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

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

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.

Study Overview

• Status: Unknown
• Conditions: Relapse; Heroin Addiction
• Intervention / Treatment: Device: Repetitive transcranial magnetic stimulation

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710038
      • Tangdu Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Active repetitive transcranial magnetic stimulation	Device: Repetitive transcranial magnetic stimulation; 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)
SHAM_COMPARATOR: Sham repetitive transcranial magnetic stimulation	Device: Repetitive transcranial magnetic stimulation; 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)
NO_INTERVENTION: No repetitive transcranial magnetic stimulation

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Tang-Du Hospital
• Investigators: Principal Investigator: Longxiao Wei, phd, Tang-Du Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2019
• Primary Completion (ANTICIPATED): July 1, 2021
• Study Completion (ANTICIPATED): July 1, 2022

Study Registration Dates

• First Submitted: September 2, 2019
• First Submitted That Met QC Criteria: September 9, 2019
• First Posted (ACTUAL): September 11, 2019

Study Record Updates

• Last Update Posted (ACTUAL): January 22, 2021
• Last Update Submitted That Met QC Criteria: January 20, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Functional magnetic resonance imaging; Repetitive transcranial magnetic stimulation; Positron emission tomography
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Compulsive Behavior; Impulsive Behavior; Opioid-Related Disorders; Heroin Dependence; Behavior, Addictive
• Other Study ID Numbers: Addiction-No.1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No