Paired-pulse rTMS Treatment for Methamphetamine Use Disorder Based on the mPFC-Cerebellum

NCT ID: NCT06457230

Last Updated: 2025-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-12-24

Study Completion Date

2026-08-31

Brief Summary

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

Detailed Description

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Numerous studies have shown that impaired mPFC-cerebellar 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 reduce relapse risk. The aim of this project is to investigate the mechanism and efficacy of a novel paired-pulse rTMS intervention targeting the mPFC-cerebellar 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 cerebellar-mPFC circuit connectivity compared to healthy controls. Importantly, cerebellar-mPFC ccPAS with a 6-ms ISI was found to specifically modulate this inter-regional circuit dysfunction.

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.

Conditions

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Methamphetamine Use Disorder

Keywords

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Repetitive transcranial magnetic stimulation Cerebellum Frontopolar cortex Methamphetamine Cortico-Cortical Paired Associative Stimulation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Sham Cerebellar Stimulation + Sham mPFC Stimulation Group

This is the sham stimulation group. 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.

Group Type SHAM_COMPARATOR

Sham Intervention Group

Intervention Type 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.

Cerebellar-mPFC Dual-Coil Paired-Pulse TMS Intervention Group

The stimulation protocol involved delivering a pulse to the cerebellum first, followed by a pulse to the mPFC after a 6ms inter-stimulus interval (ISI). This 6ms interval was determined based on findings from our prior mechanistic study.

Group Type EXPERIMENTAL

Paired Associative Stimulation Targeting the Cerebellar-mPFC

Intervention Type 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.

Interventions

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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.

Intervention Type DEVICE

Sham Intervention Group

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.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

1. Primary substance of abuse is methamphetamine.
2. Meets the DSM-5 diagnostic criteria for severe methamphetamine use disorder (≥6 symptoms present within the past year).
3. Age: 18-60 years.
4. Education level of primary school or above, with the ability to comprehend questionnaires and behavioral tasks.
5. Normal vision and hearing; right-handed.
6. No prior participation in any TMS-related intervention therapy.

Exclusion Criteria

1. Presence of any metallic implants (e.g., dental prostheses, orthodontic braces, bone fixation plates, aneurysm clips, intrauterine devices) or implanted medical devices such as cardiac pacemakers or neurostimulators.
2. Chronic or severe somatic diseases (e.g., cardiac conditions, uncontrolled hypertension, physical disabilities).
3. Comorbid psychiatric disorders (e.g., schizophrenia, depressive disorders, anxiety disorders).
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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Hanyang Drug Rehabilitation Center

UNKNOWN

Sponsor Role collaborator

Chengdu Drug Rehabilitation Center

UNKNOWN

Sponsor Role collaborator

Shanghai Mental Health Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Min Zhao, PhD

Role: STUDY_CHAIR

Shanghai Mental Health Center

Locations

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Min Zhao, PhD

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Min Zhao, PhD

Role: CONTACT

Phone: 64387250

Email: [email protected]

64387250 Zhao, PhD

Role: CONTACT

Phone: 64387250

Email: [email protected]

Facility Contacts

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Min Zhao, PhD

Role: primary

Min Zhao, PhD

Role: backup

Other Identifiers

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MZhao-015

Identifier Type: -

Identifier Source: org_study_id