NCT03229642

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
60

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Aug 2017

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 11, 2017

Completed
14 days until next milestone

First Posted

Study publicly available on registry

July 25, 2017

Completed
7 days until next milestone

Study Start

First participant enrolled

August 1, 2017

Completed
5.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2022

Completed
Last Updated

September 16, 2020

Status Verified

September 1, 2020

Enrollment Period

5.4 years

First QC Date

July 11, 2017

Last Update Submit

September 13, 2020

Conditions

Transcranial Magnetic StimulationHeroin Dependence

Keywords

repetitive transcranial magnetic stimulationopioid use disordercravingfunctional magnetic resonance imagingneuropsychological tests

Outcome Measures

Primary Outcomes (3)

  • The treatment retention rate

    To compare the treatment retention rate between the active and sham rTMS groups from baseline to endpoint (12 weeks).

    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).

    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.

    12 weeks

Secondary Outcomes (13)

  • fMRI

    5 weeks

  • Immunological markers

    12 weeks

  • Wechsler Memory Scale - third edition(WMS-III)

    12 weeks

  • Wisconsin Card Sorting Test(WCST)

    12 weeks

  • Continuous performance tests(CPT)

    12 weeks

  • +8 more secondary outcomes

Study Arms (2)

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.

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.

Device: Sham rTMS

Interventions

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.

Active rTMS treatment
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.

Sham rTMS treatment

Eligibility Criteria

Age20 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Cheng Kung University Hospital

Tainan, Taiwan

RECRUITING

Related Publications (1)

  • 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.

    PMID: 33426970DERIVED

MeSH Terms

Conditions

Heroin DependenceOpioid-Related Disorders

Condition Hierarchy (Ancestors)

Narcotic-Related DisordersSubstance-Related DisordersChemically-Induced DisordersMental Disorders

Study Officials

  • Tzu-Yun Wang

    National Cheng-Kung University Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Tzu-Yun Wang

CONTACT

+886-6-2353535tzuyun0105@hotmail.com

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Doctor

Study Record Dates

First Submitted

July 11, 2017

First Posted

July 25, 2017

Study Start

August 1, 2017

Primary Completion

December 31, 2022

Study Completion

December 31, 2022

Last Updated

September 16, 2020

Record last verified: 2020-09

Locations

TW(1)