<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/NCT02206178</url>
  </required_header>
  <id_info>
    <org_study_id>CHU-0202</org_study_id>
    <secondary_id>2013-000668-27</secondary_id>
    <nct_id>NCT02206178</nct_id>
  </id_info>
  <brief_title>Acetaminophen's Antinociceptive Effect When Associated With N-Acetylcysteneine</brief_title>
  <acronym>PANACE</acronym>
  <official_title>ACETAMINOPHEN ANTINOCICEPTIVE EFFECT WHEN ASSOCIATED WITH N-ACETYLCYSTENEINE</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Clermont-Ferrand</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Clermont-Ferrand</source>
  <brief_summary>
    <textblock>
      Acetaminophen is one of the most widely used analgesic in the world, recommended for the&#xD;
      symptomatic treatment of fever and pain.&#xD;
&#xD;
      The purpose of this study is to assess the effectiveness of acetaminophen in association with&#xD;
      N-acetylcysteine.&#xD;
&#xD;
      The objective of this study is to evaluate if the association in healthy volunteers of&#xD;
      acetaminophen and N-acétylcystéine&#xD;
&#xD;
        1. - decrease the antinociceptive effect of acetaminophen in comparison to a group control&#xD;
&#xD;
        2. - and if this antinociceptive effect may depend of the genetic polymorphism of GSH&#xD;
           enzyme.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Period 1 : To Day -4 to Day 0&#xD;
&#xD;
      Day -4 at 8:00 am at Clinical Pharmacology Center&#xD;
&#xD;
        -  Inclusion Visit, signature of Informed consent form, clinical exam.&#xD;
&#xD;
        -  Training test&#xD;
&#xD;
        -  Blood sample (GSH, pharmacogenetic, Biochemistry assay)&#xD;
&#xD;
        -  Randomization and attribution of treatment for the fisrt study period at home: (day -4,&#xD;
           -3, -2, -1) 4 days of oral acetaminophen and [N-acetylcysteine or placebo] according to&#xD;
           the randomization plan.&#xD;
&#xD;
      At day -3, -2 and -1 a salivary sample will be done to control the treatment compliance.&#xD;
&#xD;
      Day 0 at Clinical Pharmacology Center Clinical examination Measurement of the basal pain&#xD;
      thresholds and pain evaluation (Visual Analog Scales) Blood and urinary sample (acetaminophen&#xD;
      and GSH assay)&#xD;
&#xD;
      T0 : Administration of product: acetaminophen and [N-acetylcysteine or placebo]&#xD;
&#xD;
      T0+1H: Thermal stimulation according to the established paradigm (threshold temperature +3°C&#xD;
      ) and pain evaluation (Visual Analog Scales)&#xD;
&#xD;
      T0+2H: Thermal stimulation according to the established paradigm (threshold temperature +3°C&#xD;
      ) and pain evaluation (Visual Analog Scales) and Blood sample (acetaminophen assay)&#xD;
&#xD;
      T0+3H: Thermal stimulation according to the established paradigm (threshold temperature +3°C&#xD;
      ) and pain evaluation (Visual Analog Scales)&#xD;
&#xD;
      T0+4H: Thermal stimulation according to the established paradigm (threshold temperature +3°C&#xD;
      ) and pain evaluation (Visual Analog Scales) and Blood and urinary sample (acetaminophen,&#xD;
      GSH, biochemistry assay)&#xD;
&#xD;
      - Lunch before departure&#xD;
&#xD;
      2 weeks of wash-out&#xD;
&#xD;
      Period 2 : To Day 17 to Day 21&#xD;
&#xD;
      Same of period 1. Subject who receives N-acétylcystéine in period 1 will receive placebo in&#xD;
      second period and vice versa.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2013</start_date>
  <completion_date type="Actual">January 2014</completion_date>
  <primary_completion_date type="Actual">January 2014</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pain intensity using Visual Analog Scales (VAS) succeeding thermic stimulations at the threshold temperature +3°C before (T0-1h) and after acetaminophen's administration</measure>
    <time_frame>At day 0</time_frame>
    <description>Pain intensity using Visual Analog Scales (VAS) succeeding thermic stimulations at the threshold temperature +3°C before (T0-1h) and after acetaminophen's administration (T0+1h, T0+2h, T0+3h, T0+4h).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Blood glutathione GSH concentration</measure>
    <time_frame>At day 0</time_frame>
    <description>Blood glutathione GSH concentration at J0 T0-1h and J0 T0+4h</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood of acetaminophen concentration and its metabolites</measure>
    <time_frame>at day 0</time_frame>
