xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05997212</url>
    </required_header>
    <id_info>
      <org_study_id>101.H</org_study_id>
      <nct_id>NCT05997212</nct_id>
    </id_info>
    <brief_title>Effect of Repetitive TMS on Executive Function in Alcohol Use Disorder</brief_title>
    <official_title>Effect of Repetitive Transcranial Magnetic Stimulation on the Executive Function in Alcohol Use Disorder</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Universidad Nacional Autonoma de Mexico</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Council of Science and Technology, Mexico</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Universidad Nacional Autonoma de Mexico</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        Alcohol Use Disorder (AUD) is a major public health problem that affects the physical,&#xD;
        social, family, and mental integrity of the sufferer. Behavioral self-regulation is&#xD;
        compromised in AUD, and a benefit has been reported with the application of repetitive&#xD;
        transcranial magnetic stimulation and emotional self-regulation. The aim of this study is to&#xD;
        investigate the efficacy of high-frequency rTMS to improve executive functions in patients in&#xD;
        abstinence from AUD.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        It is proposed that people with a greater predisposition to develop AUD have alterations in&#xD;
        executive functions, due to maladaptive cellular homeostatic processes and neuronal circuits&#xD;
        stimulated by substances, and that these alterations persist even after the withdrawal of the&#xD;
        substance (Nestler and Aghajanian, 1997). Also as a multifactorial disorder, it has been&#xD;
        considered the implication of family history of consumption (Khemiri et al., 2020; Peterson&#xD;
        et al., 1990 &amp; Tarter et al., 1989) and individual traits, like poor performance on a&#xD;
        cognitive test compared to controls, (Shnitko et al., 2018 &amp; Goudriaan et al., 2011) as a&#xD;
        predictor to develop heavy alcohol consumption or AUD. The alteration in executive functions&#xD;
        seems to manifest with the perseverance of negative behaviors that prevent new forms of&#xD;
        learning and adaptation to situations, and the decrease in the activation of the executive&#xD;
        control network, which is correlated with the severity of the AUD (Mayhugh et al., 2014). One&#xD;
        executive function that may be related to AUD and treatment success is cognitive flexibility,&#xD;
        whose role is to allow thoughts and behaviors to be appropriately adjusted in response to&#xD;
        environmental cognitive demands (Uddin., 2021). Studies have shown that the persistence and&#xD;
        severity of AUD have been related to impaired cognitive flexibility (Stalnaker et al., 2008),&#xD;
        and it is recovered after prolonged alcohol abstinence (Rourke &amp; Grant, 1999). Therefore,&#xD;
        cognitive flexibility may be a treatment biomarker worth exploring. According to a review by&#xD;
        McLellan et al. (2000), 40 to 60 % of the patients who are treated for AUD relapse before the&#xD;
        first year of follow-up after discharge. At least 60% of those treated for an AUD will&#xD;
        relapse within 6 months of treatment (Durazzo and Meyerhoff, 2017; Kirshenbaum et al., 2009;&#xD;
        Maisto et al., 2006a; Meyerhoff and Durazzo, 2010). It is for this reason that new treatments&#xD;
        are still being sought in addition to standard pharmacological and psychotherapeutic&#xD;
        treatments, where non-invasive neuromodulation techniques such as repetitive transcranial&#xD;
        magnetic stimulation (rTMS) have shown promising results (Diana et al., 2017).&#xD;
  &#xD;
        The Food and Drug Administration (FDA) in 2020 approved the use of rTMS as a therapeutic&#xD;
        option for nicotine use disorder, but not for AUD in which positive changes have been found.&#xD;
        For example, Addolorato et al., (2017) used high frequency (10 Hz) rTMS in areas of the&#xD;
        dorsolateral prefrontal cortex (DLPFC) in humans with AUD and found a reduction in alcohol&#xD;
        consumption and an increase in the number of days of drinking abstinence. It has been found&#xD;
        that rTMS on the left DLPC increased inhibitory control and selective attention, and reduced&#xD;
        depressive and somatization features, in subjects with active alcohol consumption (Del Felice&#xD;
        et al., 2016). Since DLPFC is an important region of the executive control network, rTMS in&#xD;
        this region in patients with AUD could induce an increase in functional connectivity of this&#xD;
        network and consequently increase cognitive flexibility. About the effects of rTMS on&#xD;
        cognitive functions, it was found to increase inhibitory control and selective attention (Del&#xD;
        Felice et al., 2016, Diana et al., 2017). For all the above, we proposed to conduct a&#xD;
