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Transcranial Magnetic Stimulation in the Treatment of Addiction (MAGENTA)

Primary Purpose

Alcohol Addiction

Status
Unknown status
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
Verum rTMS
Sham rTMS
Sponsored by
IrisZorg
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alcohol Addiction focused on measuring alcohol, addiction, TMS, craving, use, rTMS, EEG, LPP, p300, ERN, SST, CCT, AAAT

Eligibility Criteria

23 Years - 65 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Right-handed males between 23-65 years of age
  • A primary diagnose of alcohol dependence (meeting the DSM-IV-TR criteria 303.90/ICD-10 F10.2)
  • Written consent for participation of the study.

Exclusion Criteria:

  • MATE outcome <4 (as extracted from part 4 MATE at enrollment phase)MATE= Dutch screening instrument on (among others) addiction severity
  • Presence of a current or past relevant somatic or neurological disorder
  • Meeting the DSM-IV-TR criteria for a current bipolar disorder, schizophrenia, anxiety disorder or moderate to severe depressive disorder. These disorders would be a possible great confounder. Measured with the MINI-plus.
  • Meeting the DSM-IV-TR criteria for current (in the past 2 weeks) dependence of substances other than alcohol, nicotine or caffeine. Information present in MATE.
  • Participant-bound factors that may endanger participants or may jeopardize study adherence, because of failure to understand and/or comply with instructions (e.g. current, disruptive symptoms such as psychotic symptoms or severe cognitive impairment)
  • Contra-indications resulting from the use of rTMS:

    • Epilepsy, convulsion or seizure
    • Serious head trauma or brain surgery
    • Large or ferromagnetic metal parts in the head (except for a dental wire)
    • Implanted cardiac pacemaker or neurostimulator

Sites / Locations

  • IrisZorg

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Verum rTMS

Sham TMS

Arm Description

n=15. After detoxification of alcohol (maximum 4 days) rTMS treatment will start : 20 sessions (5 times during 4 weeks)of verum rTMS on the right dorsolateral prefrontal cortex. Measurements of all objectives at baseline and 2,4,8 and 12 weeks after start treatment.

n=15. After detoxification of alcohol (maximum 4 days) rTMS treatment will start : 20 sessions (5 times during 4 weeks)of sham rTMS on the right dorsolateral prefrontal cortex. Measurements of all objectives at basleine and 2,4,8 and 12 weeks after start treatment.

Outcomes

Primary Outcome Measures

The change from baseline on the amplitude of the LPP at 8 weeks
To investigate the effect of 20 sessions of rTMS on the change in amplitude of the Late Positive Potentials (LPP) (P300 and Slow Potential (SP)) as measured with EEG at 8 weeks after start of treatment (baseline measurement).

