<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/NCT03018236</url>
  </required_header>
  <id_info>
    <org_study_id>150488</org_study_id>
    <nct_id>NCT03018236</nct_id>
  </id_info>
  <brief_title>Effect of N-acetylcysteine on Alcohol and Cocaine Use Disorders: A Double-Blind Randomized Controlled Trial.</brief_title>
  <official_title>The Effect of N-acetylcysteine (NAC) on Treatment of Alcohol and Cocaine Use Disorders: A Double-Blind Randomized Controlled Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital de Clinicas de Porto Alegre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Secretaria Nacional de Políticas sobre Drogas (SENAD)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hospital de Clinicas de Porto Alegre</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates the use of N-acetylcysteine in the treatment of alcohol and cocaine use&#xD;
      disorders. Alcohol users will be split in two groups, one will receive the active&#xD;
      N-acetylcysteine and the other placebo. The same division will occur with cocaine users. The&#xD;
      effects of N-acetylcysteine in adherence, abstinence, psychiatric symptoms and stress&#xD;
      biomarkers will be evaluated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      N-acetylcysteine acts replenishing the human body glutathione storages. Glutathione is an&#xD;
      important antioxidant agent, and also modulates the N-methyl-D-aspartate (NMDA) glutamatergic&#xD;
      receptor. Glutamate has been associated with the neuroadaptation related to substance use&#xD;
      disorders, and thus it is considered a potential target for pharmacological interventions&#xD;
      regarding these disorders. N-acetylcysteine also interacts with the cystine-glutamate&#xD;
      antiporter on astrocytes hence increasing glutamate release into the extracellular space.&#xD;
&#xD;
      N-acetylcysteine effects and its implications in the addiction disorders have been studied&#xD;
      initially with animal models. Glutamate levels normalization through N-acetylcysteine reduced&#xD;
      compulsive drug self-administration and drug-seeking behavior in mice. In addition, there are&#xD;
      promising results also with human subjects, showing benefits for cocaine, alcohol and&#xD;
      cannabis use disorders.&#xD;
&#xD;
      This study consists of a randomized, double-blind, placebo controlled trial with four arms:&#xD;
      alcohol users divided into NAC vs Placebo and cocaine users divided into NAC vs Placebo.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>January 2017</start_date>
  <completion_date type="Anticipated">December 2018</completion_date>
  <primary_completion_date type="Anticipated">July 2018</primary_completion_date>
  <phase>Phase 4</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants who attended all study appointments</measure>
    <time_frame>8 weeks</time_frame>
    <description>Completers (i.e. subjects who attended all study appointments) vs non-completers</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Abstinence by urine</measure>
    <time_frame>8 weeks</time_frame>
    <description>Amount of positive urine tests for cocaine users</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Abstinence by breathalyzer</measure>
    <time_frame>8 weeks</time_frame>
    <description>Amount of positive breathalyzer tests for alcohol users</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Abstinence by self report</measure>
    <time_frame>8 weeks</time_frame>
    <description>Timeline Followback Method</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days of inpatient treatment</measure>
    <time_frame>Up to 4 weeks</time_frame>
    <description>The difference (if any) between placebo and intervention groups in the amount of inpatient treatment days.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in scores of CGI</measure>
    <time_frame>8 weeks</time_frame>
    <description>Differences in scores of the Clinical Global Impression (CGI)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in scores of FAST</measure>
    <time_frame>8 weeks</time_frame>
    <description>Differences in scores of the Functioning Assessment Short Test (FAST).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Depressive symptoms</measure>
    <time_frame>8 weeks</time_frame>
    <description>Differences in scores of the Beck Depression Inventory (BDI)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anxiety symptoms</measure>
    <time_frame>8 weeks</time_frame>
    <description>Differences in scores of the Beck Anxiety Inventory (BAI)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BDNF</measure>
    <time_frame>8 weeks</time_frame>
