Methamphetamine Use DisorderNCT06457230
Cerebellum-Prefrontal Paired-Pulse Stimulation for Methamphetamine Use Disorder
A study testing Paired Associative Stimulation Targeting the Cerebellar-mPFC in people with Methamphetamine Use Disorder, run by Shanghai Mental Health Center at 1 site in China.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 60 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Methamphetamine Use Disorder
- What is being tested?
- Paired Associative Stimulation Targeting the Cerebellar-mPFC
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 1 siteChina
- Study dates
- 24 Dec 2024to Sep 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Min Zhao, PhD
Shanghai, Shanghai Municipality, 200000
Min Zhao, PhD, 64387250, drminzhao@gmail.com
Min Zhao, PhD, 18017311005, drminzhao@gmail.com
About this study
Official title: Exploring the Mechanisms and Efficacy of Cerebellum-Medial Prefrontal Cortex-Based Paired-Pulse Repetitive Transcranial Magnetic 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.
Read the detailed description
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.
- Conditions
- Methamphetamine Use Disorder
- Being tested
- Paired Associative Stimulation Targeting the Cerebellar-mPFC, Sham Intervention over cerebellum and mPFC, Sham stimulation over the cerebellum + real stimulation over the medial prefrontal cortex
- Keywords
- Repetitive transcranial magnetic stimulation, Cerebellum, Methamphetamine, Cortico-Cortical Paired Associative Stimulation, medial prefrontal cortex
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Paired Associative Stimulation Targeting the Cerebellar-mPFCDevice
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 mPFCDevice
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 cortexDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Sham Cerebellar Stimulation + Sham mPFC Stimulation Group | Sham comparator | 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. Receives: Device: Sham Intervention over cerebellum and mPFC |
| Cerebellar-mPFC Dual-Coil Paired-Pulse TMS Intervention Group | Experimental | 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. Receives: Device: Paired Associative Stimulation Targeting the Cerebellar-mPFC |
| Cerebellar Sham + Real mPFC Stimulation Group | Active comparator | This group serves as the positive control group for single-site stimulation. Participants in this group will receive real stimulation over the medial prefrontal cortex combined with sham stimulation over the cerebellum. This design allows us to determine whether the therapeutic effects of paired cerebellum-medial prefrontal cortex stimulation are attributable to the paired stimulation protocol itself, rather than to the effect of single-target stimulation of the medial prefrontal cortex alone. Receives: Device: Sham stimulation over the cerebellum + real stimulation over the medial prefrontal cortex |
What is being measured
The primary outcome is the main question the study is designed to answer.
Craving
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.
Measured: before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.
cognitive flexibility
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. ).
Measured: Probabilistic reversal learning task and volatile reversal learning task : baseline, post-intervention, and at a follow-up session one week later;
Secondary outcomes (6)
Other craving scales
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.
Measured: before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.
Electroencephalographic (EEG) Electrophysiological Results
This includes analyses of TMS-EEG, resting-state EEG, and task-state EEG data across temporal, frequency, and time-frequency domains.
Measured: before the intervention (baseline) and immediately after the intervention (post-intervention).
response inhibition
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.
Measured: SST task: baseline, post-intervention, and at a follow-up session one weeks later.
Depression
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.
Measured: before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.
Anxiety
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.
Measured: before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.
sleep quality
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.
Measured: before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2024
- Study start24 Dec 2024
- Primary completionJul 2026 (estimated)
- Study completionSep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Methamphetamine Use DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Mental Health Center
- Sponsor type
- University, hospital or other
- Collaborators
- Chengdu Drug Rehabilitation Center, Sichuan Ziyang Compulsory Isolation Drug Rehabilitation Center, Mental Health Center, West China Hospital of Sichuan University, Chengdu, Wuhan Mental Health Center, The Ninth Clinical School, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HanYang Comoulsory Isolation Drug Rehabilitation Center, Wuhan
- Responsible party
- Sponsor
- Investigators
- Min Zhao, PhD, Study chair, Shanghai Mental Health Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06457230
- Sponsor's protocol ID
- MZhao-015
- Other IDs
- 2021ZD0202105, 2024YFF0507604, 82130041, 82471510, U25C2016
- Status last verified
- Jun 2026
- First submitted
- 10 Jun 2024
- Last updated
- 24 Jun 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after de-identification, will be made available at the discretion of the corresponding author, following a formal request and execution of a data use agreement.