Secondary Outcome Measures

The change from baseline on the amplitude of the LPP at 2 weeks
To investigate the effect of 20 sessions of rTMS on the change in amplitude of the Late Positive Potentials (LPP) (P300 and Slow Potential (SP)) as measured with EEG at 2 weeks after start of treatment (baseline measurement).
The change from baseline on the amplitude of the LPP at 4 weeks
To investigate the effect of 20 sessions of rTMS on the change in amplitude of the Late Positive Potentials (LPP) (P300 and Slow Potential (SP)) as measured with EEG at 4 weeks after start of treatment (baseline measurement).
The change from baseline on the amplitude of the LPP at 12 weeks
To investigate the effect of 20 sessions of rTMS on the change in amplitude of the Late Positive Potentials (LPP) (P300 and Slow Potential (SP)) as measured with EEG at 12 weeks after start of treatment (baseline measurement).
The change from baseline on the amplitude of the ERN at 2 weeks
To investigate the effect of 20 sessions of rTMS on the change in amplitude of the Error Related Negativity (ERN) as measured with EEG at 2 weeks after start of treatment (baseline measurement).
The change from baseline on the amplitude of the ERN at 4 weeks
To investigate the effect of 20 sessions of rTMS on the change in amplitude of the Error Related Negativity (ERN) as measured with EEG at 4 weeks after start of treatment (baseline measurement).
The change from baseline on the amplitude of the ERN at 8 weeks
To investigate the effect of 20 sessions of rTMS on the change in amplitude of the Error Related Negativity (ERN) as measured with EEG at 8 weeks after start of treatment (baseline measurement).
The change from baseline on the amplitude of the ERN at 12 weeks
To investigate the effect of 20 sessions of rTMS on the change in amplitude of the Error Related Negativity (ERN) as measured with EEG at 12 weeks after start of treatment (baseline measurement).
Change from baseline on SST at 2 weeks
To investigate the effect of 20 sessions of rTMS on the change in cognitive performance at 2 weeks follow-up, by conducting a Stop-Signal Task (SST)per computer.
Change from baseline on SST at 4 weeks
To investigate the effect of 20 sessions of rTMS on the change in cognitive performance at 4 weeks follow-up, by conducting a Stop-Signal Task (SST)per computer.
Change from baseline on SST at 8 weeks
To investigate the effect of 20 sessions of rTMS on the change in cognitive performance at 12 weeks follow-up, by conducting a Stop-Signal Task (SST) per computer.
Change from baseline on SST at 12 weeks
To investigate the effect of 20 sessions of rTMS on the change in cognitive performance at 12 weeks follow-up, by conducting a Stop-Signal Task (SST) per computer.
Change from baseline on CCT at 2 weeks
To investigate the effect of 20 sessions of rTMS on the change in cognitive performance at 2 weeks follow-up, by conducting a Columbia Card Task (CCT) per computer.
Change from baseline on CCT at 4 weeks
To investigate the effect of 20 sessions of rTMS on the change in cognitive performance at 4 weeks follow-up, by conducting a Columbia Card Task (CCT) per computer.
Change from baseline on CCT at 8 weeks
To investigate the effect of 20 sessions of rTMS on the change in cognitive performance at 8 weeks follow-up, by conducting a Columbia Card Task (CCT) per computer.
Change from baseline on CCT at 12 weeks
To investigate the effect of 20 sessions of rTMS on the change in cognitive performance at 12 weeks follow-up, by conducting a Columbia Card Task (CCT) per computer.
Change from baseline on AAAT at 2 weeks
To investigate the effect of 20 sessions of rTMS on the change in cognitive performance at 2 weeks follow-up, by conducting a Alcohol Approach Avoidance Task (AAAT) per computer.
Change from baseline on AAAT at 4 weeks
To investigate the effect of 20 sessions of rTMS on the change in cognitive performance at 4 weeks follow-up, by conducting a Alcohol Approach Avoidance Task (AAAT) per computer.
Change from baseline on AAAT at 8 weeks
To investigate the effect of 20 sessions of rTMS on the change in cognitive performance at 8 weeks follow-up, by conducting a Alcohol Approach Avoidance Task (AAAT) per computer.
Change from baseline on AAAT at 12 weeks
To investigate the effect of 20 sessions of rTMS on the change in cognitive performance at 12 weeks follow-up, by conducting a Alcohol Approach Avoidance Task (AAAT) per computer.
Change form baseline on craving at 2 weeks after start treatment
To investigate the change of 20 sessions of rTMS in perceived patient reported craving at 2 weeks after start treatment as measured with the Obsessive Compulsing Drinking Scale (OCDS), Alcohol Urge Questionnaire (AUQ) and a craving Visual Analogue Scale (VAS).
Change form baseline on craving at 4 weeks after start treatment
To investigate the change of 20 sessions of rTMS in perceived patient reported craving at 4 weeks after start treatment as measured with the Obsessive Compulsing Drinking Scale (OCDS), Alcohol Urge Questionnaire (AUQ) and a craving Visual Analogue Scale (VAS).
Change form baseline on craving at 8 weeks after start treatment
To investigate the change of 20 sessions of rTMS in perceived patient reported craving at 8 weeks after start treatment as measured with the Obsessive Compulsing Drinking Scale (OCDS), Alcohol Urge Questionnaire (AUQ) and a craving Visual Analogue Scale (VAS).
Change form baseline on craving at 12 weeks after start treatment
To investigate the change of 20 sessions of rTMS in perceived patient reported craving at 12 weeks after start treatment as measured with the Obsessive Compulsing Drinking Scale (OCDS), Alcohol Urge Questionnaire (AUQ) and a craving Visual Analogue Scale (VAS).
Change form baseline on alcohol use at 2 weeks after start treatment
To investigate the effect of 20 sessions of rTMS on the change in alcohol use 2 weeks from baseline by filling in a dairy on treatment days 5 times a week.
Change form baseline on alcohol use at 4 weeks after start treatment
To investigate the effect of 20 sessions of rTMS on the change in alcohol use 4 weeks from baseline by filling in a dairy on treatment days 5 times a week.
Change form baseline on alcohol use at 12 weeks after start treatment
To investigate the effect of 20 sessions of rTMS on the change in alcohol use 12 weeks from baseline by using the Alcohol Timeline Follow Back (TLFB) method.