    <description>Blood of acetaminophen concentration and its metabolites at J0 T0-1h, T0+2h, and T0+4h.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urinary assay of the rate of acetaminophen and its metabolites</measure>
    <time_frame>at day 0</time_frame>
    <description>Urinary assay of the rate of acetaminophen and its metabolites at J0 T0-1h, and T0+4h.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacogenetic dosage of enzymes involved in glutathione metabolism</measure>
    <time_frame>at day 4</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>acetaminophen</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The purpose of this study is to assess the effectiveness of acetaminophen in association with N-acetylcysteine.&#xD;
The objective of this study is to evaluate if the association in healthy volunteers of acetaminophen and N-acétylcystéine&#xD;
- decrease the antinociceptive effect of acetaminophen in comparison to a group control&#xD;
- and if this antinociceptive effect may depend of the genetic polymorphism of GSH enzyme</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>- decrease the antinociceptive effect of acetaminophen in comparison to a group control&#xD;
- and if this antinociceptive effect may depend of the genetic polymorphism of GSH enzyme</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>N-acetylcysteine combination with acetaminophen</intervention_name>
    <arm_group_label>acetaminophen</arm_group_label>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male&#xD;
&#xD;
          -  Between 18 and 45 years old&#xD;
&#xD;
          -  Without treatment during the 7 days before inclusion specially no use of antalgic and&#xD;
             anti-inflammatory&#xD;
&#xD;
          -  Cooperation and understanding enough to conform to the study obligations -Having given&#xD;
             free, informed written consent&#xD;
&#xD;
          -  Affiliated at system of French social security&#xD;
&#xD;
          -  Inscription or acceptation of inscription in the national register of volunteers&#xD;
             involved in trials.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient with one or many contraindication for the administration of the trial's&#xD;
             products,&#xD;
&#xD;
          -  Patient that have taken N-acetylcysteine as bronchial thinner during the last 3 days,&#xD;
&#xD;
          -  Patient with medical or surgical history judged by the investigator or his&#xD;
             representative as being not compatible with the clinical trial&#xD;
&#xD;
          -  Patient with disease progression during inclusion,&#xD;
&#xD;
          -  Patient with excessive consumption of alcohol, tobacco (+ than 10 cigarette/day),&#xD;
             coffee, tea or drinks with caffeine (equivalent to more than 4 cup a day) or any&#xD;
             addiction to drugs,&#xD;
&#xD;
          -  Patient with a heat pain mean threshold during training higher or equal to 46.5°C,&#xD;
&#xD;
          -  Patient who participated in another clinical trial, located in exclusion period or&#xD;
             received benefits &gt; 4500 euros during 12 months before the beginning of trial,&#xD;
&#xD;
          -  Patient with cooperation and understanding that do not allow him to follow the trial,&#xD;
&#xD;
          -  Patients with minor or under guardianship,&#xD;
&#xD;
          -  No affiliation at system of French social security&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gisèle PICKERING</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Clermont-Ferrand</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU de Clermont-Ferrand</name>
      <address>
        <city>Clermont-Ferrand</city>
        <zip>63003</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>July 2016</verification_date>
  <study_first_submitted>July 29, 2014</study_first_submitted>
  <study_first_submitted_qc>July 31, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 1, 2014</study_first_posted>
  <last_update_submitted>July 28, 2016</last_update_submitted>
  <last_update_submitted_qc>July 28, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 29, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetaminophen</mesh_term>
    <mesh_term>Acetylcysteine</mesh_term>
    <mesh_term>N-monoacetylcystine</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02206178
org study id: CHU-0202
secondary id: 2013-000668-27
nct id: NCT02206178
lead sponsor: 
Acetaminophen is one of the most widely used analgesic in the world, recommended for the
      symptomatic treatment of fever and pain.

