<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/NCT04405193</url>
  </required_header>
  <id_info>
    <org_study_id>UI-BNN</org_study_id>
    <nct_id>NCT04405193</nct_id>
  </id_info>
  <brief_title>The Efficacy of N-acetylcysteine Versus Placebo for the Treatment of Metamphetamine Withdrawal Symptoms</brief_title>
  <official_title>The Efficacy of N-acetylcysteine Versus Placebo for the Treatment of Metamphetamine Withdrawal Symptoms</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Melva Louisa</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Indonesia University</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Up to date, no approved medications are available for the treatment of methamphetamine&#xD;
      addiction. Recently, N-acetylcysteine is recently being studied for methamphetamine&#xD;
      withdrawal.&#xD;
&#xD;
      N-acetylcysteine, is a drug that has been long used as a mucolytic. Recent studies&#xD;
      investigate the use of N-acetylcysteine in cocaine and withdrawal symptoms by its effect on&#xD;
      restoring glutamate homeostasis in nucleus accumbens. Up to date, there has been 2 pilot&#xD;
      study investigating the efficacy of N-acetylcysteine for methamphetamine dependence.&#xD;
&#xD;
      The present study is aimed to confirm the efficacy and safety of N-acetylcysteine in the&#xD;
      treatment of methamphetamine withdrawal symptoms.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Methamphetamine is a stimulant commonly abused worldwide. Methamphetamine can produce a rapid&#xD;
      pleasurable rush caused by release of dopamine, nor-ephinephrine and serotonin. It produces&#xD;
      euphoria, a heightened level of alertness and increased level of alertness and increased&#xD;
      energy. Long-term regular meth use can lead to severe tooth decay, infection, weight loss,&#xD;
      malnutrition, kidney damage, liver damage, respiratory issues, paranoia, violent behaviour,&#xD;
      psychosis, severe anxiety and depression.&#xD;
&#xD;
      Studies suggested that withdrawal symptoms in methamphetamine dependent patients were due to&#xD;
      the state of hypodopaminergic activities.&#xD;
&#xD;
      Up to date, no approved medications are available for the treatment of methamphetamine&#xD;
      addiction. Recently, N-acetylcysteine is recently being studied for methamphetamine&#xD;
      withdrawal.&#xD;
&#xD;
      N-acetylcysteine, is a drug that has been long used as a mucolytic. Up to date, there has&#xD;
      been 2 pilot study investigating the efficacy of N-acetylcysteine for methamphetamine&#xD;
      dependence. The present study is aimed to confirm the efficacy and safety of N-acetylcysteine&#xD;
      in the treatment of methamphetamine withdrawal symptoms.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2019</start_date>
  <completion_date type="Actual">December 30, 2020</completion_date>
  <primary_completion_date type="Actual">July 30, 2020</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Randomised, parallel, 4 week-treatment of N-acetylcysteine versus matching placebo</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>Matching placebo</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Methamphetamine withdrawal symptoms in patients treated with N-acetylcysteine vs placebo</measure>
    <time_frame>Change from baseline at 1 week.</time_frame>
    <description>Withdrawal symptoms will be measured using Addiction Severity Index (ASI). ASI score ranged from 0 to 9, with score of 0 indicates no withdrawal symptoms and 9 indicates extreme symptoms of withdrawal symptoms</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Methamphetamine withdrawal symptoms in patients treated with N-acetylcysteine vs placebo</measure>
    <time_frame>Change from baseline at 2 weeks</time_frame>
    <description>Withdrawal symptoms will be measured using Addiction Severity Index (ASI). ASI score ranged from 0 to 9, with score of 0 indicates no withdrawal symptoms and 9 indicates extreme symptoms of withdrawal symptoms</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Methamphetamine withdrawal symptoms in patients treated with N-acetylcysteine vs placebo</measure>
    <time_frame>Change from baseline at 4 weeks</time_frame>
    <description>Withdrawal symptoms will be measured using Addiction Severity Index (ASI). ASI score ranged from 0 to 9, with score of 0 indicates no withdrawal symptoms and 9 indicates extreme symptoms of withdrawal symptoms</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Antioxidative effects of N-acetylcysteine vs placebo</measure>
    <time_frame>Change from baseline at 4 weeks</time_frame>
    <description>antioxidative effects will be measured by quantifying malondialdehyde plasma concentrations (micromol/L).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of N-acetylcysteine vs placebo</measure>