        longitudinal study that will assess the cognitive and behavioral characteristics of people&#xD;
        with a history of AUD that could play in the first place a crucial part to have developed the&#xD;
        disorder. And the effects of TMS on this population, using the non-invasive technique of MRI&#xD;
        and the neuropsychological tool to assess the cognitive and behavioral effects.&#xD;
  &#xD;
        The aim of this study is to investigate the short- and long-term clinical and cognitive&#xD;
        effects of repetitive transcranial magnetic stimulation (rTMS) at a frequency of 10 Hz on the&#xD;
        left dorsolateral prefrontal cortex in patients with alcohol use disorder in abstinence and&#xD;
        to examine possible changes in brain structure and functional connectivity associated with&#xD;
        this intervention. To do this, the investigators will recruit alcohol-dependent patients and&#xD;
        stimulate them by rTMS twice daily for 4 weeks. The investigators will follow the patients to&#xD;
        determine clinical outcomes at 6 months. The investigators will also measure clinical,&#xD;
        cognitive, structural, and functional brain connectivity to assess short- and long-term&#xD;
        intervention-related changes (measurements at baseline, 4 weeks, and 6 months).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">November 1, 2026</completion_date>
    <primary_completion_date type="Anticipated">May 1, 2025</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>Single-blind randomize clincial trial with parallel groups</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Single (Participant)</masking>
      <masking_description>Single blind. The participants will be the only ones blinded. The rTMS coil will be put backwards in the Sham group.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Change in Wisconsin Card Sorting Task</measure>
      <time_frame>Baseline, 4 weeks, 6 months</time_frame>
      <description>Measured by Wisconsin Card Sorting Task (WCST) to evaluate cognitive flexibility</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change STROOP effect</measure>
      <time_frame>Baseline, 4 weeks, 6 months</time_frame>
      <description>Measured by STROOP test to evaluate control inhibition</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change Visoespatial Memory</measure>
      <time_frame>Baseline, 4 weeks, 6 months</time_frame>
      <description>Measured by Visoespatial Memory test to evaluate visoespatial memory</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change in Taskswitching Task Switch cost</measure>
      <time_frame>Baseline, 4 weeks</time_frame>
      <description>Measured by Taskswitching task to evaluate cognitive flexibility</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Flanker Task Flanker Efect</measure>
      <time_frame>Baseline, 4 weeks</time_frame>
      <description>Measured by Flanker task to evaluate control inhibition</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Nback Task accuracy</measure>
      <time_frame>Baseline, 4 weeks</time_frame>
      <description>Measured by Nback task to evaluate working memory</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Alcohol Craving (VAS)</measure>
      <time_frame>Baseline, 4 weeks, 6 months</time_frame>
      <description>The craving will be measured using a 100 mm visual analogue scales</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in psychopathological symptoms</measure>
      <time_frame>Baseline, 4 weeks, 6 months</time_frame>
      <description>Measured by the Symptoms Questionnaire 90 (SCL-90)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in WHODAS score</measure>
      <time_frame>Baseline, 4 weeks, 6 months</time_frame>
      <description>Measured by Disability Assessment Schedule (WHODAS)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in Anxiety</measure>
      <time_frame>Baseline, 4 weeks, 6 months</time_frame>
      <description>Measured by Hamilton Anxiety Rating Scale (HARS)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in Depression</measure>
      <time_frame>Baseline, 4 weeks, 6 months</time_frame>
      <description>Measured by Hamilton Depression Rating Scale (HDRS)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Changes in functional connectivity</measure>
      <time_frame>Baseline, 4 weeks</time_frame>
      <description>Functional connectivity of the dorsolateral prefrontal with the anterior cingulate cortex, measured with fMRI defined by the temporal correlation in the blood-oxygen-level-dependent signals of the regions. Higher correlations indicate stronger functional connectivity.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">44</enrollment>
    <condition>Alcohol Use Disorder</condition>
    <arm_group>
