Efficacy and Influencing Factors of ALIC-NAc Deep Brain Stimulation in Treatment-Refractory Obsessive-Compulsive Disorder

Официальное название

Efficacy and Influencing Factors of Combined Anterior Limb of Internal Capsule and Nucleus Accumbens Deep Brain Stimulation in Treatment-Refractory Obsessive-Compulsive Disorder

Обзор

The goal of this clinical trial is to evaluate the efficacy and influencing factors of the combination of the anterior limb of internal capsule and nucleus accumbens (ALIC-NAc) deep brain stimulation (DBS) in patients with treatment-refractory obsessive-compulsive disorder (OCD). The main questions it aims to answer is: Does the timing of DBS activation (at 1, 2, or 3 months post-surgery) affect the reduction rate in Y-BOCS scores? Researchers will compare three groups-DBS activated at 1, 2, and 3 months post-surgery-to determine whether earlier or later stimulation leads to greater symptom improvement. Participants will: * Undergo surgical implantation of an intracranial neurostimulation system targeting ALIC-NAc * Be randomly assigned to one of three DBS activation timing groups * Receive regular clinical assessments over a 6-month follow-up period after activation

Подробное описание

This trial adopted a prospective, multicenter, randomized, open-label, parallel-group design. The study population comprised patients with treatment-refractory obsessive-compulsive disorder whose symptoms could not be effectively controlled by pharmacotherapy and psychotherapy. After providing informed consent, participants underwent implantation of an intracranial neurostimulation system, followed by scheduled activation of stimulation post-surgery.

A total of 60 patients were planned for enrollment and randomly assigned to one of three groups based on the timing of stimulation initiation: the one-month group (activation at 30 ± 7 days post-surgery), the two-month group (activation at 60 ± 7 days), and the three-month group (activation at 90 ± 7 days), with 20 participants in each group (1:1:1 allocation). Participants followed the trial schedule for regular assessments. The primary outcome was the difference in Y-BOCS reduction rates among the three groups at 90 ± 7 days after stimulation initiation.

Вмешательства

• Устройство deep brain stimulation
  Deep Brain Stimulation (DBS) involves the use of stereotactic techniques to implant microelectrodes into specific target nuclei within the brain through minimally invasive surgery. These electrodes are connected via leads to a subcutaneously implanted pulse generator, typically placed beneath the clavicle. By delivering low-intensity electrical pulses, DBS suppresses abnormal intracranial neural activity, thereby alleviating symptoms. Long-term stimulation can also induce neuroplastic changes in

Первичные конечные точки

• Obsessive-compulsive symptoms improvement [Срок оценки: 3-month after DBS activation]

Вторичные конечные точки (4)

• the change scores of CGI score [Срок оценки: 1, 2 and 3-month after DBS activation]
• the change scores of HAMD score [Срок оценки: 1, 2 and 3-month after DBS activation]
• the change scores of HAMA score [Срок оценки: 1, 2 and 3-month after DBS activation]
• the change of SF-36 score [Срок оценки: 1, 2 and 3-month after DBS activation]

Критерии участия

Критерии включения

• aged 18-65 years old;
• a diagnosis of OCD based on The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5);
• the Y-BOCS total score ≥ 25;
• met the criteria of treatment refractory. Treatment refractory is defined as failed a) Inadequate response or intolerance to at least three adequate trials of selective serotonin reuptake inhibitors (SSRIs), combined with at least two second-generation antipsychotics as augmentation agents.

b) Inadequate response or intolerance to cognitive behavioral therapy (CBT) consisting of more than 12 sessions conducted concurrently with adequate dosed SSRIs treatment.

Критерии исключения

• Presence of other psychiatric disorders such as organic mental disorders, paranoid personality disorder, or mental retardation.
• Individuals deemed by the investigator to be at significant risk of suicidal behavior based on clinical assessment.
• Presence of severe or unstable cardiovascular, respiratory, hepatic, renal, hematologic, endocrine, neurological, or other systemic diseases.
• History of organic brain disorders, traumatic brain injury, intractable epilepsy, or other neurological conditions.
• Clinically significant abnormalities in physical examination, laboratory tests, electrocardiogram, or imaging during screening or baseline that, in the investigator's judgment, make the individual unsuitable for the study.
• History of implantation of a cochlear implant, cardiac pacemaker, cardiac defibrillator, prior unilateral or bilateral implantation of similar devices, or other surgical procedures within the past six months that may affect study participation as judged by the investigator.
• Contraindications to DBS implantation or deemed unfit for surgery by the investigator.
• Confirmed HIV-positive status.
• Pregnant or breastfeeding women, women of childbearing potential with positive blood/urine HCG results at screening, those unable to use effective contraception during the study, or those planning to conceive within three months after study initiation.
• Participation in another drug or medical device clinical trial currently or within three months prior to screening.
• Any other condition deemed by the investigator to render the individual unsuitable for the study.