    <time_frame>Subjects with adverse events at week 1</time_frame>
    <description>The number of subjects with adverse events at week 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of N-acetylcysteine vs placebo</measure>
    <time_frame>Subjects with adverse events at week 2</time_frame>
    <description>The number of subjects with adverse events at week 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of N-acetylcysteine vs placebo</measure>
    <time_frame>Subjects with adverse events at week 4</time_frame>
    <description>The number of subjects with adverse events at week 4</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">66</enrollment>
  <condition>Methamphetamine Dependence in Remission</condition>
  <arm_group>
    <arm_group_label>Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2 capsules, each containing 600 mg N-acetylcysteine administered once daily every morning.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>2 capsules of matching placebo administered once daily every morning</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>N-acetyl cysteine</intervention_name>
    <description>Eligible patients will be randomised to receive N-acetylcysteine or placebo</description>
    <arm_group_label>Treatment</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matching Placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men or women, 18 - 60 years old&#xD;
&#xD;
          -  Diagnosed with methamphetamine addiction based on DSM-V criteria, enrolling for&#xD;
             methamphetamine withdrawal treatment&#xD;
&#xD;
          -  Agree to participate in the trial by signing informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known hypersensitivity to N-acetylcysteine&#xD;
&#xD;
          -  Patients with serious conditions that will not allow protocol compliance or safe&#xD;
             participation in the clinical trials.&#xD;
&#xD;
          -  Pregnant or breastfeeding women&#xD;
&#xD;
          -  History of suicidal thoughts / behaviour&#xD;
&#xD;
          -  History of N-acetylcysteine treatment&#xD;
&#xD;
          -  History of asthma and convulsions&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Erniawati Lestari, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Indonesia University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rehabilitation Center, National Narcotics Agency</name>
      <address>
        <city>Bogor</city>
        <state>West Java</state>
        <zip>16110</zip>
        <country>Indonesia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Indonesia</country>
  </location_countries>
  <reference>
    <citation>Ling W, Mooney L, Haglund M. Treating methamphetamine abuse disorders. Curr Psychiatry. 2014; 13(9): 37 - 44.</citation>
  </reference>
  <reference>
    <citation>Winslow BT, Voorhees KI, Pehl KA. Methamphetamine abuse. Am Fam Physician. 2007 Oct 15;76(8):1169-74.</citation>
    <PMID>17990840</PMID>
  </reference>
  <reference>
    <citation>Prakash MD, Tangalakis K, Antonipillai J, Stojanovska L, Nurgali K, Apostolopoulos V. Methamphetamine: Effects on the brain, gut and immune system. Pharmacol Res. 2017 Jun;120:60-67. doi: 10.1016/j.phrs.2017.03.009. Epub 2017 Mar 14.</citation>
    <PMID>28302577</PMID>
  </reference>
  <reference>
    <citation>Ballester J, Valentine G, Sofuoglu M. Pharmacological treatments for methamphetamine addiction: current status and future directions. Expert Rev Clin Pharmacol. 2017 Mar;10(3):305-314. doi: 10.1080/17512433.2017.1268916. Epub 2016 Dec 20.</citation>
    <PMID>27927042</PMID>
  </reference>
  <reference>
    <citation>McKetin R, Dean OM, Baker AL, Carter G, Turner A, Kelly PJ, Berk M. A potential role for N-acetylcysteine in the management of methamphetamine dependence. Drug Alcohol Rev. 2017 Mar;36(2):153-159. doi: 10.1111/dar.12414. Epub 2016 May 30.</citation>
    <PMID>27241765</PMID>
  </reference>
  <reference>
    <citation>Nocito Echevarria MA, Andrade Reis T, Ruffo Capatti G, Siciliano Soares V, da Silveira DX, Fidalgo TM. N-acetylcysteine for treating cocaine addiction - A systematic review. Psychiatry Res. 2017 May;251:197-203. doi: 10.1016/j.psychres.2017.02.024. Epub 2017 Feb 11.</citation>
    <PMID>28213190</PMID>
  </reference>
  <reference>
    <citation>Grant JE, Odlaug BL, Kim SW. A double-blind, placebo-controlled study of N-acetyl cysteine plus naltrexone for methamphetamine dependence. Eur Neuropsychopharmacol. 2010 Nov;20(11):823-8. doi: 10.1016/j.euroneuro.2010.06.018. Epub 2010 Jul 22.</citation>
    <PMID>20655182</PMID>
  </reference>
  <reference>
    <citation>Mousavi SG, Sharbafchi MR, Salehi M, Peykanpour M, Karimian Sichani N, Maracy M. The efficacy of N-acetylcysteine in the treatment of methamphetamine dependence: a double-blind controlled, crossover study. Arch Iran Med. 2015 Jan;18(1):28-33.</citation>
