Transcranial Magnetic StimulationNCT03229642
Repetitive Transcranial Magnetic Stimulation in Patients With Opioid Use Disorders
A study testing Active rTMS in people with Transcranial Magnetic Stimulation and Heroin Dependence, run by National Cheng-Kung University Hospital at 1 site in Taiwan.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 65 years
- Conditions the study is for
- Transcranial Magnetic Stimulation, Heroin Dependence
- What is being tested?
- Active rTMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteTaiwan
- Study dates
- 1 Aug 2017to 31 Dec 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 20 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
National Cheng Kung University Hospital
Tainan
Tzu-Yun Wang, +886-6-235-3535 ext. 4200, tzuyun0105@hotmail.com
Tzu-Yun Wang
About this study
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
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.
- Being tested
- Active rTMS, Sham rTMS
- Keywords
- repetitive transcranial magnetic stimulation, opioid use disorder, craving, functional magnetic resonance imaging, neuropsychological tests
- Medical subject headings
- Heroin Dependence, Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active rTMSDevice
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.
Sham rTMSDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Active rTMS treatment | Experimental | 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. Receives: Device: Active rTMS |
| Sham rTMS treatment | Sham comparator | 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. Receives: Device: Sham rTMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
The treatment retention rate
To compare the treatment retention rate between the active and sham rTMS groups from baseline to endpoint (12 weeks).
Measured: 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).
Measured: 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.
Measured: 12 weeks
Secondary outcomes (13)
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.
Measured: 5 weeks
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.
Measured: 12 weeks
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.
Measured: 12 weeks
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.
Measured: 12 weeks
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.
Measured: 12 weeks
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).
Measured: 12 weeks
Assessment of craving
To compare the severity of craving between the active and sham rTMS groups from baseline to endpoint (12 weeks).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 12 weeks
The Opiate Treatment Index (OTI)
To compare the OTI tween the active and sham rTMS groups from baseline to endpoint (12 weeks).
Measured: 12 weeks
Clinical Global Impressions (CGI)
To compare the CGI tween the active and sham rTMS groups from baseline to endpoint (12 weeks).
Measured: 12 weeks
Barratt Impulsiveness Scale(BIS)
To compare the BIS tween the active and sham rTMS groups from baseline to endpoint (12 weeks).
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2017
- Study start1 Aug 2017
- Primary completion31 Dec 2022 (estimated)
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Transcranial Magnetic StimulationStudies of the same condition, open and under way.
- More trials run by National Cheng-Kung University HospitalThe sponsor's other registered studies.
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cheng-Kung University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Science and Technology, Taiwan
- Responsible party
- Principal investigator, Tzu-Yun Wang, National Cheng-Kung University Hospital
- Investigators
- Tzu-Yun Wang, Principal investigator, National Cheng-Kung University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03229642
- Sponsor's protocol ID
- B-BR-105-094
- Status last verified
- Sep 2020
- First submitted
- 11 Jul 2017
- Last updated
- 16 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 33426970
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03229642
- Acronym / sponsor ID
- B-BR-105-094
- Keywords
- repetitive transcranial magnetic stimulation, opioid use disorder, craving, functional magnetic resonance imaging, neuropsychological tests
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- National Cheng-Kung University HospitalUniversity, hospital or other
- Collaborators
- Ministry of Science and Technology, Taiwan
- Study start
- 1 Aug 2017 (actual)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 25 Jul 2017 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active rTMS treatment | Experimental | Device: Active rTMSThe 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. |
| Sham rTMS treatment | Sham comparator | Device: Sham rTMSThe 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. |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
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 |
|---|---|---|
| Active rTMSThe 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. | Device | Active rTMS treatment |
| Sham rTMSThe 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. | Device | Sham rTMS treatment |
Primary outcome
The treatment retention rate
Time frame: 12 weeks
To compare the treatment retention rate between the active and sham rTMS groups from baseline to endpoint (12 weeks).
The treatment attendance rate
Time frame: 12 weeks
To compare the treatment attendance rate between the active and sham rTMS groups from baseline to endpoint (12 weeks).
Urinary assessment
Time frame: 12 weeks
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.
13 secondary outcomes
fMRI
Time frame: 5 weeks
Immunological markers
Time frame: 12 weeks
Wechsler Memory Scale - third edition(WMS-III)
Time frame: 12 weeks
Wisconsin Card Sorting Test(WCST)
Time frame: 12 weeks
Continuous performance tests(CPT)
Time frame: 12 weeks
Side effect checklist
Time frame: 12 weeks
Assessment of craving
Time frame: 12 weeks
17-item Hamilton Depression Rating Scale (HDRS)
Time frame: 12 weeks
World Health Organization's Quality of Life Assessment-Brief of Taiwan (WHOQOL-BREF TW)
Time frame: 12 weeks
Family APGAR index
Time frame: 12 weeks
The Opiate Treatment Index (OTI)
Time frame: 12 weeks
Clinical Global Impressions (CGI)
Time frame: 12 weeks
Barratt Impulsiveness Scale(BIS)
Time frame: 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2020.
- Derived from this study: PubMed 33426970Tsai 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.
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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. This study is not recruiting at the moment.
Tzu-Yun Wang principal investigator
National Cheng-Kung University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active rTMS in people with Transcranial Magnetic Stimulation and Heroin Dependence, run by National Cheng-Kung University Hospital at 1 site in Taiwan.
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 4 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 16 Sep 2020. 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 Taiwan. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Tzu-Yun Wang (+886-6-2353535 ext. 5940, tzuyun0105@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The treatment retention rate (time frame: 12 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03229642, which also lists 1 linked publication.
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 16 Sep 2020.