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploring the Mechanisms and Efficacy of Cerebellum-Medial Prefrontal Cortex-Based Paired-Pulse Repetitive Transcranial Magnetic Stimulation for Methamphetamine Use Disorder
- ClinicalTrials.gov ID
- NCT06457230
- Acronym / sponsor ID
- MZhao-015
- Conditions
- Methamphetamine Use Disorder
- Keywords
- Repetitive transcranial magnetic stimulation, Cerebellum, Methamphetamine, Cortico-Cortical Paired Associative Stimulation, medial prefrontal cortex
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Shanghai Mental Health CenterUniversity, hospital or other
- Collaborators
- Chengdu Drug Rehabilitation Center, Sichuan Ziyang Compulsory Isolation Drug Rehabilitation Center, Mental Health Center, West China Hospital of Sichuan University, Chengdu, Wuhan Mental Health Center, The Ninth Clinical School, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HanYang Comoulsory Isolation Drug Rehabilitation Center, Wuhan
- Study start
- 24 Dec 2024 (actual)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Sep 2026 (estimated)
- First posted
- 13 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Sham Cerebellar Stimulation + Sham mPFC Stimulation Group | Sham comparator | Device: Sham Intervention over cerebellum and mPFCThis 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. |
| Cerebellar-mPFC Dual-Coil Paired-Pulse TMS Intervention Group | Experimental | Device: Paired Associative Stimulation Targeting the Cerebellar-mPFCThe 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. |
| Cerebellar Sham + Real mPFC Stimulation Group | Active comparator | Device: Sham stimulation over the cerebellum + real stimulation over the medial prefrontal cortexThis group serves as the positive control group for single-site stimulation. Participants in this group will receive real stimulation over the medial prefrontal cortex combined with sham stimulation over the cerebellum. This design allows us to determine whether the therapeutic effects of paired cerebellum-medial prefrontal cortex stimulation are attributable to the paired stimulation protocol itself, rather than to the effect of single-target stimulation of the medial prefrontal cortex alone. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Paired Associative Stimulation Targeting the Cerebellar-mPFCThe 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. | Device | Cerebellar-mPFC Dual-Coil Paired-Pulse TMS Intervention Group |
| Sham Intervention over cerebellum and mPFCThe 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. | Device | Sham Cerebellar Stimulation + Sham mPFC Stimulation Group |
| Sham stimulation over the cerebellum + real stimulation over the medial prefrontal cortexParticipants 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. | Device | Cerebellar Sham + Real mPFC Stimulation Group |
Primary outcome
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.
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. ).
6 secondary outcomes
Other craving scales
Time frame: before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.
Electroencephalographic (EEG) Electrophysiological Results
Time frame: before the intervention (baseline) and immediately after the intervention (post-intervention).
response inhibition
Time frame: SST task: baseline, post-intervention, and at a follow-up session one weeks later.
Depression
Time frame: before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.
Anxiety
Time frame: before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.
sleep quality
Time frame: before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2026.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after de-identification, will be made available at the discretion of the corresponding author, following a formal request and execution of a data use agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Min Zhao, PhD study chair
Shanghai Mental Health Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Paired Associative Stimulation Targeting the Cerebellar-mPFC in people with Methamphetamine Use Disorder, run by Shanghai Mental Health Center at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Min Zhao, PhD (64387250, drminzhao@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Craving (time frame: before the intervention (baseline), immediately after the intervention (post-intervention), and at a follow-up session one weeks later.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2026.