.)
• Subjects on exclusion from another study
• Protected persons (Articles L1121-5 to L1121-8 of the French Public Health Code)

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Другое

Центры проведения

Франция · 1 центр

• Neurosurgery Department — Grenoble

Публикации

• Nambu A. Somatotopic organization of the primate Basal Ganglia. Front Neuroanat. 2011 Apr 20;5:26. doi: 10.3389/fnana.2011.00026. eCollection 2011. PMID 21541304
• Baker KB, Montgomery EB Jr, Rezai AR, Burgess R, Luders HO. Subthalamic nucleus deep brain stimulus evoked potentials: physiological and therapeutic implications. Mov Disord. 2002 Sep;17(5):969-83. doi: 10.1002/mds.10206. PMID 12360546
• Devergnas A, Wichmann T. Cortical potentials evoked by deep brain stimulation in the subthalamic area. Front Syst Neurosci. 2011 May 13;5:30. doi: 10.3389/fnsys.2011.00030. eCollection 2011. PMID 21625611
• Davin A, Chabardes S, Devergnas A, Benstaali C, Gutekunst CN, David O, Torres-Martinez N, Piallat B. Excessive daytime sleepiness in a model of Parkinson's disease improved by low-frequency stimulation of the pedunculopontine nucleus. NPJ Parkinsons Dis. 2023 Jan 25;9(1):9. doi: 10.1038/s41531-023-00455-7. PMID 36697421

Идентификаторы

NCT: NCT07637955 · 38RC23.0223 · 2025-A00783-46

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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