      The purpose of this study is to assess the effectiveness of acetaminophen in association with
      N-acetylcysteine.

      The objective of this study is to evaluate if the association in healthy volunteers of
      acetaminophen and N-acétylcystéine

        1. - decrease the antinociceptive effect of acetaminophen in comparison to a group control

        2. - and if this antinociceptive effect may depend of the genetic polymorphism of GSH
           enzyme.
Period 1 : To Day -4 to Day 0

      Day -4 at 8:00 am at Clinical Pharmacology Center

        -  Inclusion Visit, signature of Informed consent form, clinical exam.

        -  Training test

        -  Blood sample (GSH, pharmacogenetic, Biochemistry assay)

        -  Randomization and attribution of treatment for the fisrt study period at home: (day -4,
           -3, -2, -1) 4 days of oral acetaminophen and [N-acetylcysteine or placebo] according to
           the randomization plan.

      At day -3, -2 and -1 a salivary sample will be done to control the treatment compliance.

      Day 0 at Clinical Pharmacology Center Clinical examination Measurement of the basal pain
      thresholds and pain evaluation (Visual Analog Scales) Blood and urinary sample (acetaminophen
      and GSH assay)

      T0 : Administration of product: acetaminophen and [N-acetylcysteine or placebo]

      T0+1H: Thermal stimulation according to the established paradigm (threshold temperature +3°C
      ) and pain evaluation (Visual Analog Scales)

      T0+2H: Thermal stimulation according to the established paradigm (threshold temperature +3°C
      ) and pain evaluation (Visual Analog Scales) and Blood sample (acetaminophen assay)

      T0+3H: Thermal stimulation according to the established paradigm (threshold temperature +3°C
      ) and pain evaluation (Visual Analog Scales)

      T0+4H: Thermal stimulation according to the established paradigm (threshold temperature +3°C
      ) and pain evaluation (Visual Analog Scales) and Blood and urinary sample (acetaminophen,
      GSH, biochemistry assay)

      - Lunch before departure

      2 weeks of wash-out

      Period 2 : To Day 17 to Day 21

      Same of period 1. Subject who receives N-acétylcystéine in period 1 will receive placebo in
      second period and vice versa.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Pain intensity using Visual Analog Scales (VAS) succeeding thermic stimulations at the threshold temperature +3°C before (T0-1h) and after acetaminophen's administration
time frame: At day 0
description: Pain intensity using Visual Analog Scales (VAS) succeeding thermic stimulations at the threshold temperature +3°C before (T0-1h) and after acetaminophen's administration (T0+1h, T0+2h, T0+3h, T0+4h).
measure: Blood glutathione GSH concentration
time frame: At day 0
description: Blood glutathione GSH concentration at J0 T0-1h and J0 T0+4h
measure: Blood of acetaminophen concentration and its metabolites
time frame: at day 0
description: Blood of acetaminophen concentration and its metabolites at J0 T0-1h, T0+2h, and T0+4h.
measure: Urinary assay of the rate of acetaminophen and its metabolites
time frame: at day 0
description: Urinary assay of the rate of acetaminophen and its metabolites at J0 T0-1h, and T0+4h.
measure: Pharmacogenetic dosage of enzymes involved in glutathione metabolism
time frame: at day 4
arm group label: acetaminophen
arm group type: Experimental
description: The purpose of this study is to assess the effectiveness of acetaminophen in association with N-acetylcysteine.
The objective of this study is to evaluate if the association in healthy volunteers of acetaminophen and N-acétylcystéine
- decrease the antinociceptive effect of acetaminophen in comparison to a group control
- and if this antinociceptive effect may depend of the genetic polymorphism of GSH enzyme
arm group label: placebo
arm group type: Placebo Comparator
description: - decrease the antinociceptive effect of acetaminophen in comparison to a group control
- and if this antinociceptive effect may depend of the genetic polymorphism of GSH enzyme
intervention type: Drug
intervention name: N-acetylcysteine combination with acetaminophen
arm group label: acetaminophen
arm group label: placebo
intervention type: Drug
intervention name: Placebo
arm group label: placebo
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Gisèle PICKERING
role: Principal Investigator
affiliation: University Hospital, Clermont-Ferrand
facility: 
country: France
responsible party type: Sponsor
mesh term: Acetaminophen
mesh term: Acetylcysteine
mesh term: N-monoacetylcystine