Subthalamic Nucleus Versus Globus Pallidal Internus Deep Brain Stimulation for Parkinson Disease

Обзор

The primary objective of this prospective, multicenter, double-blind, randomized, crossover clinical trial is to evaluate whether Subthalamic Nucleus-Deep Brain Stimulation (STN-DBS) is more effective than Globus Pallidus Internus-Deep Brain Stimulation (GPi-DBS) in improving motor symptoms of patients with Parkinson's disease at 90 days post-treatment.

Подробное описание

The primary objective of this prospective, multicenter, double-blind, randomized crossover controlled clinical trial is to evaluate whether STN-DBS provides superior efficacy over GPi-DBS in improving motor symptoms of Parkinson's disease patients at 90 days post-treatment.

Randomization of this study is generated by a centralized Contract Research Organization (CRO). At the second follow-up visit, patients will be assigned according to the randomization code list in the system, with each patient first receiving either STN-DBS or GPi-DBS. The randomization ratio between the two groups is 1:1. At the third follow-up visit, each group will then receive stimulation at the other target.

Assessments of motor function, cognitive level, anxiety and depression status, and quality of life will be conducted preoperatively. The device will be activated 30 days postoperatively. Target adjustments, along with assessments of motor function, cognitive level, anxiety and depression status, quality of life, and adverse events, will be performed at 120, 210, and 300 days postoperatively.

The grouping information will only be known to the operating surgeons and programming physicians, while other investigators, assessing physicians, and patients will remain blinded. This study will be completed within 24 months, enrolling 86 patients from 7 centers in China, with 43 patients in each group. The Data Safety Monitoring Board (DSMB) will conduct regular monitoring to ensure the safe conduct of the study.

Вмешательства

• Устройство STN-DBS stimulation
  The devices for this study are provided by Boston Scientific International Medical Trading (Shanghai) Co., Ltd.The system consists of two components: electrodes and an implanted stimulator.Participants will be implanted with an 8-contact directional electrode (Model: DB-2202-45).The stimulator is a rechargeable model (Model: DB-1232). Participants will receive the STN target stimulation protocol for a 3-month treatment period.
• Устройство GPi-DBS stimulation
  The devices for this study are provided by Boston Scientific International Medical Trading (Shanghai) Co., Ltd.The system consists of two components: electrodes and an implanted stimulator.Participants will be implanted with an 8-contact directional electrode (Model: DB-2202-45).The stimulator is a rechargeable model (Model: DB-1232). Participants will receive the GPi target stimulation protocol for a 3-month treatment period.
• Устройство STN&GPi-DBS stimulation
  The devices for this study are provided by Boston Scientific International Medical Trading (Shanghai) Co., Ltd.The system consists of two components: electrodes and an implanted stimulator.Participants will be implanted with an 8-contact directional electrode (Model: DB-2202-45).The stimulator is a rechargeable model (Model: DB-1232). After participants receive 3 months of STN target monotherapy and 3 months of GPi target monotherapy sequentially, they will be administered the combined STN + GP

Первичные конечные точки

• Unified Parkinson's Disease Rating Scale Part III (UPDRS III) score [Срок оценки: Before surgery and 90 days (±7 days) after surgery]

Вторичные конечные точки (11)

• Freezing of Gait Questionnaire (FOG-Q) score [Срок оценки: Before surgery and 90 days (±7 days) after surgery]
• Berg Balance Scale (BBS) score [Срок оценки: Before surgery and 90 days (±7 days) after surgery]
• Unified Dyskinesia Rating Scale (UDysRS) score [Срок оценки: Before surgery and 90 days (±7 days) after surgery]
• Mini-Mental State Examination (MMSE) score [Срок оценки: Before surgery and 90 days (±7 days) after surgery]
• Montreal Cognitive Assessment (MoCA) score [Срок оценки: Before surgery and 90 days (±7 days) after surgery]
• Hamilton Anxiety Rating Scale (HAMA) score [Срок оценки: Before surgery and 90 days (±7 days) after surgery]
• Hamilton Rating Scale for Depression (HRSD) score [Срок оценки: Before surgery and 90 days (±7 days) after surgery]
• Parkinson's Disease Questionnaire-39 (PDQ-39) score [Срок оценки: Before surgery and 90 days (±7 days) after surgery]
• Programming parameters [Срок оценки: 90 days (±7 days) after surgery]
• Differences in programming parameters and medication under combined stimulation [Срок оценки: Baseline and 90 days (±7 days) after surgery]
• Patient preference for stimulation targets [Срок оценки: 90 days (±7 days) after surgery]