    <PMID>25556383</PMID>
  </reference>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>April 21, 2020</study_first_submitted>
  <study_first_submitted_qc>May 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 28, 2020</study_first_posted>
  <last_update_submitted>February 9, 2021</last_update_submitted>
  <last_update_submitted_qc>February 9, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 10, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Indonesia University</investigator_affiliation>
    <investigator_full_name>Melva Louisa</investigator_full_name>
    <investigator_title>Dr Melva Louisa, SSi, MBiomed; Research Coordinator for the Department of Pharmacology and Therapeutics, Primary Investigator</investigator_title>
  </responsible_party>
  <keyword>methamphetamine</keyword>
  <keyword>N-acetylcysteine</keyword>
  <keyword>substance abuse</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Substance Withdrawal Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetylcysteine</mesh_term>
    <mesh_term>N-monoacetylcystine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>The results will be published in peer-reviewed journal</ipd_description>
  </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/NCT04405193
org study id: UI-BNN
nct id: NCT04405193
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Up to date, no approved medications are available for the treatment of methamphetamine
      addiction. Recently, N-acetylcysteine is recently being studied for methamphetamine
      withdrawal.

      N-acetylcysteine, is a drug that has been long used as a mucolytic. Recent studies
      investigate the use of N-acetylcysteine in cocaine and withdrawal symptoms by its effect on
      restoring glutamate homeostasis in nucleus accumbens. Up to date, there has been 2 pilot
      study investigating the efficacy of N-acetylcysteine for methamphetamine dependence.

      The present study is aimed to confirm the efficacy and safety of N-acetylcysteine in the
      treatment of methamphetamine withdrawal symptoms.
Methamphetamine is a stimulant commonly abused worldwide. Methamphetamine can produce a rapid
      pleasurable rush caused by release of dopamine, nor-ephinephrine and serotonin. It produces
      euphoria, a heightened level of alertness and increased level of alertness and increased
      energy. Long-term regular meth use can lead to severe tooth decay, infection, weight loss,
      malnutrition, kidney damage, liver damage, respiratory issues, paranoia, violent behaviour,
      psychosis, severe anxiety and depression.

      Studies suggested that withdrawal symptoms in methamphetamine dependent patients were due to
      the state of hypodopaminergic activities.

      Up to date, no approved medications are available for the treatment of methamphetamine
      addiction. Recently, N-acetylcysteine is recently being studied for methamphetamine
      withdrawal.

      N-acetylcysteine, is a drug that has been long used as a mucolytic. Up to date, there has
      been 2 pilot study investigating the efficacy of N-acetylcysteine for methamphetamine
      dependence. The present study is aimed to confirm the efficacy and safety of N-acetylcysteine
      in the treatment of methamphetamine withdrawal symptoms.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomised, parallel, 4 week-treatment of N-acetylcysteine versus matching placebo
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: Matching placebo
measure: Methamphetamine withdrawal symptoms in patients treated with N-acetylcysteine vs placebo
time frame: Change from baseline at 1 week.
description: Withdrawal symptoms will be measured using Addiction Severity Index (ASI). ASI score ranged from 0 to 9, with score of 0 indicates no withdrawal symptoms and 9 indicates extreme symptoms of withdrawal symptoms
measure: Methamphetamine withdrawal symptoms in patients treated with N-acetylcysteine vs placebo
time frame: Change from baseline at 2 weeks
description: Withdrawal symptoms will be measured using Addiction Severity Index (ASI). ASI score ranged from 0 to 9, with score of 0 indicates no withdrawal symptoms and 9 indicates extreme symptoms of withdrawal symptoms
measure: Methamphetamine withdrawal symptoms in patients treated with N-acetylcysteine vs placebo
time frame: Change from baseline at 4 weeks
description: Withdrawal symptoms will be measured using Addiction Severity Index (ASI). ASI score ranged from 0 to 9, with score of 0 indicates no withdrawal symptoms and 9 indicates extreme symptoms of withdrawal symptoms
measure: Antioxidative effects of N-acetylcysteine vs placebo
time frame: Change from baseline at 4 weeks
description: antioxidative effects will be measured by quantifying malondialdehyde plasma concentrations (micromol/L).