Full Information

First Posted
October 22, 2013
Last Updated
October 25, 2013
Sponsor
IrisZorg
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1. Study Identification

Unique Protocol Identification Number
NCT01973127
Brief Title
Transcranial Magnetic Stimulation in the Treatment of Addiction
Acronym
MAGENTA
Official Title
Repetitive Transcranial Magnetic Stimulation (rTMS) in Alcohol Dependent Patients: a Mechanistic Study.
Study Type
Interventional

2. Study Status

Record Verification Date
October 2013
Overall Recruitment Status
Unknown status
Study Start Date
May 2014 (undefined)
Primary Completion Date
April 2015 (Anticipated)
Study Completion Date
December 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
IrisZorg

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The investigators hypothesize that repetitive transcranial magnetic stimulation (rTMS) on the right side of the head will make craving towards alcohol less severe in recently detoxified alcohol addicted patients. Although there are successful treatment option to detoxify patients form their alcohol use, many patients tend to relapse. This relapse is mainly caused by a high level of (uncontrollable) craving towards alcohol. This aspect of addiction is with the existing options hard to treat, there is a great need of new successful treatment modalities. rTMS is a FDA approved treatment method for depression. Recently some small scale studies have shown promising results on rTMS in the treatment of addiction. In this study the investigators focus on alcohol addiction since it is the addiction with the highest morbidity and mortality in the Netherlands.
Detailed Description
In this study the investigators focus on three levels of interest: the biological level, the functional level and the clinical level. The investigators will measure the effect of rTMS directly on brain activity through EEG recording. The investigators investigate its effects on cognitive performance through the use of neuropsychological computer tasks. The investigators will address clinical behavior (craving and alcohol use) with questionnaires.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcohol Addiction
Keywords
alcohol, addiction, TMS, craving, use, rTMS, EEG, LPP, p300, ERN, SST, CCT, AAAT