      <arm_group_label>Active rTMS frequency at 10 Hz</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The intervention will be Repetitive Transcranial Magnetic Stimulation. Each patient will receive treatment stimulation in the left dorsolateral prefrontal cortex (lDLPFC) with a frequency of 10 Hz, that includes 2 sessions per day for 20 consecutive business days for 4 weeks. Each session will consist of the application of rTMS at a frequency of 10 Hz, to 100% of the motor threshold. The lDLPFC target will be determined using their resting state functional connectivity between anterior cingulate cortex and lDLPFC. Our algorithm performs a calculation of the individual localization of the participant's lDLPFC, which will be used for the whole study in that particular participant.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Sham rTMS frequency at 10 Hz</arm_group_label>
      <arm_group_type>Sham Comparator</arm_group_type>
      <description>The intervention will be Repetitive Transcranial Magnetic Stimulation (Sham). For this patients the coil will be located backwards to the skull. Each patient will receive sham stimulation in the left dorsolateral prefrontal cortex (lDLPFC) with a frequency of 10 Hz, that includes 2 sessions per day for 20 consecutive business days for 4 weeks. Each session will consist of the application of rTMS at a frequency of 10 Hz, to 100% of the motor threshold. The lDLPFC target will be determined using their resting state functional connectivity between anterior cingulate cortex and lDLPFC. Our algorithm performs a calculation of the individual localization of the participant's lDLPFC, which will be used for the whole study in that particular participant.</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Repetitive Transcranial Magnetic Stimulation</intervention_name>
      <description>The investigators will use a Magstim Rapid 2 stimulator, Airfilled coil (AFC), 8 shape (magnetic field of 0.8 Teslas, 3Kg, pulse 0.5 ms)&#xD;
  Each patient will receive high frequency 10 Hz stimulation at 100% of motor threshold over the dorsolateral prefrontal cortex (DLPFC) at 1500 pulses per session with 30 trains of 5 seconds and 0.5 ms stimuli and an inter-train distance of 15 seconds. In 2 daily sessions 4 days a week for 4 weeks.</description>
      <arm_group_label>Active rTMS frequency at 10 Hz</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Repetitive Transcranial Magnetic Stimulation (Sham)</intervention_name>
      <description>The investigators will use a Magstim Rapid 2 stimulator, Airfilled coil (AFC), 8 shape (magnetic field of 0.8 Teslas, 3Kg, pulse 0.5 ms)&#xD;
  Each patient will receive consistent treatment in 2 sessions a day for 20 consecutive business days for 4 weeks. The coil will be placed facing away from the skull to avoid an effect.</description>
      <arm_group_label>Sham rTMS frequency at 10 Hz</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Men and women of 25 to 59 years old&#xD;
  &#xD;
            -  The reading level of at least 6th grade of primary (equivalent to fifth grade of&#xD;
               elementary school).&#xD;
  &#xD;
            -  Alcohol users with and AUDIT ≥ 20 puntos&#xD;
  &#xD;
            -  Abstinence from alcohol consumption from 8 weeks to 5 years, with CIWA-Ar scale scores&#xD;
               ≤ 9 points.&#xD;
  &#xD;
            -  No disabling neuropsychiatric conditions&#xD;
  &#xD;
            -  No substance use disorders except alcohol and nicotine.&#xD;
  &#xD;
            -  BrAC (Breath Alcohol) = 0.00 mg/dl in each of the assessments.&#xD;
  &#xD;
            -  No traces of alcohol consumption using urine test strips.&#xD;
  &#xD;
            -  No contraindications for TMS therapy.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Individuals with symptoms of severe agitation or who are unable to cooperate in the&#xD;
               study&#xD;
  &#xD;
            -  History of epilepsy&#xD;
  &#xD;
            -  Sudden onset of stroke, focal neurological findings such as hemiparesis, sensory loss,&#xD;
               visual field deficits and lack of coordination.&#xD;
  &#xD;
            -  Seizures or gait disturbances&#xD;
  &#xD;
            -  History of severe psychiatric disorders.&#xD;
  &#xD;
            -  Alterations in a conventional electroencephalogram.&#xD;
  &#xD;
            -  Pacemakers or intracranial metallic objects.&#xD;
  &#xD;
          Elimination criteria&#xD;
  &#xD;
            -  At the subject's request&#xD;
  &#xD;
            -  The presence of adverse incidents that deteriorate the subject's health and would&#xD;
               limit continuation of rTMS treatment.&#xD;
  &#xD;
            -  Exacerbation of cognitive or behavioral symptoms during treatment.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>25 Years</minimum_age>
      <maximum_age>59 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Eduardo A Garza-Villarreal, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Universidad Nacional Autonoma de Mexico</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Alejandra Lopez Castro, MD, MSc</last_name>
      <phone>4422381038</phone>
      <email>alejandraloc@comunidad.unam.mx</email>
    </overall_contact>
    <location>
      <facility>
        <name>Unidad de Resonancia Magnética</name>
        <address>