measure: Safety of N-acetylcysteine vs placebo
time frame: Subjects with adverse events at week 1
description: The number of subjects with adverse events at week 1
measure: Safety of N-acetylcysteine vs placebo
time frame: Subjects with adverse events at week 2
description: The number of subjects with adverse events at week 2
measure: Safety of N-acetylcysteine vs placebo
time frame: Subjects with adverse events at week 4
description: The number of subjects with adverse events at week 4
arm group label: Treatment
arm group type: Experimental
description: 2 capsules, each containing 600 mg N-acetylcysteine administered once daily every morning.
arm group label: Placebo
arm group type: Placebo Comparator
description: 2 capsules of matching placebo administered once daily every morning
intervention type: Drug
intervention name: N-acetyl cysteine
description: Eligible patients will be randomised to receive N-acetylcysteine or placebo
arm group label: Treatment
other name: Placebo
intervention type: Drug
intervention name: Placebo
description: Matching Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Erniawati Lestari, MD
role: Study Chair
affiliation: Indonesia University
facility: 
country: Indonesia
citation: Ling W, Mooney L, Haglund M. Treating methamphetamine abuse disorders. Curr Psychiatry. 2014; 13(9): 37 - 44.
citation: Winslow BT, Voorhees KI, Pehl KA. Methamphetamine abuse. Am Fam Physician. 2007 Oct 15;76(8):1169-74.
PMID: 17990840
citation: Prakash MD, Tangalakis K, Antonipillai J, Stojanovska L, Nurgali K, Apostolopoulos V. Methamphetamine: Effects on the brain, gut and immune system. Pharmacol Res. 2017 Jun;120:60-67. doi: 10.1016/j.phrs.2017.03.009. Epub 2017 Mar 14.
PMID: 28302577
citation: Ballester J, Valentine G, Sofuoglu M. Pharmacological treatments for methamphetamine addiction: current status and future directions. Expert Rev Clin Pharmacol. 2017 Mar;10(3):305-314. doi: 10.1080/17512433.2017.1268916. Epub 2016 Dec 20.
PMID: 27927042
citation: McKetin R, Dean OM, Baker AL, Carter G, Turner A, Kelly PJ, Berk M. A potential role for N-acetylcysteine in the management of methamphetamine dependence. Drug Alcohol Rev. 2017 Mar;36(2):153-159. doi: 10.1111/dar.12414. Epub 2016 May 30.
PMID: 27241765
citation: Nocito Echevarria MA, Andrade Reis T, Ruffo Capatti G, Siciliano Soares V, da Silveira DX, Fidalgo TM. N-acetylcysteine for treating cocaine addiction - A systematic review. Psychiatry Res. 2017 May;251:197-203. doi: 10.1016/j.psychres.2017.02.024. Epub 2017 Feb 11.
PMID: 28213190
citation: Grant JE, Odlaug BL, Kim SW. A double-blind, placebo-controlled study of N-acetyl cysteine plus naltrexone for methamphetamine dependence. Eur Neuropsychopharmacol. 2010 Nov;20(11):823-8. doi: 10.1016/j.euroneuro.2010.06.018. Epub 2010 Jul 22.
PMID: 20655182
citation: Mousavi SG, Sharbafchi MR, Salehi M, Peykanpour M, Karimian Sichani N, Maracy M. The efficacy of N-acetylcysteine in the treatment of methamphetamine dependence: a double-blind controlled, crossover study. Arch Iran Med. 2015 Jan;18(1):28-33.
PMID: 25556383
responsible party type: Sponsor-Investigator
investigator affiliation: Indonesia University
investigator full name: Melva Louisa
investigator title: Dr Melva Louisa, SSi, MBiomed; Research Coordinator for the Department of Pharmacology and Therapeutics, Primary Investigator
mesh term: Substance Withdrawal Syndrome
mesh term: Acetylcysteine
mesh term: N-monoacetylcystine
sharing ipd: No
ipd description: The results will be published in peer-reviewed journal