DBS and Levodopa for Treating Freezing of Gait in Parkinson's Disease

Официальное название

Efficacy of Deep Brain Stimulation and Levodopa on Freezing of Gait in Advanced Parkinson's Disease: a Comparative Study

Обзор

Freezing of gait (FoG) is a complex symptom of Parkinson's disease (PD) that cause falls and disability in PD patients, heavily affect patients' autonomy and quality of life. Gait disturbances and FoG are difficult to manage as they usually do not complete respond to both dopaminergic treatment and subthalamic nucleus deep brain stimulation (STN-DBS). One therapeutic strategy suggested in literature for improving gait disturbances is to increase the dose of dopaminergic drugs according to the hypothesis of pseudo-ON-freezing. The pseudo-ON-FoG in patients treated with STN-DBS can easily occur as the result of a suboptimal stimulation or the consequence of a post-operative reduction of the dopaminergic therapy. Therefore, it is reasonable hypothesize both the increase of stimulation and levodopa as good therapeutic strategies to improve pseudo-ON-FoG. At present there are no evidence for suppose that one option is better than the other, even though two recent studies on gait analysis reported a positive additive effect of levodopa therapy on gait parameters in patients treated with STN-DBS. In this study, the investigators aim to objectively evaluating the improvement of FoG in PD patients treated with STN-DBS at different treatment conditions consisting of increased intensity of stimulation or higher dosage of levodopa.

Подробное описание

This is a cross-over, blind, randomized study to evaluate the improvement of FoG in a group of PD patients treated with bilateral STN-DBS by increasing the intensity of stimulation (STIM plus) or administering a higher dose of levodopa (MED plus).

Patient will be videorecorded for evaluation of freezing episodes and gait cinematic parameters by means of 3 wearable inertial sensors on the feet and at lumbar level during a standardized walking protocol including: Timed Up and Go, Turn 360°, Gait 18 m and a Complex task in single task and dual task (serial-3 subtractions) conditions. In each condition, Tinetti scale, Trail Making Test, alternate fluency test, Movement Disorders Society Unified Parkinson's disease Rating Scale (MDS-UPDRS) and MDS Unified Dyskinesia Rating Scale (UDysRS) will be also perform.

In addition, other demographic and clinical information such as age, sex, MMSE, MoCA, New Freezing of Gait Questionnaire, Falls Efficacy Scale will be collected.

The primary endpoint of this study is to investigate the efficacy of increasing intensity of stimulation (STIM plus) or levodopa (MED plus) on freezing of gait (FOG).

Secondary outcome measures include cinematic gait parameters, global motor outcomes and cognitive functions.

Вмешательства

• Устройство STIM ON plus
  increase of intensity of stimulation of 0.5 mA bilaterally
• Препарат MED ON plus
  administration of a 2x levodopa morning dose

Первичные конечные точки

• Time spent with FOG during protocol [Срок оценки: immediate post monitoring]

Вторичные конечные точки (5)

• Gait performance [Срок оценки: immediate post monitoring]
• MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III [Срок оценки: immediate post monitoring]
• Patient global impression of change (PGI-C) [Срок оценки: immediate post monitoring]
• Trail Making test A and B [Срок оценки: immediate post monitoring]
• Phonemic/Semantic alternate Fluency test [Срок оценки: immediate post monitoring]

Критерии участия

Критерии включения

• Patients with Parkinson's disease treated with STN-DBS who achieved a good control of motor fluctuations and cardinal motor symptoms (bradykinesia, rigidity, tremor)
• History of FoG in daily-ON condition after optimal DBS programming, defined by a score of 1 on Question 1 and score ≥ 2 on Question 2 of the New Freezing of Gait Questionnaire.

Критерии исключения

• inability to walk independently for 10 meters.
• limited therapeutic windows of stimulation without the possibility of increase the intensity of stimulation of 0,5 mA for the appearance of side effects
• previous evidence of severe adverse effects with high levodopa dose ore increased STN-DBS intensity, such as psychosis, hallucinations, painful dyskinesias, severe hypotension, digestive symptoms.
• dementia (MMSE score ≤ 18)

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Италия · 1 центр

• IRCCS Istituto delle Scienze Neurologiche di Bologna — Bologna

Идентификаторы

NCT: NCT06316232 · DBS-FOG 2023

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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