    <description>Differences between groups regarding dosage of Brain Derived Neurotrophic Factor (BDNF)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>GSSG</measure>
    <time_frame>8 weeks</time_frame>
    <description>Differences between groups regarding dosage of Oxidized Glutathione (GSSG)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>GSH</measure>
    <time_frame>8 weeks</time_frame>
    <description>Differences between groups regarding dosage of Glutathione (GSH)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>GPx</measure>
    <time_frame>8 weeks</time_frame>
    <description>Differences between groups regarding dosage of Glutathione Peroxidase (GPx)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CAT</measure>
    <time_frame>8 weeks</time_frame>
    <description>Differences between groups regarding dosage of Catalase (CAT)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TBARS</measure>
    <time_frame>8 weeks</time_frame>
    <description>Differences between groups regarding dosage of Thiobarbituric Acid Reactive Substances (TBARS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SOD</measure>
    <time_frame>8 weeks</time_frame>
    <description>Differences between groups regarding dosage of Superoxide Dismutase (SOD)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Carbonyl</measure>
    <time_frame>8 weeks</time_frame>
    <description>Differences between groups regarding dosage of Carbonyl</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Adverse events</measure>
    <time_frame>8 weeks</time_frame>
    <description>Systematic Assessment for Treatment Emergent Events (SAFTEE) application</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Cocaine Addiction</condition>
  <condition>Alcohol Addiction</condition>
  <arm_group>
    <arm_group_label>Alcohol N-acetylcysteine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>600 mg N-acetylcysteine capsule by mouth, every 12 hours for 8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Alcohol Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>A placebo capsule matching color and smell of the active medication</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cocaine N-acetylcysteine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>600 mg N-acetylcysteine capsule by mouth, every 12 hours for 8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cocaine Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>A placebo capsule matching color and smell of the active medication</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alcohol N-acetylcysteine</intervention_name>
    <description>1200 mg of NAC per day, taken in two doses, for subjects with alcohol use disorder</description>
    <arm_group_label>Alcohol N-acetylcysteine</arm_group_label>
    <other_name>NAC</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alcohol Placebo</intervention_name>
    <description>Flour pills looking exactly the same as the active compound, for subjects with alcohol use disorder</description>
    <arm_group_label>Alcohol Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cocaine N-acetylcysteine</intervention_name>
    <description>1200 mg of NAC per day, taken in two doses, for subjects with cocaine use disorder</description>
    <arm_group_label>Cocaine N-acetylcysteine</arm_group_label>
    <other_name>NAC</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cocaine Placebo</intervention_name>
    <description>Flour pills looking exactly the same as the active compound, for subjects with cocaine use disorder</description>
    <arm_group_label>Cocaine Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnostic of Alcohol or Cocaine Use Disorder&#xD;
&#xD;
          -  Seven days of inpatient treatment in an addiction treatment specialized unit&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Another Substance Use Disorder (exception: tobacco)&#xD;
&#xD;
          -  Severe medical conditions (cardiac, renal or hepatic), that preclude subject&#xD;
             participation&#xD;
&#xD;
          -  History of asthma or convulsions medication use&#xD;
&#xD;
          -  Recent use (&lt;14 days) of any medication that could interfere with the study medication&#xD;
&#xD;
          -  History of anaphylactic reactions with the study medication&#xD;
&#xD;
          -  Suicide risk&#xD;
&#xD;
          -  Inability to understand the informed consent form or to comply with the study&#xD;
             requirements&#xD;
&#xD;
          -  Any severe neuropsychiatric condition, not caused by the substance use, that requires&#xD;
             specific medication treatments and could interfere with the study development, in the&#xD;
             investigators opinion (for instance: dementia, schizophrenia or other psychoses,&#xD;