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Verum rTMS
Arm Type
Experimental
Arm Description
n=15. After detoxification of alcohol (maximum 4 days) rTMS treatment will start : 20 sessions (5 times during 4 weeks)of verum rTMS on the right dorsolateral prefrontal cortex. Measurements of all objectives at baseline and 2,4,8 and 12 weeks after start treatment.
Arm Title
Sham TMS
Arm Type
Sham Comparator
Arm Description
n=15. After detoxification of alcohol (maximum 4 days) rTMS treatment will start : 20 sessions (5 times during 4 weeks)of sham rTMS on the right dorsolateral prefrontal cortex. Measurements of all objectives at basleine and 2,4,8 and 12 weeks after start treatment.
Intervention Type
Other
Intervention Name(s)
Verum rTMS
Intervention Description
rTMS on the right dorsolateral prefrontal cortex. TMS procedure: The resting motor threshold (RMT) will be defined in each subject as the minimal stimulation intensity evoking an MEP of ≥ 0.05 mV in 50% of the trials in the muscle of the right thumb (M. abductor pollicis brevis). TMS will be conducted in the form of 'conventional rTMS', whereby 30 trains of 10 Hz pulses with a duration of 5 seconds and an inter-train interval of 25 seconds are applied to the righ dorsolateral prefrontal cortex (50 pulses per train, 6000 pulses per session). Used equipment: Magstim Rapid 2 device.
Intervention Type
Other
Intervention Name(s)
Sham rTMS
Intervention Description
TMS procedure: The resting motor threshold (RMT) will be defined in each subject as the minimal stimulation intensity evoking an MEP of ≥ 0.05 mV in 50% of the trials in the muscle of the right thumb (M. abductor pollicis brevis). Like in verum TMS coil will be placed on the skull, but no magnetic field will be pulsed. Used equipment: Magstim Rapid 2 device.
Primary Outcome Measure Information:
Title
The change from baseline on the amplitude of the LPP at 8 weeks
Description
To investigate the effect of 20 sessions of rTMS on the change in amplitude of the Late Positive Potentials (LPP) (P300 and Slow Potential (SP)) as measured with EEG at 8 weeks after start of treatment (baseline measurement).
Time Frame
8 weeks after start of treatment.
Secondary Outcome Measure Information:
Title
The change from baseline on the amplitude of the LPP at 2 weeks
Description
To investigate the effect of 20 sessions of rTMS on the change in amplitude of the Late Positive Potentials (LPP) (P300 and Slow Potential (SP)) as measured with EEG at 2 weeks after start of treatment (baseline measurement).
Time Frame
2 weeks after start of treatment
Title
The change from baseline on the amplitude of the LPP at 4 weeks
Description
To investigate the effect of 20 sessions of rTMS on the change in amplitude of the Late Positive Potentials (LPP) (P300 and Slow Potential (SP)) as measured with EEG at 4 weeks after start of treatment (baseline measurement).
Time Frame
4 weeks after start of treatment
Title
The change from baseline on the amplitude of the LPP at 12 weeks
Description
To investigate the effect of 20 sessions of rTMS on the change in amplitude of the Late Positive Potentials (LPP) (P300 and Slow Potential (SP)) as measured with EEG at 12 weeks after start of treatment (baseline measurement).
Time Frame
12 weeks after start of treatment
Title
The change from baseline on the amplitude of the ERN at 2 weeks
Description
To investigate the effect of 20 sessions of rTMS on the change in amplitude of the Error Related Negativity (ERN) as measured with EEG at 2 weeks after start of treatment (baseline measurement).
Time Frame
2 weeks after start of treatment
Title
The change from baseline on the amplitude of the ERN at 4 weeks
Description
To investigate the effect of 20 sessions of rTMS on the change in amplitude of the Error Related Negativity (ERN) as measured with EEG at 4 weeks after start of treatment (baseline measurement).
Time Frame
4 weeks after start of treatment
Title
The change from baseline on the amplitude of the ERN at 8 weeks
Description
To investigate the effect of 20 sessions of rTMS on the change in amplitude of the Error Related Negativity (ERN) as measured with EEG at 8 weeks after start of treatment (baseline measurement).
Time Frame
8 weeks after start of treatment
Title
The change from baseline on the amplitude of the ERN at 12 weeks
Description
To investigate the effect of 20 sessions of rTMS on the change in amplitude of the Error Related Negativity (ERN) as measured with EEG at 12 weeks after start of treatment (baseline measurement).
Time Frame
12 weeks after start of treatment
Title
Change from baseline on SST at 2 weeks
Description
To investigate the effect of 20 sessions of rTMS on the change in cognitive performance at 2 weeks follow-up, by conducting a Stop-Signal Task (SST)per computer.
Time Frame
at 2 weeks after start treatement
Title
Change from baseline on SST at 4 weeks
Description
To investigate the effect of 20 sessions of rTMS on the change in cognitive performance at 4 weeks follow-up, by conducting a Stop-Signal Task (SST)per computer.
Time Frame
at 4 weeks after start treatement
Title
Change from baseline on SST at 8 weeks
Description
To investigate the effect of 20 sessions of rTMS on the change in cognitive performance at 12 weeks follow-up, by conducting a Stop-Signal Task (SST) per computer.
Time Frame
at 8 weeks after start treatement
Title
Change from baseline on SST at 12 weeks
Description
To investigate the effect of 20 sessions of rTMS on the change in cognitive performance at 12 weeks follow-up, by conducting a Stop-Signal Task (SST) per computer.
Time Frame
at 12 weeks after start treatement
Title
Change from baseline on CCT at 2 weeks
Description
To investigate the effect of 20 sessions of rTMS on the change in cognitive performance at 2 weeks follow-up, by conducting a Columbia Card Task (CCT) per computer.
Time Frame
at 2 weeks after start treatement
Title
Change from baseline on CCT at 4 weeks
Description
To investigate the effect of 20 sessions of rTMS on the change in cognitive performance at 4 weeks follow-up, by conducting a Columbia Card Task (CCT) per computer.
Time Frame
at 4 weeks after start treatement
Title
Change from baseline on CCT at 8 weeks
Description
To investigate the effect of 20 sessions of rTMS on the change in cognitive performance at 8 weeks follow-up, by conducting a Columbia Card Task (CCT) per computer.
Time Frame
at 8 weeks after start treatement
Title
Change from baseline on CCT at 12 weeks
Description
To investigate the effect of 20 sessions of rTMS on the change in cognitive performance at 12 weeks follow-up, by conducting a Columbia Card Task (CCT) per computer.
Time Frame
at 12 weeks after start treatement
Title
Change from baseline on AAAT at 2 weeks
Description
To investigate the effect of 20 sessions of rTMS on the change in cognitive performance at 2 weeks follow-up, by conducting a Alcohol Approach Avoidance Task (AAAT) per computer.
Time Frame
at 2 weeks after start treatement
Title
Change from baseline on AAAT at 4 weeks
Description
To investigate the effect of 20 sessions of rTMS on the change in cognitive performance at 4 weeks follow-up, by conducting a Alcohol Approach Avoidance Task (AAAT) per computer.
Time Frame
at 4 weeks after start treatement
Title
Change from baseline on AAAT at 8 weeks
Description
To investigate the effect of 20 sessions of rTMS on the change in cognitive performance at 8 weeks follow-up, by conducting a Alcohol Approach Avoidance Task (AAAT) per computer.
Time Frame
at 8 weeks after start treatement
Title
Change from baseline on AAAT at 12 weeks
Description
To investigate the effect of 20 sessions of rTMS on the change in cognitive performance at 12 weeks follow-up, by conducting a Alcohol Approach Avoidance Task (AAAT) per computer.
Time Frame
at 12 weeks after start treatement
Title
Change form baseline on craving at 2 weeks after start treatment
Description
To investigate the change of 20 sessions of rTMS in perceived patient reported craving at 2 weeks after start treatment as measured with the Obsessive Compulsing Drinking Scale (OCDS), Alcohol Urge Questionnaire (AUQ) and a craving Visual Analogue Scale (VAS).
Time Frame
at 2 weeks after start treatment
Title
Change form baseline on craving at 4 weeks after start treatment
Description
To investigate the change of 20 sessions of rTMS in perceived patient reported craving at 4 weeks after start treatment as measured with the Obsessive Compulsing Drinking Scale (OCDS), Alcohol Urge Questionnaire (AUQ) and a craving Visual Analogue Scale (VAS).
Time Frame
at 4 weeks after start treatment
Title
Change form baseline on craving at 8 weeks after start treatment
Description
To investigate the change of 20 sessions of rTMS in perceived patient reported craving at 8 weeks after start treatment as measured with the Obsessive Compulsing Drinking Scale (OCDS), Alcohol Urge Questionnaire (AUQ) and a craving Visual Analogue Scale (VAS).
Time Frame
at 8 weeks after start treatment
Title
Change form baseline on craving at 12 weeks after start treatment
Description
To investigate the change of 20 sessions of rTMS in perceived patient reported craving at 12 weeks after start treatment as measured with the Obsessive Compulsing Drinking Scale (OCDS), Alcohol Urge Questionnaire (AUQ) and a craving Visual Analogue Scale (VAS).
Time Frame
at 12 weeks after start treatment
Title
Change form baseline on alcohol use at 2 weeks after start treatment
Description
To investigate the effect of 20 sessions of rTMS on the change in alcohol use 2 weeks from baseline by filling in a dairy on treatment days 5 times a week.
Time Frame
at 2 weeks after start treatment
Title
Change form baseline on alcohol use at 4 weeks after start treatment
Description
To investigate the effect of 20 sessions of rTMS on the change in alcohol use 4 weeks from baseline by filling in a dairy on treatment days 5 times a week.
Time Frame
at 4 weeks after start treatment
Title
Change form baseline on alcohol use at 12 weeks after start treatment
Description
To investigate the effect of 20 sessions of rTMS on the change in alcohol use 12 weeks from baseline by using the Alcohol Timeline Follow Back (TLFB) method.
Time Frame
at 8 weeks after start treatment