Критерии участия

Критерии включения

• Age at the time of enrollment: 22-75 years.
• Diagnosis of bilateral idiopathic PD with the presence of at least 2 of the following: resting tremor, rigidity, or bradykinesia
• Duration of idiopathic PD: ≥ 5 years.
• Severity of PD in the meds off condition: Hoehn-Yahr stages 2.5\~ 4.0.
• Despite optimal medication treatment, there are still persistent symptoms or drug side effects of disabling Parkinson's
• Must have tried a form of carbidopa/levodopa and/or one of the dopamine agonists as part of medication therapy.
• Anti-parkinsonian medications must improve PD symptoms by ≥33%, as measured by UPDRS-III score.
• UPDRS-III score of ≥ 30 in the meds off condition.
• The MMSE assessment was higher than the demarcation score of the corresponding educational level, and the cognitive function was normal.
• HAMD score≤24.
• No change in antidepressant medications utilized for treatment of depression for at least 8 weeks prior to informed consent.
• Stable on anti-parkinsonian medication for 28 days prior to informed consent.
• Could tolerate bilateral STN DBS and bilateral GPi DBS.
• Be willing and able to comply with all visits and study related procedures (e.g., using the remote control, charging system and completing the PD Diary
• Able to understand the study requirements and the treatment procedures and provides written informed consent before any studyspecific tests or procedures are performed.

Критерии исключения

• Any intracranial abnormalities or medical conditions that Lead to the prohibition of DBS surgery.
• Have any significant psychiatric condition likely to compromise the subject's ability to comply with requirements of the study protocol (e.g. bipolar, schizophrenia, mood disorder with psychotic features, cluster B personality disorders).
• HAMD score>24.
• Any current drug or alcohol abuse, per DSM-IV criteria
• Any history of recurrent or unprovoked seizures.
• Any history of hemorrhagic stroke.
• Any previous treatment for movement disorders involving intracranial surgery or device implantation.
• Any other active implanted devices including neurostimulators (e.g., cochlear implant, pacemaker) and /or drug delivery pumps, whether turned on or off. Passive implants (e.g., knee prostheses) would be allowed provided that they do not interfere with the functioning of the DBS system
• Any previous thalamotomy, pallidotomy or subjects who have undergone a DBS procedure.
• Any previously implanted Vagus Nerve Stimulation (VNS) patients.
• Any previous brain surgery that would interfere with the placement of the leads or the functioning of the device.
• A condition requiring or likely to require the use of Magnetic Resonance Imaging (MRI), diathermy or electroconvulsive therapy (ECT)
• Likely to require the use of monopolar cau Likely to require the use of monopolar cautery, radiofrequency (RF) procedures, external defibrillation, lithotripsy, radiation therapy or transcranial stimulation.tery, radiofrequency (RF) procedures, external defibrillation, lithotripsy, radiation therapy or transcranial stimulation.
• Currently on any anticoagulant medications that cannot be discontinued during perioperative period.
• Currently exhibiting secondary Parkinsonism due to prescribed medications.
• Have any significant medical condition that is likely to interfere with study procedures or likely to confound evaluation of study endpoints.
• Any terminal illness with life expectancy of < 1 year.
• Any unresolved infection, a coagulopathy or significant cardiac or other medical risk factor for surgery
• Current or future risk of being immunocompromised that might significantly increase risk of infection.
• Participation in any other clinical trial (e.g. drug, device, or biologics) concurrently or within the preceding 30 days. Participation in any other study will be allowed per investigator/sponsor discretion only.
• A female who is breastfeeding or of child-bearing potential with a positive urine pregnancy test or not using adequate contraception.
• Preoperative DBS plan failed to implant STN and GPi. nuclei.(Usually limited by individual anatomical differences)
• Preoperative CT scan of the head revealed calcification of the GPI.

