search
Back to results

Repetitive Transcranial Magnetic Stimulation in Patients With Opioid Use Disorders

Primary Purpose

Transcranial Magnetic Stimulation, Heroin Dependence

Status
Unknown status
Phase
Not Applicable
Locations
Taiwan
Study Type
Interventional
Intervention
Active rTMS
Sham rTMS
Sponsored by
National Cheng-Kung University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Transcranial Magnetic Stimulation focused on measuring repetitive transcranial magnetic stimulation, opioid use disorder, craving, functional magnetic resonance imaging, neuropsychological tests

Eligibility Criteria

20 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Signed informed consent by patient or legal representative.
  2. Male or female patient aged ≧20 and ≦65 years.
  3. A diagnosis of OUD according to DSM criteria made by a specialist in psychiatry.
  4. Patient or a reliable caregiver can be expected to ensure acceptable compliance and visit attendance for the duration of the study.

Exclusion Criteria:

  1. Women of childbearing potential, not using adequate contraception as per investigator judgment or not willing to comply with contraception for the duration of the study.
  2. Females who are pregnant or lactation.
  3. Current evidence of an uncontrolled and/or clinically significant medical condition, e.g.,cardiac, hepatic and renal failure that would compromise patient safety or preclude study participation.
  4. History of seizure or epilepsy.
  5. History of neurological diseases or traumatic brain injury.
  6. Suicidal attempts or risks during screen or study period.
  7. Presence of devices, e.g. pace-makers, cochlear prosthesis, neuro-stimulators, magnetic cochlear prosthesis, intraocular metallic fragments.
  8. Patient has received electroconvulsive therapy (ECT) within 4 weeks prior to the first intervention of the double-blinded treatment.

Sites / Locations

  • National Cheng Kung University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Active rTMS treatment

Sham rTMS treatment

Arm Description

The rTMS parameters were as follows: 15Hz frequency, pulse intensity 100% of the rMT, 60 pulses per train, inter train pause of 26 sec, 40 stimulation trains, and 2400 total pulses for a total duration of 20 min. The patients received one rTMS session per day during the first five days of treatment, and then twice a week for the following three weeks, for a total of 11 rTMS sessions.

The rTMS parameters were as follows: 15Hz frequency, pulse intensity 100% of the rMT, 60 pulses per train, inter train pause of 26 sec, 40 stimulation trains, and 2400 total pulses for a total duration of 20 min, with a figure-of-eight sham coil. The patients received one rTMS session per day during the first five days of treatment, and then twice a week for the following three weeks, for a total of 11 rTMS sessions.

Outcomes

Primary Outcome Measures

The treatment retention rate
To compare the treatment retention rate between the active and sham rTMS groups from baseline to endpoint (12 weeks).
The treatment attendance rate
To compare the treatment attendance rate between the active and sham rTMS groups from baseline to endpoint (12 weeks).
Urinary assessment
Urinary morphine examinations will be measured at every visit. The rate of positive urinary morphine tests will be compared between active and sham rTMS groups in 12 weeks of follow up.

