评估迷走神经刺激与正念训练联合治疗偏头痛的脑机制：一项随机2×2析因临床试验方案。

Evaluating brain mechanisms of combined vagus nerve stimulation and mindfulness training for migraine: A randomized 2 × 2 factorial clinical trial protocol.

作者信息

Schuman-Olivier Zev, Marin Frances, Kinder Lillian D, Datko Michael, Round Kassandra, Tohyama Sarasa, Garcia Ronald G, Hirschtick Randy L, Edwards Robert R, Wells Rebecca Erwin, Cheng Hsinlin T, Barbieri Riccardo, Hadjikhani Nouchine, Loggia Marco L, Kaptchuk Ted J, Houle Timothy T, Rosen Bruce R, Napadow Vitaly

机构信息

Center for Mindfulness and Compassion, Department of Psychiatry, Cambridge Health Alliance, Harvard Medical School, Cambridge, MA, USA.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA; Center for Mindfulness and Compassion, Department of Psychiatry, Cambridge Health Alliance, Harvard Medical School, Cambridge, MA, USA.

出版信息

Contemp Clin Trials. 2025 Jul;154:107947. doi: 10.1016/j.cct.2025.107947. Epub 2025 May 21.

DOI:10.1016/j.cct.2025.107947

PMID:40409681

Abstract

BACKGROUND

Migraine is a major cause of disability and efficacious interventions are needed. In this mechanistic study, we investigate the combined, and potentially synergistic, effects of a multimodal intervention combining Mindfulness-Based Stress Reduction (MBSR) and transcutaneous auricular Vagal Nerve Stimulation (taVNS) for migraine.

METHODS

We utilize a modified double-blinded, placebo-controlled, 2 × 2 factorial randomized longitudinal design to assess the effects of an 8-week MBSR intervention with concomitant Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) taVNS on migraine pathophysiology primary outcomes. We will enroll 150 patients with migraine (4-20 headache days/month). After a run-in month of daily diaries, we expect to randomly assign N = 96 participants to one of four treatment groups: (1) MBSR+RAVANS taVNS, (2) MBSR+Sham taVNS, (3) Nature Education Control (NEC) + RAVANS taVNS, or (4) NEC + Sham taVNS. Before and after intervention, participants have three in-person assessments (a 7 T MRI scan, an autonomic/sensory testing (AST) visit, and a 3 T PET-MRI scan). The primary outcomes for this study assess (1) central sensitization (brainstem/cortical response to trigeminal sensory afference), (2) autonomic dysfunction (High Frequency-Heart Rate Variability (HF-HRV) response to stressors), and (3) neuroinflammation (PET[C]PBR28 signal).

RESULTS

Funded by NIH (P01AT009965), registered (NCT03592329). Final longitudinal outcomes will be collected by May 2025.

CONCLUSION

This mechanistic study is designed to investigate both independent and synergistic neurobiological effects of MBSR and RAVANS taVNS interventions on three distinct pathophysiological mechanisms of migraine. This research will elucidate the mechanistic and potentially synergistic effects of behavioral interventions (e.g., mindfulness) and device-based treatments (e.g., taVNS) for migraine.

摘要

背景

偏头痛是导致残疾的主要原因，需要有效的干预措施。在这项机制研究中，我们调查了基于正念减压疗法（MBSR）和经皮耳迷走神经刺激（taVNS）的多模式干预对偏头痛的联合作用以及潜在的协同作用。

方法

我们采用改良的双盲、安慰剂对照、2×2析因随机纵向设计，评估为期8周的MBSR干预联合呼吸门控耳迷走神经传入神经刺激（RAVANS）taVNS对偏头痛病理生理学主要结局的影响。我们将招募150名偏头痛患者（每月头痛4 - 20天）。在进行一个月的每日日记记录的导入期后，我们预计将N = 96名参与者随机分配到四个治疗组之一：（1）MBSR + RAVANS taVNS，（2）MBSR + 假taVNS，（3）自然教育对照组（NEC） + RAVANS taVNS，或（4）NEC + 假taVNS。在干预前后，参与者进行三次面对面评估（一次7T磁共振成像扫描、一次自主神经/感觉测试（AST）就诊以及一次3T正电子发射断层扫描 - 磁共振成像扫描）。本研究的主要结局评估：（1）中枢敏化（脑干/皮质对三叉神经感觉传入的反应），（2）自主神经功能障碍（高频心率变异性（HF - HRV）对应激源的反应），以及（3）神经炎症（PET[C]PBR28信号）。