New Therapeutic Strategies for Inhibitory Control in Alcoholism

New Therapeutic Strategies for Inhibitory Control Improvement of Alcohol-dependent Patients

This experimental research studies the efficacy of two different treatments for inhibitory control improvement in alcohol-dependent individuals, one consisting of Retrieval-Extinction Learning ( alcohol AAT Task) and the other consisting in rTMS of the right dorsolateral prefrontal cortex.

Study Overview

• Status: Unknown
• Conditions: Alcoholism
• Intervention / Treatment: Behavioral: Retrieval-Extinction Learning; Other: rTMS; Other: SAM

Detailed Description

The main purpose of this study is to demonstrate the efficacy of two different treatments for inhibitory control improvement (measured by the modified Stop signal task): a behavioral treatment based on Retrieval-Extinction Learning, through the AAT (Alcohol Approach Avoiding Task) and a treatment based on the neuromodulation of prefrontal cortex through the rTMS (repetitive transcraneal magnetic stimulation) technique. To carry out this study, 105 alcoholic patients will be compared for clinical variables (abstinence/relapses), self-informed (UPPS) and behvavioral impulsivity (Stop signal task), along with biological measures for polymorphism determinations. Alcohol-dependent individuals will be divided into 4 groups of study (1:1 proportion for Retrieval-Extinction Learning with AAT and 2:1 (double for the effective technique comparing to placebo/control) for rTMS): Group 1 (N=30): exposure to an alcohol-related video followed by AAT; Group 2 (N=30): neutral-content video followed by AAT; Group 4 (30): active stimulation rTMS (10 Hz) ; Group 4 (N=15): placebo stimulation SAM.

• Study Type: Interventional
• Enrollment (Anticipated): 105
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women aged between 18 and 50 years old.
• A minimum of 28 days of abstinence
• Consent to participate in the study.

Exclusion Criteria:

• Subjects with other substance dependence ( with the exception of tobacco)
• Subjects with a history of brain injury or neurological diseases
• Denial for study participation
• Non-spanish speakers
• rTMS selected participants with be assed in order to discard epilepsy, presence for metallic elements and CNS valves

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exposure; Exposure to a 5 minutes video related to alcohol consumption (updating/retrieval), followed by 10 minutes of the alcohol- AAT(Approach Avoidance Task) (extinction), during 4 days of training (2 weeks).	Behavioral: Retrieval-Extinction Learning; The intervention consists of the accomplishment of the task of approach-avoidance of alcohol during 4 days of training. Subjects are instructed to respond with an approach movement (pulling a lever) to neutral images and to respond with avoidance movement (pushing the lever) to images of alcohol.
Active Comparator: No exposure; Exposure to a 5 minutes video with neutral content (no retrieval) followed by 10 minutes of the alcohol- AAT (Approach Avoidance Task) , during 4 days of training.	Behavioral: Retrieval-Extinction Learning; The intervention consists of the accomplishment of the task of approach-avoidance of alcohol during 4 days of training. Subjects are instructed to respond with an approach movement (pulling a lever) to neutral images and to respond with avoidance movement (pushing the lever) to images of alcohol.
Experimental: Active rTMS; Each session (5 sessions along 2 weeks), patients receive active stimulation with repetitive transcraneal magnetic stimulation (rTMS) of the right dorsolateral prefrontal cortex.	Other: rTMS; Previous to rTMS completion, MRI scans were performed in order to determinate the motor threshold trough 1Hz stimuli and locate the desired area with the neuronavigator. Motor threshold is defined as the stimulus with less intensity, able to generate a motor potential of at least 50 µV in 10 trials. Next, patients were called for 5 times per week, along 2 weeks, for receiving brain stimulation with Magstim Rapid coil. rTMS is performed at 10 Hz, during 4.9 seconds,for each set of stimuli (20), with a interval between sets of 30 seconds.
Sham Comparator: SAM; Pacients receiving a sham stimulation (SAM), with a similar procedure to the experimental condition	Other: SAM; Previous to rTMS completion, MRI scans were performed in order to determinate the motor threshold trough 1Hz stimuli and locate the desired area with the neuronavigator. Motor threshold is defined as the stimulus with less intensity, able to generate a motor potential of at least 50 µV in 10 trials. Next, patients were called for 5 times per week, along 2 weeks, for receiving brain stimulation with SAM coil.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapses	Number of relapses	3 months
Heavy drinking	Number of days of heavy drinking	3 months
Abstinence	Days of accumulated abstinence	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Behavioral Impulsivity	Stop signal task reaction times	2 days
Self-reported Impulsivity	scores for UPPS	2 days
Polymorphism distribution of CRH and ANK3 genes	Biological determinations-lymphocyte samples	2 days

Collaborators and Investigators

• Sponsor: Hospital Universitario 12 de Octubre
• Collaborators: Ministerio de Sanidad, Servicios Sociales e Igualdad

Publications and helpful links

General Publications

• Wiers RW, Eberl C, Rinck M, Becker ES, Lindenmeyer J. Retraining automatic action tendencies changes alcoholic patients' approach bias for alcohol and improves treatment outcome. Psychol Sci. 2011 Apr;22(4):490-7. doi: 10.1177/0956797611400615. Epub 2011 Mar 9.
• Mishra BR, Nizamie SH, Das B, Praharaj SK. Efficacy of repetitive transcranial magnetic stimulation in alcohol dependence: a sham-controlled study. Addiction. 2010 Jan;105(1):49-55. doi: 10.1111/j.1360-0443.2009.02777.x.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Anticipated): September 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: February 15, 2017
• First Submitted That Met QC Criteria: February 15, 2017
• First Posted (Actual): February 20, 2017

Study Record Updates

• Last Update Posted (Actual): February 21, 2019
• Last Update Submitted That Met QC Criteria: February 20, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: rTMS; AAT; Relapses; Alcohol-Dependence
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism
• Other Study ID Numbers: 2015/099

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No