PET/MRI Study on the Neurological Mechanism of rTMS Treatment for Heroin Addiction

Study Overview
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Brief Summary
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Heroin addiction is a serious problem and the relapse rate of existing treatment methods is extremely high. Recently, international journals such as Science reported that repetitive transcranial magnetic stimulation (rTMS) can reduce the craving of addicts, alleviate depression and anxiety symptoms, and is expected to become an effective treatment. Our preliminary experiment using rTMS to stimulate the left dorsolateral prefrontal cortex of heroin addicts also showed similar effects, however, the mechanism is unclear. Previously, the investigators found that the functional connectivity between left executive control network and default mode network was negatively correlated relapse behavior, while the functional connectivity between salience network and default mode network was positively correlated with relapse behavior. Studies have shown that dopamine dysfunction in addicts and brain metabolism is the biological basis of network connectivity. It suggests that elucidating the relationship between the characteristics of large brain network connectivity and the level of dopamine receptor and relapse behavior in addicts is hopeful to further understand the neurological mechanism of rTMS treatment for addiction. In this project, the investigators intend to observe the changes of brain network connectivity, glucose metabolism and dopamine D2 receptor before and after rTMS treatment in addicts from the perspective of large brain network by combining PET/MRI with psychobehavioral approach. The relationship between rTMS and relapse behavior will be deeply analyzed to provide scientific basis for the development of effective treatment programs.

Official Title
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PET/MRI Study on the Neurological Mechanism of rTMS Treatment for Heroin Addiction by Stimulating Left Dorsolateral Prefrontal Cortex

Conditions
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Heroin Addiction, Relapse

Intervention / Treatment
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* Device: Repetitive transcranial magnetic stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Heroin-dependent Participants: Clinical diagnosis of heroin addiction Have been receiving treatment in a methadone maintenance treatment program for no less than 6 months have been on a stable dose for at least 1 month before entering the study Right-handed Inclusion Criteria for Healthy Control Participants: Clinical diagnosis of Healthy Control Right-handed Exclusion Criteria for all Participants: Current or past psychiatric illness other than heroin and nicotine dependence Neurological signs and/or history of neurological disease History of head trauma History of cardiovascular or endocrine disease Current medical illness or recent medicine use Presence of magnetically active objects in the body Claustrophobia or any other medical condition that would preclude the participant from lying in the PET/MRI scanner for approximately 40 min.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Three groups (two groups of heroin addiction during methadone maintenance treatment and one healthy control group) were included in this study design. One heroin addiction group was administered active repetitive transcranial magnetic stimulation (rTMS) while another heroin addiction group was administered sham. The healthy control group was not given rTMS, just as control.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active repetitive transcranial magnetic stimulation<br> | Device: Repetitive transcranial magnetic stimulation<br>* Those receiving experimental treatment will receive 20 sessions of rTMS, stimulation protocol included 20 sessions within 30 days (once a day, 5 days/week, 4 weeks, 10 Hz frequency, pulse intensity 100% of the resting motor threshold, 50 pulses per train, inter train pause of 10 s, 40 stimulation trains, 2000 pulses/ session)<br>|
| Sham Comparator: Sham repetitive transcranial magnetic stimulation<br> | Device: Repetitive transcranial magnetic stimulation<br>* Those receiving experimental treatment will receive 20 sessions of rTMS, stimulation protocol included 20 sessions within 30 days (once a day, 5 days/week, 4 weeks, 10 Hz frequency, pulse intensity 100% of the resting motor threshold, 50 pulses per train, inter train pause of 10 s, 40 stimulation trains, 2000 pulses/ session)<br>|
| No Intervention: No repetitive transcranial magnetic stimulation<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of craving | Craving scores will be assessed with visual analogue scale | Baseline, 1 week later, 1,2,3,4,5,6 months later | 
| Change of protracted-abstinence symptoms | Protracted-abstinence symptoms scores will be assessed with protracted symptoms questionnaire | Baseline, 1 week later, 1,2,3,4,5,6 months later | 
| Change of depress symptoms | Depress symptoms scores will be assessed with Beck Depression Inventory | Baseline, 1 week later, 1,2,3,4,5,6 months later | 
| Change of anxiety symptoms | Anxiety symptoms scores will be assessed with Hamilton Anxiety Scale | Baseline, 1 week later, 1,2,3,4,5,6 months later | 
| Change of impulsive behaviors | Impulsive behaviors scores will be assessed with Barratt impulsiveness scale | Baseline, 1 week later, 1,2,3,4,5,6 months later | 
| Change of sleep | Sleep scores will be assessed with Pittsburgh sleep quality index | Baseline, 1 week later, 1,2,3,4,5,6 months later | 
| Change of functional connectivity between dorsolateral prefrontal cortex and whole brain | Functional connectivity based on dorsolateral prefrontal cortex will be measured with magnetic resonance imaging based on blood oxygen level dependence | Baseline, 1 week later, 1,3,6 months later | 
| Change of gray matter volume of whole brain | Gray matter volume will be measured with magnetic resonance imaging (high resolution T1-weighted image) | Baseline, 1 week later, 1,3,6 months later | 
| Change of white matter integrity of whole brain | Fractional anisotropy, axial diffusivity and radial diffusivity will be measured with magnetic resonance imaging (diffusion tensor imaging) | Baseline, 1 week later, 1,3,6 months later | 
| Change of availability of dopamine 2 receptor of whole brain | Accumulation of 11C-raclopride will be analyzed by time-related Positron emission tomography | Baseline, 1 month later | 
| Change of metabolism of glucose in the brain | Accumulation of 18F-FDG will be analyzed by time-related Positron emission tomography | Baseline, 1 month later | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Repetitive transcranial magnetic stimulation, Functional magnetic resonance imaging, Positron emission tomography