Transcranial Magnetic Stimulation in the Treatment of Addiction (MAGENTA)

Repetitive Transcranial Magnetic Stimulation (rTMS) in Alcohol Dependent Patients: a Mechanistic Study.

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.

Study Overview

• Status: Unknown
• Conditions: Alcohol Addiction
• Intervention / Treatment: Other: Verum rTMS; Other: Sham rTMS

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Maarten Belgers, MD; Phone Number: +31-88-606- 1600; Email: m.belgers@iriszorg.nl
• Study Contact Backup: Name: Ant Schellekens, MD, PhD

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands
      • IrisZorg
      • Principal Investigator: Maarten Belgers, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 23 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Verum rTMS; 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.	Other: Verum rTMS; 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.
Sham Comparator: Sham TMS; 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.	Other: Sham rTMS; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	8 weeks after start of treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	2 weeks after start of treatment
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).	4 weeks after start of treatment
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).	12 weeks after start of treatment
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).	2 weeks after start of treatment
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).	4 weeks after start of treatment
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).	8 weeks after start of treatment
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).	12 weeks after start of treatment
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.	at 2 weeks after start treatement
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.	at 4 weeks after start treatement
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.	at 8 weeks after start treatement
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.	at 12 weeks after start treatement
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.	at 2 weeks after start treatement
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.	at 4 weeks after start treatement
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.	at 8 weeks after start treatement
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.	at 12 weeks after start treatement
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.	at 2 weeks after start treatement
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.	at 4 weeks after start treatement
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.	at 8 weeks after start treatement
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.	at 12 weeks after start treatement
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).	at 2 weeks after start treatment
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).	at 4 weeks after start treatment
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).	at 8 weeks after start treatment
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).	at 12 weeks after start treatment
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.	at 2 weeks after start treatment
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.	at 4 weeks after start treatment
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.	at 8 weeks after start treatment

Collaborators and Investigators

• Sponsor: IrisZorg
• Investigators: Principal Investigator: Maarten Belgers, MD, IrisZorg

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Helpful Links

• site of addiction care organisation and sponsor
• site of university hospital where treatment takes place

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Anticipated): April 1, 2015
• Study Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: October 22, 2013
• First Submitted That Met QC Criteria: October 25, 2013
• First Posted (Estimate): October 31, 2013

Study Record Updates

• Last Update Posted (Estimate): October 31, 2013
• Last Update Submitted That Met QC Criteria: October 25, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: craving; addiction; alcohol; EEG; rTMS; TMS; use; LPP; p300; ERN; SST; CCT; AAAT
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Compulsive Behavior; Impulsive Behavior; Alcoholism; Behavior, Addictive
• Other Study ID Numbers: NISPA-IZ/MB22