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
23 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Right-handed males between 23-65 years of age A primary diagnose of alcohol dependence (meeting the DSM-IV-TR criteria 303.90/ICD-10 F10.2) Written consent for participation of the study. Exclusion Criteria: MATE outcome <4 (as extracted from part 4 MATE at enrollment phase)MATE= Dutch screening instrument on (among others) addiction severity Presence of a current or past relevant somatic or neurological disorder Meeting the DSM-IV-TR criteria for a current bipolar disorder, schizophrenia, anxiety disorder or moderate to severe depressive disorder. These disorders would be a possible great confounder. Measured with the MINI-plus. Meeting the DSM-IV-TR criteria for current (in the past 2 weeks) dependence of substances other than alcohol, nicotine or caffeine. Information present in MATE. Participant-bound factors that may endanger participants or may jeopardize study adherence, because of failure to understand and/or comply with instructions (e.g. current, disruptive symptoms such as psychotic symptoms or severe cognitive impairment) Contra-indications resulting from the use of rTMS: Epilepsy, convulsion or seizure Serious head trauma or brain surgery Large or ferromagnetic metal parts in the head (except for a dental wire) Implanted cardiac pacemaker or neurostimulator
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Maarten Belgers, MD
Phone
+31-88-606- 1600
Email
m.belgers@iriszorg.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Ant Schellekens, MD, PhD
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maarten Belgers, MD
Organizational Affiliation
IrisZorg
Official's Role
Principal Investigator
Facility Information:
Facility Name
IrisZorg
City
Nijmegen
State/Province
Gelderland
Country
Netherlands
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maarten Belgers, MD

