结构和功能磁共振脑生物标志物在精神分裂症患者药物抵抗性幻听 rTMS 治疗中的临床反应：一项随机假刺激对照双盲临床试验研究方案。

Structural and functional brain biomarkers of clinical response to rTMS of medication-resistant auditory hallucinations in schizophrenia patients: study protocol for a randomized sham-controlled double-blind clinical trial.

机构信息

Unité de Recherche Clinique, Établissement Public de Santé Ville-Evrard, 202 avenue Jean Jaurès, 93332, Neuilly-sur-Marne, France.

Cerebral Dynamics, Plasticity and Rehabilitation Group, Frontlab, Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière, CNRS UMR 7225, INSERM UMRS 1127 and Université Pierre et Marie Curie, 47 boulevard de l'Hôpital, 75013, Paris, France.

出版信息

Trials. 2019 Apr 23;20(1):229. doi: 10.1186/s13063-019-3311-x.

DOI:10.1186/s13063-019-3311-x

PMID:31014369

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6480831/

Abstract

BACKGROUND

The potential of non-invasive repetitive transcranial magnetic stimulation (rTMS) to improve auditory verbal hallucinations (AVH) in schizophrenia patients has been increasingly explored over the past decade. Despite highly promising results, high inter-individual variability of clinical response and ineffective outcomes in a significant number of patients underscored the need to identify factors associated with the clinical response to rTMS. It should help improve the efficacy of rTMS in patients with medication-resistant AVH, and allow a better understanding of its neural impact. Here, we describe an exploratory study protocol which aims to identify structural and functional brain biomarkers associated with clinical response after an rTMS treatment for medication-resistant AVH in schizophrenia.

METHODS

Forty-five schizophrenia patients with medication-resistant AVH will be enrolled in a double-blind randomized sham-controlled monocentric clinical trial. Patients will be assigned to a regime of 20 sessions of active or sham 1 Hz rTMS delivered twice a day, 5 days a week for 2 weeks over the left temporo-parietal junction. Response will be assessed after rTMS and patients will be classified in responders or non-responders to treatment. Magnetic resonance imaging (MRI) sessions including diffusion weighted imaging and resting-state functional MRI sequences will be recorded before the onset of the rTMS treatment and 3 days following its discontinuation. The primary outcome measure is difference in fractional anisotropy between responder and non-responder patients at baseline. Differences in resting-state functional MRI data at baseline will be also investigated between responder and non-responder groups. Clinical, neuropsychological, neurophysiological, and blood serum BDNF assessments will be performed at baseline, 3 days, 1 month, and 3 months following rTMS.

DISCUSSION

The aim of this research project is to identify and assess the biomarker value of MRI-based structural and functional biomarkers predicting clinical response to rTMS for AVH in schizophrenia patients. The outcome of the trial should improve patient care by offering them a novel suitable therapy and deepen our understanding on how rTMS may impact AVH and develop more effective therapies adapted to individual patient needs.

TRIAL REGISTRATION

ClinicalTrials.gov, NCT02755623 . Registered on 22 April 2016.

摘要

背景

在过去十年中，非侵入性重复经颅磁刺激（rTMS）改善精神分裂症患者幻听（AVH）的潜力越来越受到关注。尽管结果非常有希望，但由于临床反应的个体间高度差异以及相当数量的患者治疗效果不佳，这凸显了确定与 rTMS 临床反应相关因素的必要性。这将有助于提高 rTMS 在药物抵抗性 AVH 患者中的疗效，并使其对其神经影响有更好的理解。在这里，我们描述了一项探索性研究方案，旨在确定与精神分裂症药物抵抗性 AVH 患者 rTMS 治疗后临床反应相关的结构和功能脑生物标志物。

方法

将招募 45 名患有药物抵抗性 AVH 的精神分裂症患者参加一项双盲随机假对照单中心临床试验。患者将被分配到每天两次、每周 5 天接受 20 次主动或假 1Hz rTMS 的方案中，为期 2 周，刺激部位为左颞顶联合区。rTMS 治疗后进行反应评估，并将患者分为治疗反应者和非反应者。在 rTMS 治疗开始前和治疗停止后 3 天进行磁共振成像（MRI）检查，包括弥散加权成像和静息态功能 MRI 序列。主要观察指标为基线时反应者和非反应者之间各向异性分数的差异。还将在反应者和非反应者组之间研究基线时静息态功能 MRI 数据的差异。在 rTMS 后 3 天、1 个月和 3 个月时进行临床、神经心理学、神经生理学和血清 BDNF 评估。