Cerebellum-Prefrontal Paired-Pulse Stimulation for Methamphetamine Use Disorder

Официальное название

Exploring the Mechanisms and Efficacy of Cerebellum-Medial Prefrontal Cortex-Based Paired-Pulse Repetitive Transcranial Magnetic Stimulation for Methamphetamine Use Disorder

Обзор

To investigate the mechanism and efficacy of a novel repetitive transcranial magnetic stimulation (rTMS) intervention model with paired cerebellar-medial prefrontal cortex (mPFC) pulses on methamphetamine use disorder patients and to develop a novel physiotherapeutic intervention to optimise the treatment and management.

Подробное описание

Numerous studies have shown that impaired cerebellar- mPFC functional connectivity leads to impaired social preferences and behavioural flexibility and more persistent drug use in addicts. Cerebellar and mPFC paired-pulse rTMS interventions may enhance functional connectivity, effectively modulate cerebellar-prefrontal loops, reduce craving, improve cognitive flexibility, and modulate cortical excitability. The aim of this project is to investigate the mechanism and efficacy of a novel paired-pulse rTMS intervention targeting the cerebellar-mPFC circuit in patients with methamphetamine use disorder, in order to develop innovative physiotherapeutic interventions and to optimize treatment and clinical management for individuals with addiction.

Prior to initiating the intervention, it was essential to determine the optimal inter-stimulus interval (ISI) for the cerebellar-mPFC paired associative stimulation. Therefore, a mechanistic study was conducted from December 2024 to June 2025 at the Chengdu Drug Rehabilitation Center in Sichuan Province before the interventional trial commenced. A mixed design was employed, contrasting single-pulse mPFC stimulation with cerebellum→mPFC cortico-cortical paired associative stimulation (ccPAS) at inter-stimulus intervals of 6 ms and 45 ms. The results revealed that individuals with methamphetamine use disorder exhibited aberrant mPFC cortical excitability compared to healthy controls. Importantly, cerebellar-mPFC ccPAS with a 6-ms ISI was found to specifically modulate mPFC cortical excitability.

Therefore, based on the identified 6-ms cerebellar-mPFC stimulation interval, the current interventional study continues to implement a long-term, dual-coil combined stimulation protocol to further evaluate and establish its therapeutic efficacy.

Вмешательства

• Устройство Paired Associative Stimulation Targeting the Cerebellar-mPFC
  The protocol consisted of 180 pulse trains. Each train contained 5 pulse pairs delivered over 1 second, resulting in a stimulation frequency of 5 Hz. Within each pulse pair, the cerebellum was stimulated first, followed by the mPFC after a 6-ms inter-stimulus interval (ISI). In total, 900 pulse pairs were administered, and a complete intervention session lasted 11 minutes and 57 seconds.
• Устройство Sham Intervention over cerebellum and mPFC
  The coil will be placed vertically over the cerebellar and mPFC brain regions, allowing participants to perceive the coil's vibration and sound without receiving effective intervention. All other stimulation parameters are identical to those in the active intervention group.
• Устройство Sham stimulation over the cerebellum + real stimulation over the medial prefrontal cortex
  Participants in this group will receive sham stimulation over the cerebellum (The coil will be placed vertically over the cerebellum) combined with real stimulation over the medial prefrontal cortex.

Первичные конечные точки

• Craving [Срок оценки: before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.]
• cognitive flexibility [Срок оценки: Probabilistic reversal learning task and volatile reversal learning task : baseline, post-intervention, and at a follow-up session one week later;]

Вторичные конечные точки (6)

• Other craving scales [Срок оценки: before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.]
• Electroencephalographic (EEG) Electrophysiological Results [Срок оценки: before the intervention (baseline) and immediately after the intervention (post-intervention).]
• response inhibition [Срок оценки: SST task: baseline, post-intervention, and at a follow-up session one weeks later.]
• Depression [Срок оценки: before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.]
• Anxiety [Срок оценки: before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.]
• sleep quality [Срок оценки: before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.]

Критерии участия

Критерии включения

Participants will be eligible for inclusion if they meet the following criteria:

• Methamphetamine is the primary substance of use, and the participant meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for moderate or severe methamphetamine use disorder;
• aged 18 to 60 years;
• normal or corrected-to-normal vision and hearing, and right-handedness;
• primary school education or above, with the ability to understand the questionnaires and behavioral task instructions.

Критерии исключения

Participants will be excluded if they meet any of the following criteria:

• presence of metal objects in the body, such as metal dentures, orthodontic braces, bone fixation plates, aneurysm clips, or other metallic implants;
• severe physical illness or chronic disease, including heart disease, severe hypertension, stroke, epilepsy, or history of head trauma;
• comorbid psychiatric disorders, such as bipolar disorder, schizophrenia, or severe depression;
• previous participation in transcranial magnetic stimulation- or electroencephalography-related studies;
• refusal to participate in the study, poor compliance, or any other contraindications to transcranial magnetic stimulation.

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

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Min Zhao, PhD — Шанхай

Идентификаторы

NCT: NCT06457230 · MZhao-015 · 2021ZD0202105 · 2024YFF0507604 · 82130041, 82471510, U25C2016

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