Secondary Outcome Measures

fMRI
The fMRI scan will be done at initial screen and at week 5 (after rTMS treatment) with resting-state fMRI and task activation fMRI with an IGT.
Immunological markers
Twenty milliliters of blood will be drawn from each participant. Plasma will be isolated from the whole blood after it has been centrifuged at 3000 g for 15 min at 4℃, and the will be immediately stored at -80℃. Cytokine and BDNF levels will be quantified using an antibody pair assay system (Flexia; BioSource Intl., Camarillo, CA). Sample processing and data analysis will be done according to the manufacturer's instructions. The immunological parameters that we intend to analyze will include TNF-α, CRP, TGF-β1, IL-8, Il-10 and BDNF. The immunological markers will be measured from baseline to endpoint (week 12) in each patient group.
Wechsler Memory Scale - third edition(WMS-III)
WMS-III will be tested at initial screen and at the end of study (week 12) and compared between the active and sham rTMS groups.
Wisconsin Card Sorting Test(WCST)
WCST will be tested at initial screen and at the end of study (week 12) and compared between the active and sham rTMS groups.
Continuous performance tests(CPT)
CPT will be tested at initial screen and at the end of study (week 12) and compared between the active and sham rTMS groups.
Side effect checklist
To compare the side effect profiles using side effect checklist between the active and sham rTMS groups from baseline to endpoint (12 weeks).
Assessment of craving
To compare the severity of craving between the active and sham rTMS groups from baseline to endpoint (12 weeks).
17-item Hamilton Depression Rating Scale (HDRS)
To compare the mood symptoms between the active and sham rTMS groups from baseline to endpoint (12 weeks).
World Health Organization's Quality of Life Assessment-Brief of Taiwan (WHOQOL-BREF TW)
To compare the life quality (using WHOQOL-BREF TW) between the active and sham rTMS groups from baseline to endpoint (12 weeks).
Family APGAR index
To compare the level of family support (using family APGAR index) between the active and sham rTMS groups from baseline to endpoint (12 weeks).
The Opiate Treatment Index (OTI)
To compare the OTI tween the active and sham rTMS groups from baseline to endpoint (12 weeks).
Clinical Global Impressions (CGI)
To compare the CGI tween the active and sham rTMS groups from baseline to endpoint (12 weeks).
Barratt Impulsiveness Scale(BIS)
To compare the BIS tween the active and sham rTMS groups from baseline to endpoint (12 weeks).

Full Information

First Posted
July 11, 2017
Last Updated
September 13, 2020
Sponsor
National Cheng-Kung University Hospital
Collaborators
Ministry of Science and Technology, Taiwan
search

1. Study Identification

Unique Protocol Identification Number
NCT03229642
Brief Title
Repetitive Transcranial Magnetic Stimulation in Patients With Opioid Use Disorders
Official Title
The Effects of Repetitive Transcranial Magnetic Stimulation in Patients With Opioid Use Disorders: Analysis of Clinical Outcomes, Functional Magnetic Resonance Imaging, Biomarkers, and Neuropsychological Tests
Study Type
Interventional

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Unknown status
Study Start Date
August 1, 2017 (Actual)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
December 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National Cheng-Kung University Hospital
Collaborators
Ministry of Science and Technology, Taiwan

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Opioid use disorder (OUD) is prevalent and causes substantial health and social burdens. Although evidence have showed the effectiveness of opioid agonist maintenance therapy in OUD, high drop-out rate and the requirement of continuing use of opioid agonists are the major problems. Therefore, to develop novel treatment for OUD is important. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive method of brain stimulation used to treat a variety of neuropsychiatric disorders. Recent studies showed that there may be potential therapeutic effects in rTMS for addictive disorder, including reducing craving and substance use severity. The underlying mechanisms of rTMS in treating addictions may involve increased dopamine function in corticomesolimbic brain circuits and modulation of neural activity in brain circuits that relevant to addiction. However, the treatment results of rTMS in OUD were lacked, and the analysis in functional brain imaging study, neuropsychological tests and other potential biomarkers under rTMS treatment were limited, too. Thus, the investigators will conduct the add-on double-blinded, sham-controlled study rTMS treatment in 40-60 patients with OUD under methadone maintenance therapy. Patients will be allocated to active and sham rTMS in a 1 : 1 ratio, and participants will receive rTMS on the left dorsolateral prefrontal cortex (DLPFC) (15 Hz frequency, 4 seconds per train, inter-train interval of 26 seconds, 40 trains per session, total 11 sessions in 4 weeks). The treatment response, urine drug tests, craving scales and side effects to evaluate the therapeutic effects of rTMS will be examined. Neuropsychological assessments, functional magnetic resonance imaging (fMRI) and tests for potential biomarkers of immune parameters will also be measured during 12-weeks follow up. The study results will provide the important data in whether rTMS add-on methadone maintenance therapy is able to 1) reduce heroin use; 2) reduce craving for heroin; 3) be an effective treatment for OUD, and 4) be associated with improvement in fMRI, biological markers and psychological tests.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Transcranial Magnetic Stimulation, Heroin Dependence
Keywords
repetitive transcranial magnetic stimulation, opioid use disorder, craving, functional magnetic resonance imaging, neuropsychological tests