             multiple sclerosis, severe depression, stroke, epilepsy, bipolar disorder)&#xD;
&#xD;
          -  Failing to complete the screening procedures prior to the study first week&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lisia von Diemen, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Federal University of Rio Grande do Sul (UFRGS)</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Flavio Pechansky, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Federal University of Rio Grande do Sul (UFRGS)</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Lisia von Diemen, PhD</last_name>
    <phone>+55 51 3359 6471</phone>
    <email>lisiavd@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Thiago C Hartmann, MsC</last_name>
    <phone>+55 51 3359 6476</phone>
    <email>hartmann321@yahoo.com.br</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hospital de Clinicas de Porto Alegre - Unidade Alvaro Alvim</name>
      <address>
        <city>Porto Alegre</city>
        <state>RS</state>
        <zip>90420-020</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Thiago C Hartmann, MsC</last_name>
      <phone>+55 51 3359 6476</phone>
      <email>hartmann321@yahoo.com.br</email>
    </contact>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
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  <verification_date>January 2017</verification_date>
  <study_first_submitted>January 10, 2017</study_first_submitted>
  <study_first_submitted_qc>January 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 11, 2017</study_first_posted>
  <last_update_submitted>January 20, 2017</last_update_submitted>
  <last_update_submitted_qc>January 20, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 24, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>cocaine</keyword>
  <keyword>alcohol</keyword>
  <keyword>substance use disorders</keyword>
  <keyword>addiction</keyword>
  <keyword>N-acetylcysteine</keyword>
  <keyword>randomized controlled trial</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cocaine-Related Disorders</mesh_term>
    <mesh_term>Alcoholism</mesh_term>
    <mesh_term>Behavior, Addictive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ethanol</mesh_term>
    <mesh_term>Acetylcysteine</mesh_term>
    <mesh_term>Cocaine</mesh_term>
    <mesh_term>N-monoacetylcystine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT03018236
org study id: 150488
nct id: NCT03018236
lead sponsor: 
collaborator: 
has dmc: No
This study evaluates the use of N-acetylcysteine in the treatment of alcohol and cocaine use
      disorders. Alcohol users will be split in two groups, one will receive the active
      N-acetylcysteine and the other placebo. The same division will occur with cocaine users. The
      effects of N-acetylcysteine in adherence, abstinence, psychiatric symptoms and stress
      biomarkers will be evaluated.
N-acetylcysteine acts replenishing the human body glutathione storages. Glutathione is an
      important antioxidant agent, and also modulates the N-methyl-D-aspartate (NMDA) glutamatergic
      receptor. Glutamate has been associated with the neuroadaptation related to substance use
      disorders, and thus it is considered a potential target for pharmacological interventions
      regarding these disorders. N-acetylcysteine also interacts with the cystine-glutamate
      antiporter on astrocytes hence increasing glutamate release into the extracellular space.

      N-acetylcysteine effects and its implications in the addiction disorders have been studied
      initially with animal models. Glutamate levels normalization through N-acetylcysteine reduced
      compulsive drug self-administration and drug-seeking behavior in mice. In addition, there are
      promising results also with human subjects, showing benefits for cocaine, alcohol and
      cannabis use disorders.

      This study consists of a randomized, double-blind, placebo controlled trial with four arms:
      alcohol users divided into NAC vs Placebo and cocaine users divided into NAC vs Placebo.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of participants who attended all study appointments
time frame: 8 weeks
description: Completers (i.e. subjects who attended all study appointments) vs non-completers
measure: Abstinence by urine
time frame: 8 weeks
description: Amount of positive urine tests for cocaine users
measure: Abstinence by breathalyzer
time frame: 8 weeks
description: Amount of positive breathalyzer tests for alcohol users
measure: Abstinence by self report
time frame: 8 weeks
description: Timeline Followback Method
measure: Days of inpatient treatment
time frame: Up to 4 weeks
description: The difference (if any) between placebo and intervention groups in the amount of inpatient treatment days.