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

Двойное слепое

Основная цель

Лечение

Центры проведения

Китай · 8 центров

• Beijing Tiantan Hospital Affiliated to Capital Medical University — Пекин
• Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and — Ухань
• Nanjing Brain Hospital — Нанкин
• The First Affiliated Hospital of Dalian Medical University — Dalian
• Qilu Hospital of Shandong University — Цзинань
• Changhai Hospital of Shanghai — Шанхай
• Tianjin Huanhu Hospital — Тяньцзинь
• The Second Affiliated Hospital of Zhejiang University School of Medicine — Ханчжоу

Публикации

• Sidiropoulos C, LeWitt PA, Odekerken VJ, Schuurman PR, de Bie RM. GPi vs STN deep brain stimulation for Parkinson disease: Three-year follow-up. Neurology. 2016 Aug 16;87(7):745-6. doi: 10.1212/WNL.0000000000003027. No abstract available. PMID 27527541
• Xu H, Zheng F, Krischek B, Ding W, Xiong C, Wang X, Niu C. Subthalamic nucleus and globus pallidus internus stimulation for the treatment of Parkinson's disease: A systematic review. J Int Med Res. 2017 Oct;45(5):1602-1612. doi: 10.1177/0300060517708102. Epub 2017 Jul 12. PMID 28701061
• Dulski J, Schinwelski M, Konkel A, Grabowski K, Libionka W, Waz P, Sitek EJ, Slawek J. The impact of subthalamic deep brain stimulation on sleep and other non-motor symptoms in Parkinson's disease. Parkinsonism Relat Disord. 2019 Jul;64:138-144. doi: 10.1016/j.parkreldis.2019.04.001. Epub 2019 Apr 5. PMID 30975618
• Ramirez-Zamora A, Ostrem JL. Globus Pallidus Interna or Subthalamic Nucleus Deep Brain Stimulation for Parkinson Disease: A Review. JAMA Neurol. 2018 Mar 1;75(3):367-372. doi: 10.1001/jamaneurol.2017.4321. PMID 29356826
• Okun MS. Deep-brain stimulation--entering the era of human neural-network modulation. N Engl J Med. 2014 Oct 9;371(15):1369-73. doi: 10.1056/NEJMp1408779. Epub 2014 Sep 8. No abstract available. PMID 25197963
• Chen J, Liu JL, Chen X, Qian H, Xian WB, Zhou HY, Liu YM, Ye XF, Zheng YF, Zhang SL, Chen L, Li JR, Liu ZL, Pei Z. [Significant improvement of motor symptoms by deep brain stimulation of bilateral subthalamic nucleus in patients with moderate or advanced Parkinson's disease]. Zhonghua Yi Xue Za Zhi. 2011 Feb 1;91(5):291-5. Chinese. PMID 21419000
• Nova IC, Perracini MR, Ferraz HB. Levodopa effect upon functional balance of Parkinson's disease patients. Parkinsonism Relat Disord. 2004 Oct;10(7):411-5. doi: 10.1016/j.parkreldis.2004.04.004. PMID 15465397
• Bejjani BP, Gervais D, Arnulf I, Papadopoulos S, Demeret S, Bonnet AM, Cornu P, Damier P, Agid Y. Axial parkinsonian symptoms can be improved: the role of levodopa and bilateral subthalamic stimulation. J Neurol Neurosurg Psychiatry. 2000 May;68(5):595-600. doi: 10.1136/jnnp.68.5.595. PMID 10766889

Идентификаторы

NCT: NCT07250685 · HX-A-2025009

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