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active rTMS treatment
Arm Type
Experimental
Arm Description
The rTMS parameters were as follows: 15Hz frequency, pulse intensity 100% of the rMT, 60 pulses per train, inter train pause of 26 sec, 40 stimulation trains, and 2400 total pulses for a total duration of 20 min. The patients received one rTMS session per day during the first five days of treatment, and then twice a week for the following three weeks, for a total of 11 rTMS sessions.
Arm Title
Sham rTMS treatment
Arm Type
Sham Comparator
Arm Description
The rTMS parameters were as follows: 15Hz frequency, pulse intensity 100% of the rMT, 60 pulses per train, inter train pause of 26 sec, 40 stimulation trains, and 2400 total pulses for a total duration of 20 min, with a figure-of-eight sham coil. The patients received one rTMS session per day during the first five days of treatment, and then twice a week for the following three weeks, for a total of 11 rTMS sessions.
Intervention Type
Device
Intervention Name(s)
Active rTMS
Intervention Description
The stimulator device was a Magstim super rapid magnetic stimulator (Magstim Company, Ltd., Wales, United Kingdom) with 4 booster modules equipped with a 70-mm air-cooled figure-eight-shaped coil. We performed rTMS on the left dorsolateral prefrontal cortex (DLPFC).The TMS parameters were as follows: 15Hz frequency, pulse intensity 100% of the rMT, 60 pulses per train, inter train pause of 26 sec, 40 stimulation trains, and 2400 total pulses for a total duration of 20 min. The patients received one rTMS session per day during the first five days of treatment, and then twice a week for the following three weeks, for a total of 11 rTMS sessions. The sham group was administered rTMS with the same parameters, but using a figure-of-eight sham coil.
Intervention Type
Device
Intervention Name(s)
Sham rTMS
Intervention Description
The stimulator device was a Magstim super rapid magnetic stimulator (Magstim Company, Ltd., Wales, United Kingdom) with 4 booster modules equipped with a 70-mm air-cooled figure-eight-shaped coil. We performed rTMS on the left dorsolateral prefrontal cortex (DLPFC).The TMS parameters were as follows: 15Hz frequency, pulse intensity 100% of the rMT, 60 pulses per train, inter train pause of 26 sec, 40 stimulation trains, and 2400 total pulses for a total duration of 20 min. The patients received one rTMS session per day during the first five days of treatment, and then twice a week for the following three weeks, for a total of 11 rTMS sessions. The sham group was administered rTMS with the same parameters, but using a figure-of-eight sham coil.
Primary Outcome Measure Information:
Title
The treatment retention rate
Description
To compare the treatment retention rate between the active and sham rTMS groups from baseline to endpoint (12 weeks).
Time Frame
12 weeks
Title
The treatment attendance rate
Description
To compare the treatment attendance rate between the active and sham rTMS groups from baseline to endpoint (12 weeks).
Time Frame
12 weeks
Title
Urinary assessment
Description
Urinary morphine examinations will be measured at every visit. The rate of positive urinary morphine tests will be compared between active and sham rTMS groups in 12 weeks of follow up.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
fMRI
Description
The fMRI scan will be done at initial screen and at week 5 (after rTMS treatment) with resting-state fMRI and task activation fMRI with an IGT.
Time Frame
5 weeks
Title
Immunological markers
Description
Twenty milliliters of blood will be drawn from each participant. Plasma will be isolated from the whole blood after it has been centrifuged at 3000 g for 15 min at 4℃, and the will be immediately stored at -80℃. Cytokine and BDNF levels will be quantified using an antibody pair assay system (Flexia; BioSource Intl., Camarillo, CA). Sample processing and data analysis will be done according to the manufacturer's instructions. The immunological parameters that we intend to analyze will include TNF-α, CRP, TGF-β1, IL-8, Il-10 and BDNF. The immunological markers will be measured from baseline to endpoint (week 12) in each patient group.
Time Frame
12 weeks
Title
Wechsler Memory Scale - third edition(WMS-III)
Description