          <city>Querétaro City</city>
          <state>Queretaro</state>
          <zip>76230</zip>
          <country>Mexico</country>
        </address>
      </facility>
      <contact>
        <last_name>Alejandra Lopez Castro, MD, MSc</last_name>
        <phone>4422381038</phone>
        <email>alejandraloc@comunidad.unam.mx</email>
      </contact>
      <investigator>
        <last_name>Eduardo A Garza Villarreal, MD, PhD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Mexico</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 10, 2023</study_first_submitted>
    <study_first_submitted_qc>August 10, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 18, 2023</study_first_posted>
    <last_update_submitted>August 10, 2023</last_update_submitted>
    <last_update_submitted_qc>August 10, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Universidad Nacional Autonoma de Mexico</investigator_affiliation>
      <investigator_full_name>Eduardo Adrian Garza Villarreal</investigator_full_name>
      <investigator_title>Assistant Professor</investigator_title>
    </responsible_party>
    <keyword>mri</keyword>
    <keyword>rtms</keyword>
    <keyword>tms</keyword>
    <keyword>repetitive transcranial magnetic stimulation</keyword>
    <keyword>mexico</keyword>
    <keyword>magnetic resonance imaging</keyword>
    <keyword>executive function</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Alcoholism</mesh_term>
      <mesh_term>Alcohol Drinking</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>All clinical and MRI data will be shared with each patient's written consent. Identification information will not be shared, only the RID, and all MRI structural data will be defaced prior to sharing. MRI data will be uploaded to Open Neuro while the clinical data will be uploaded to Zenodo.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Analytic Code</ipd_info_type>
      <ipd_time_frame>Data will be shared once the study is finished and published, aproximately in 2027</ipd_time_frame>
      <ipd_access_criteria>open access</ipd_access_criteria>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05997212
  org study id: 101.H
  nct id: NCT05997212
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  Alcohol Use Disorder (AUD) is a major public health problem that affects the physical,
        social, family, and mental integrity of the sufferer. Behavioral self-regulation is
        compromised in AUD, and a benefit has been reported with the application of repetitive
        transcranial magnetic stimulation and emotional self-regulation. The aim of this study is to
        investigate the efficacy of high-frequency rTMS to improve executive functions in patients in
        abstinence from AUD.
  It is proposed that people with a greater predisposition to develop AUD have alterations in
        executive functions, due to maladaptive cellular homeostatic processes and neuronal circuits
        stimulated by substances, and that these alterations persist even after the withdrawal of the
        substance (Nestler and Aghajanian, 1997). Also as a multifactorial disorder, it has been
        considered the implication of family history of consumption (Khemiri et al., 2020; Peterson
        et al., 1990 & Tarter et al., 1989) and individual traits, like poor performance on a
        cognitive test compared to controls, (Shnitko et al., 2018 & Goudriaan et al., 2011) as a
        predictor to develop heavy alcohol consumption or AUD. The alteration in executive functions
        seems to manifest with the perseverance of negative behaviors that prevent new forms of
        learning and adaptation to situations, and the decrease in the activation of the executive
        control network, which is correlated with the severity of the AUD (Mayhugh et al., 2014). One
        executive function that may be related to AUD and treatment success is cognitive flexibility,
        whose role is to allow thoughts and behaviors to be appropriately adjusted in response to
        environmental cognitive demands (Uddin., 2021). Studies have shown that the persistence and
        severity of AUD have been related to impaired cognitive flexibility (Stalnaker et al., 2008),
        and it is recovered after prolonged alcohol abstinence (Rourke & Grant, 1999). Therefore,
        cognitive flexibility may be a treatment biomarker worth exploring. According to a review by
        McLellan et al. (2000), 40 to 60 % of the patients who are treated for AUD relapse before the
        first year of follow-up after discharge. At least 60% of those treated for an AUD will
        relapse within 6 months of treatment (Durazzo and Meyerhoff, 2017; Kirshenbaum et al., 2009;
        Maisto et al., 2006a; Meyerhoff and Durazzo, 2010). It is for this reason that new treatments
        are still being sought in addition to standard pharmacological and psychotherapeutic
        treatments, where non-invasive neuromodulation techniques such as repetitive transcranial
        magnetic stimulation (rTMS) have shown promising results (Diana et al., 2017).