measure: Change in scores of CGI
time frame: 8 weeks
description: Differences in scores of the Clinical Global Impression (CGI)
measure: Change in scores of FAST
time frame: 8 weeks
description: Differences in scores of the Functioning Assessment Short Test (FAST).
measure: Depressive symptoms
time frame: 8 weeks
description: Differences in scores of the Beck Depression Inventory (BDI)
measure: Anxiety symptoms
time frame: 8 weeks
description: Differences in scores of the Beck Anxiety Inventory (BAI)
measure: BDNF
time frame: 8 weeks
description: Differences between groups regarding dosage of Brain Derived Neurotrophic Factor (BDNF)
measure: GSSG
time frame: 8 weeks
description: Differences between groups regarding dosage of Oxidized Glutathione (GSSG)
measure: GSH
time frame: 8 weeks
description: Differences between groups regarding dosage of Glutathione (GSH)
measure: GPx
time frame: 8 weeks
description: Differences between groups regarding dosage of Glutathione Peroxidase (GPx)
measure: CAT
time frame: 8 weeks
description: Differences between groups regarding dosage of Catalase (CAT)
measure: TBARS
time frame: 8 weeks
description: Differences between groups regarding dosage of Thiobarbituric Acid Reactive Substances (TBARS)
measure: SOD
time frame: 8 weeks
description: Differences between groups regarding dosage of Superoxide Dismutase (SOD)
measure: Carbonyl
time frame: 8 weeks
description: Differences between groups regarding dosage of Carbonyl
measure: Adverse events
time frame: 8 weeks
description: Systematic Assessment for Treatment Emergent Events (SAFTEE) application
arm group label: Alcohol N-acetylcysteine
arm group type: Experimental
description: 600 mg N-acetylcysteine capsule by mouth, every 12 hours for 8 weeks
arm group label: Alcohol Placebo
arm group type: Placebo Comparator
description: A placebo capsule matching color and smell of the active medication
arm group label: Cocaine N-acetylcysteine
arm group type: Experimental
description: 600 mg N-acetylcysteine capsule by mouth, every 12 hours for 8 weeks
arm group label: Cocaine Placebo
arm group type: Placebo Comparator
description: A placebo capsule matching color and smell of the active medication
intervention type: Drug
intervention name: Alcohol N-acetylcysteine
description: 1200 mg of NAC per day, taken in two doses, for subjects with alcohol use disorder
arm group label: Alcohol N-acetylcysteine
other name: NAC
intervention type: Drug
intervention name: Alcohol Placebo
description: Flour pills looking exactly the same as the active compound, for subjects with alcohol use disorder
arm group label: Alcohol Placebo
intervention type: Drug
intervention name: Cocaine N-acetylcysteine
description: 1200 mg of NAC per day, taken in two doses, for subjects with cocaine use disorder
arm group label: Cocaine N-acetylcysteine
other name: NAC
intervention type: Drug
intervention name: Cocaine Placebo
description: Flour pills looking exactly the same as the active compound, for subjects with cocaine use disorder
arm group label: Cocaine Placebo
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Lisia von Diemen, PhD
role: Study Chair
affiliation: Federal University of Rio Grande do Sul (UFRGS)
last name: Flavio Pechansky, PhD
role: Principal Investigator
affiliation: Federal University of Rio Grande do Sul (UFRGS)
last name: Lisia von Diemen, PhD
phone: +55 51 3359 6471
email: lisiavd@gmail.com
last name: Thiago C Hartmann, MsC
phone: +55 51 3359 6476
email: hartmann321@yahoo.com.br
facility: 
status: Recruiting
contact: 
country: Brazil
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responsible party type: Sponsor
mesh term: Cocaine-Related Disorders
mesh term: Alcoholism
mesh term: Behavior, Addictive
mesh term: Ethanol
mesh term: Acetylcysteine
mesh term: Cocaine
mesh term: N-monoacetylcystine
sharing ipd: Undecided