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NCT Number: NCT06457230

Cerebellum-Prefrontal Paired-Pulse Stimulation for Methamphetamine Use Disorder

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.

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Key information

Conditions

Methamphetamine Use Disorder

Age range

18 year–60 year

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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.

Exclusion criteria

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.

Treatment and study plan

Paired Associative Stimulation Targeting the Cerebellar-mPFC

Device

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.

Sham Intervention over cerebellum and mPFC

Device

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.

Sham stimulation over the cerebellum + real stimulation over the medial prefrontal cortex

Device

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.

Primary outcomes

  1. Craving

    Time frame: before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.

    The intensity of psychological craving in MA dependents was assessed using the Visual Analogue Scale (VAS), where individuals rated their cravings on a scale from 0 to 100, with higher scores indicating greater levels of craving.

  2. cognitive flexibility

    Time frame: Probabilistic reversal learning task and volatile reversal learning task : baseline, post-intervention, and at a follow-up session one week later;

    Based on tasks and scales assessing cognitive flexibility, including: 1.Probabilistic reversal learning task (The matching of symbols and pictures was reversed without informing the subjects and their cognitive flexibility in the reversed condition was assessed); 2.Volatile reversal learning task (participants were presented with two stimuli associated with their potential feedback magnitude. They were instructed to choose one of the two stimuli to receive feedback, but only one stimulus would result in feedback. ).

Secondary outcomes

  1. Other craving scales

    Time frame: before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.

    1、Desires for drug questionnaire (DDQ) consists of 13 items designed to assess an individual's current thoughts and preoccupations related to drug use. 2、Obsessive Compulsive Drug Use Scale (OCDUS)consists of 13 items designed to assess an individual's current thoughts and preoccupations related to drug use.

  2. Electroencephalographic (EEG) Electrophysiological Results

    Time frame: before the intervention (baseline) and immediately after the intervention (post-intervention).

    This includes analyses of TMS-EEG, resting-state EEG, and task-state EEG data across temporal, frequency, and time-frequency domains.

  3. response inhibition

    Time frame: SST task: baseline, post-intervention, and at a follow-up session one weeks later.

    The Stop-Signal Task (SST) is a seminal experimental paradigm in cognitive psychology and neuroscience designed to objectively measure an individual's response inhibition-the ability to actively suppress a prepotent or already-initiated motor response. To gain a more comprehensive understanding of an individual's inhibitory control, it is highly informative to complement this with a trait-based, self-reported measure of impulsivity.

  4. Depression

    Time frame: before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.

    The reduction rate of Beck Depression Inventory (BDI) scores was calculated from baseline to post-intervention and follow-up assessments to quantify the decrease in depressive symptom severity.

  5. Anxiety

    Time frame: before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.

    The reduction rate in the Beck Anxiety Inventory (BAI) scores was calculated from baseline to post-intervention and follow-up assessments to quantify the decrease in anxiety symptom severity.

  6. sleep quality

    Time frame: before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.

    The reduction rate of Pittsburgh Sleep Quality Index (PSQI) global scores was calculated from baseline to post-intervention and follow-up assessments to quantify the improvement in sleep quality.

Study contacts

Contact information is provided by the study sponsor or research team.

64387250 Zhao, PhD

CONTACT

[email protected]

64387250

Min Zhao, PhD

CONTACT

[email protected]

64387250

Sponsors and collaborators

Lead sponsor

Shanghai Mental Health Center

Other

Collaborators

  • Chengdu Drug Rehabilitation Center
  • HanYang Comoulsory Isolation Drug Rehabilitation Center, Wuhan
  • Mental Health Center, West China Hospital of Sichuan University, Chengdu
  • Sichuan Ziyang Compulsory Isolation Drug Rehabilitation Center
  • Wuhan Mental Health Center, The Ninth Clinical School, Tongji Medical College, Huazhong University of Science and Technology, Wuhan

Registry information

Official study title

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

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Jun 13, 2024
Registry last updated
Jun 24, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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