  
        The Food and Drug Administration (FDA) in 2020 approved the use of rTMS as a therapeutic
        option for nicotine use disorder, but not for AUD in which positive changes have been found.
        For example, Addolorato et al., (2017) used high frequency (10 Hz) rTMS in areas of the
        dorsolateral prefrontal cortex (DLPFC) in humans with AUD and found a reduction in alcohol
        consumption and an increase in the number of days of drinking abstinence. It has been found
        that rTMS on the left DLPC increased inhibitory control and selective attention, and reduced
        depressive and somatization features, in subjects with active alcohol consumption (Del Felice
        et al., 2016). Since DLPFC is an important region of the executive control network, rTMS in
        this region in patients with AUD could induce an increase in functional connectivity of this
        network and consequently increase cognitive flexibility. About the effects of rTMS on
        cognitive functions, it was found to increase inhibitory control and selective attention (Del
        Felice et al., 2016, Diana et al., 2017). For all the above, we proposed to conduct a
        longitudinal study that will assess the cognitive and behavioral characteristics of people
        with a history of AUD that could play in the first place a crucial part to have developed the
        disorder. And the effects of TMS on this population, using the non-invasive technique of MRI
        and the neuropsychological tool to assess the cognitive and behavioral effects.
  
        The aim of this study is to investigate the short- and long-term clinical and cognitive
        effects of repetitive transcranial magnetic stimulation (rTMS) at a frequency of 10 Hz on the
        left dorsolateral prefrontal cortex in patients with alcohol use disorder in abstinence and
        to examine possible changes in brain structure and functional connectivity associated with
        this intervention. To do this, the investigators will recruit alcohol-dependent patients and
        stimulate them by rTMS twice daily for 4 weeks. The investigators will follow the patients to
        determine clinical outcomes at 6 months. The investigators will also measure clinical,
        cognitive, structural, and functional brain connectivity to assess short- and long-term
        intervention-related changes (measurements at baseline, 4 weeks, and 6 months).
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Single-blind randomize clincial trial with parallel groups
  primary purpose: Treatment
  masking: Single (Participant)
  masking description: Single blind. The participants will be the only ones blinded. The rTMS coil will be put backwards in the Sham group.
  measure: Change in Wisconsin Card Sorting Task
  time frame: Baseline, 4 weeks, 6 months
  description: Measured by Wisconsin Card Sorting Task (WCST) to evaluate cognitive flexibility
  measure: Change STROOP effect
  time frame: Baseline, 4 weeks, 6 months
  description: Measured by STROOP test to evaluate control inhibition
  measure: Change Visoespatial Memory
  time frame: Baseline, 4 weeks, 6 months
  description: Measured by Visoespatial Memory test to evaluate visoespatial memory
  measure: Change in Taskswitching Task Switch cost
  time frame: Baseline, 4 weeks
  description: Measured by Taskswitching task to evaluate cognitive flexibility
  measure: Change in Flanker Task Flanker Efect
  time frame: Baseline, 4 weeks
  description: Measured by Flanker task to evaluate control inhibition
  measure: Change in Nback Task accuracy
  time frame: Baseline, 4 weeks
  description: Measured by Nback task to evaluate working memory
  measure: Change in Alcohol Craving (VAS)
  time frame: Baseline, 4 weeks, 6 months
  description: The craving will be measured using a 100 mm visual analogue scales
  measure: Changes in psychopathological symptoms
  time frame: Baseline, 4 weeks, 6 months
  description: Measured by the Symptoms Questionnaire 90 (SCL-90)
  measure: Changes in WHODAS score
  time frame: Baseline, 4 weeks, 6 months
  description: Measured by Disability Assessment Schedule (WHODAS)
  measure: Changes in Anxiety
  time frame: Baseline, 4 weeks, 6 months
  description: Measured by Hamilton Anxiety Rating Scale (HARS)
  measure: Changes in Depression
  time frame: Baseline, 4 weeks, 6 months
  description: Measured by Hamilton Depression Rating Scale (HDRS)
  measure: Changes in functional connectivity
  time frame: Baseline, 4 weeks
  description: Functional connectivity of the dorsolateral prefrontal with the anterior cingulate cortex, measured with fMRI defined by the temporal correlation in the blood-oxygen-level-dependent signals of the regions. Higher correlations indicate stronger functional connectivity.