12. IPD Sharing Statement

Citations:
PubMed Identifier
19914283
Citation
Feil J, Zangen A. Brain stimulation in the study and treatment of addiction. Neurosci Biobehav Rev. 2010 Mar;34(4):559-74. doi: 10.1016/j.neubiorev.2009.11.006. Epub 2009 Nov 13.
Results Reference
background
PubMed Identifier
22200135
Citation
Barr MS, Farzan F, Wing VC, George TP, Fitzgerald PB, Daskalakis ZJ. Repetitive transcranial magnetic stimulation and drug addiction. Int Rev Psychiatry. 2011 Oct;23(5):454-66. doi: 10.3109/09540261.2011.618827.
Results Reference
background
PubMed Identifier
19183128
Citation
Amiaz R, Levy D, Vainiger D, Grunhaus L, Zangen A. Repeated high-frequency transcranial magnetic stimulation over the dorsolateral prefrontal cortex reduces cigarette craving and consumption. Addiction. 2009 Apr;104(4):653-60. doi: 10.1111/j.1360-0443.2008.02448.x. Epub 2009 Jan 12.
Results Reference
background
Links:
URL
http://www.iriszorg.nl
Description
site of addiction care organisation and sponsor
URL
http://www.umcn.nl
Description
site of university hospital where treatment takes place
URL
http://www.nispa.nl
Description
scientific institute related to the study

Learn more about this trial

Transcranial Magnetic Stimulation in the Treatment of Addiction

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