WMS-III will be tested at initial screen and at the end of study (week 12) and compared between the active and sham rTMS groups.
Time Frame
12 weeks
Title
Wisconsin Card Sorting Test(WCST)
Description
WCST will be tested at initial screen and at the end of study (week 12) and compared between the active and sham rTMS groups.
Time Frame
12 weeks
Title
Continuous performance tests(CPT)
Description
CPT will be tested at initial screen and at the end of study (week 12) and compared between the active and sham rTMS groups.
Time Frame
12 weeks
Title
Side effect checklist
Description
To compare the side effect profiles using side effect checklist between the active and sham rTMS groups from baseline to endpoint (12 weeks).
Time Frame
12 weeks
Title
Assessment of craving
Description
To compare the severity of craving between the active and sham rTMS groups from baseline to endpoint (12 weeks).
Time Frame
12 weeks
Title
17-item Hamilton Depression Rating Scale (HDRS)
Description
To compare the mood symptoms between the active and sham rTMS groups from baseline to endpoint (12 weeks).
Time Frame
12 weeks
Title
World Health Organization's Quality of Life Assessment-Brief of Taiwan (WHOQOL-BREF TW)
Description
To compare the life quality (using WHOQOL-BREF TW) between the active and sham rTMS groups from baseline to endpoint (12 weeks).
Time Frame
12 weeks
Title
Family APGAR index
Description
To compare the level of family support (using family APGAR index) between the active and sham rTMS groups from baseline to endpoint (12 weeks).
Time Frame
12 weeks
Title
The Opiate Treatment Index (OTI)
Description
To compare the OTI tween the active and sham rTMS groups from baseline to endpoint (12 weeks).
Time Frame
12 weeks
Title
Clinical Global Impressions (CGI)
Description
To compare the CGI tween the active and sham rTMS groups from baseline to endpoint (12 weeks).
Time Frame
12 weeks
Title
Barratt Impulsiveness Scale(BIS)
Description
To compare the BIS tween the active and sham rTMS groups from baseline to endpoint (12 weeks).
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed informed consent by patient or legal representative. Male or female patient aged ≧20 and ≦65 years. A diagnosis of OUD according to DSM criteria made by a specialist in psychiatry. Patient or a reliable caregiver can be expected to ensure acceptable compliance and visit attendance for the duration of the study. Exclusion Criteria: Women of childbearing potential, not using adequate contraception as per investigator judgment or not willing to comply with contraception for the duration of the study. Females who are pregnant or lactation. Current evidence of an uncontrolled and/or clinically significant medical condition, e.g.,cardiac, hepatic and renal failure that would compromise patient safety or preclude study participation. History of seizure or epilepsy. History of neurological diseases or traumatic brain injury. Suicidal attempts or risks during screen or study period. Presence of devices, e.g. pace-makers, cochlear prosthesis, neuro-stimulators, magnetic cochlear prosthesis, intraocular metallic fragments. Patient has received electroconvulsive therapy (ECT) within 4 weeks prior to the first intervention of the double-blinded treatment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tzu-Yun Wang
Phone
+886-6-2353535
Ext
5940
Email
tzuyun0105@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tzu-Yun Wang
Organizational Affiliation
National Cheng-Kung University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Cheng Kung University Hospital
City
Tainan
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tzu-Yun Wang
Phone
+886-6-235-3535
Ext
4200
Email
tzuyun0105@hotmail.com
First Name & Middle Initial & Last Name & Degree
Tzu-Yun Wang

12. IPD Sharing Statement

Citations:
PubMed Identifier
33426970
Citation
Tsai TY, Wang TY, Liu YC, Lee PW, Chang WH, Lu TH, Tseng HH, Lee SY, Chang YH, Yang Y, Chen PS, Chen KC, Yang YK, Lu RB. Add-on repetitive transcranial magnetic stimulation in patients with opioid use disorder undergoing methadone maintenance therapy. Am J Drug Alcohol Abuse. 2021 May 4;47(3):330-343. doi: 10.1080/00952990.2020.1849247. Epub 2021 Jan 10.
Results Reference
derived

Learn more about this trial

Repetitive Transcranial Magnetic Stimulation in Patients With Opioid Use Disorders

We'll reach out to this number within 24 hrs