  arm group label: Active rTMS frequency at 10 Hz
  arm group type: Experimental
  description: The intervention will be Repetitive Transcranial Magnetic Stimulation. Each patient will receive treatment stimulation in the left dorsolateral prefrontal cortex (lDLPFC) with a frequency of 10 Hz, that includes 2 sessions per day for 20 consecutive business days for 4 weeks. Each session will consist of the application of rTMS at a frequency of 10 Hz, to 100% of the motor threshold. The lDLPFC target will be determined using their resting state functional connectivity between anterior cingulate cortex and lDLPFC. Our algorithm performs a calculation of the individual localization of the participant's lDLPFC, which will be used for the whole study in that particular participant.
  arm group label: Sham rTMS frequency at 10 Hz
  arm group type: Sham Comparator
  description: The intervention will be Repetitive Transcranial Magnetic Stimulation (Sham). For this patients the coil will be located backwards to the skull. Each patient will receive sham stimulation in the left dorsolateral prefrontal cortex (lDLPFC) with a frequency of 10 Hz, that includes 2 sessions per day for 20 consecutive business days for 4 weeks. Each session will consist of the application of rTMS at a frequency of 10 Hz, to 100% of the motor threshold. The lDLPFC target will be determined using their resting state functional connectivity between anterior cingulate cortex and lDLPFC. Our algorithm performs a calculation of the individual localization of the participant's lDLPFC, which will be used for the whole study in that particular participant.
  intervention type: Device
  intervention name: Repetitive Transcranial Magnetic Stimulation
  description: The investigators will use a Magstim Rapid 2 stimulator, Airfilled coil (AFC), 8 shape (magnetic field of 0.8 Teslas, 3Kg, pulse 0.5 ms)
  Each patient will receive high frequency 10 Hz stimulation at 100% of motor threshold over the dorsolateral prefrontal cortex (DLPFC) at 1500 pulses per session with 30 trains of 5 seconds and 0.5 ms stimuli and an inter-train distance of 15 seconds. In 2 daily sessions 4 days a week for 4 weeks.
  arm group label: Active rTMS frequency at 10 Hz
  intervention type: Device
  intervention name: Repetitive Transcranial Magnetic Stimulation (Sham)
  description: The investigators will use a Magstim Rapid 2 stimulator, Airfilled coil (AFC), 8 shape (magnetic field of 0.8 Teslas, 3Kg, pulse 0.5 ms)
  Each patient will receive consistent treatment in 2 sessions a day for 20 consecutive business days for 4 weeks. The coil will be placed facing away from the skull to avoid an effect.
  arm group label: Sham rTMS frequency at 10 Hz
  criteria: 
  gender: All
  minimum age: 25 Years
  maximum age: 59 Years
  healthy volunteers: No
  last name: Eduardo A Garza-Villarreal, MD, PhD
  role: Principal Investigator
  affiliation: Universidad Nacional Autonoma de Mexico
  last name: Alejandra Lopez Castro, MD, MSc
  phone: 4422381038
  email: alejandraloc@comunidad.unam.mx
  facility: 
  contact: 
  investigator: 
  country: Mexico
  responsible party type: Principal Investigator
  investigator affiliation: Universidad Nacional Autonoma de Mexico
  investigator full name: Eduardo Adrian Garza Villarreal
  investigator title: Assistant Professor
  mesh term: Alcoholism
  mesh term: Alcohol Drinking
  sharing ipd: Yes
  ipd description: All clinical and MRI data will be shared with each patient's written consent. Identification information will not be shared, only the RID, and all MRI structural data will be defaced prior to sharing. MRI data will be uploaded to Open Neuro while the clinical data will be uploaded to Zenodo.
  ipd info type: Study Protocol
  ipd info type: Analytic Code
  ipd time frame: Data will be shared once the study is finished and published, aproximately in 2027
  ipd access criteria: open access