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

Открытое

Основная цель

Лечение

Центры проведения

Китай · 10 центров

• First Affiliated Hospital of Jinan University — Гуанчжоу
• The First Hospital of Hebei Medical University — Shijiazhuang
• The Second Affiliated Hospital of Xinxiang Medical College — Xinxiang
• The First Affiliated Hospital of Nanchang University — Nanchang
• The First Affiliated Hospital of Shanxi Medical University — Taiyuan
• the Third Hospital of Mianyang — Mianyang
• Shanghai Mental Health Center — Шанхай
• Huashan Hospital — Шанхай
• … и ещё 2 центра

Публикации

• Deuschl G, Herzog J, Kleiner-Fisman G, Kubu C, Lozano AM, Lyons KE, Rodriguez-Oroz MC, Tamma F, Troster AI, Vitek JL, Volkmann J, Voon V. Deep brain stimulation: postoperative issues. Mov Disord. 2006 Jun;21 Suppl 14:S219-37. doi: 10.1002/mds.20957. PMID 16810719
• Huys D, Kohl S, Baldermann JC, Timmermann L, Sturm V, Visser-Vandewalle V, Kuhn J. Open-label trial of anterior limb of internal capsule-nucleus accumbens deep brain stimulation for obsessive-compulsive disorder: insights gained. J Neurol Neurosurg Psychiatry. 2019 Jul;90(7):805-812. doi: 10.1136/jnnp-2018-318996. Epub 2019 Feb 15. PMID 30770458
• Denys D, Mantione M, Figee M, van den Munckhof P, Koerselman F, Westenberg H, Bosch A, Schuurman R. Deep brain stimulation of the nucleus accumbens for treatment-refractory obsessive-compulsive disorder. Arch Gen Psychiatry. 2010 Oct;67(10):1061-8. doi: 10.1001/archgenpsychiatry.2010.122. PMID 20921122
• Belotto-Silva C, Diniz JB, Malavazzi DM, Valerio C, Fossaluza V, Borcato S, Seixas AA, Morelli D, Miguel EC, Shavitt RG. Group cognitive-behavioral therapy versus selective serotonin reuptake inhibitors for obsessive-compulsive disorder: a practical clinical trial. J Anxiety Disord. 2012 Jan;26(1):25-31. doi: 10.1016/j.janxdis.2011.08.008. Epub 2011 Aug 19. PMID 21907540
• Soomro GM, Altman D, Rajagopal S, Oakley-Browne M. Selective serotonin re-uptake inhibitors (SSRIs) versus placebo for obsessive compulsive disorder (OCD). Cochrane Database Syst Rev. 2008 Jan 23;2008(1):CD001765. doi: 10.1002/14651858.CD001765.pub3. PMID 18253995
• Huang Y, Wang Y, Wang H, Liu Z, Yu X, Yan J, Yu Y, Kou C, Xu X, Lu J, Wang Z, He S, Xu Y, He Y, Li T, Guo W, Tian H, Xu G, Xu X, Ma Y, Wang L, Wang L, Yan Y, Wang B, Xiao S, Zhou L, Li L, Tan L, Zhang T, Ma C, Li Q, Ding H, Geng H, Jia F, Shi J, Wang S, Zhang N, Du X, Du X, Wu Y. Prevalence of mental disorders in China: a cross-sectional epidemiological study. Lancet Psychiatry. 2019 Mar;6(3):211- PMID 30792114
• Kwon JS, Jang JH, Choi JS, Kang DH. Neuroimaging in obsessive-compulsive disorder. Expert Rev Neurother. 2009 Feb;9(2):255-69. doi: 10.1586/14737175.9.2.255. PMID 19210199
• Boedhoe PSW, Schmaal L, Abe Y, Alonso P, Ameis SH, Anticevic A, Arnold PD, Batistuzzo MC, Benedetti F, Beucke JC, Bollettini I, Bose A, Brem S, Calvo A, Calvo R, Cheng Y, Cho KIK, Ciullo V, Dallaspezia S, Denys D, Feusner JD, Fitzgerald KD, Fouche JP, Fridgeirsson EA, Gruner P, Hanna GL, Hibar DP, Hoexter MQ, Hu H, Huyser C, Jahanshad N, James A, Kathmann N, Kaufmann C, Koch K, Kwon JS, Lazaro L, PMID 29377733

Идентификаторы

NCT: NCT07031544 · SMHC-DBS-003

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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