<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/NCT03822637</url>
  </required_header>
  <id_info>
    <org_study_id>18-26680</org_study_id>
    <nct_id>NCT03822637</nct_id>
  </id_info>
  <brief_title>The Effect of NAC on Lung Function and CT Mucus Score</brief_title>
  <acronym>ENACT</acronym>
  <official_title>The Effect of NAC on Lung Function and CT Mucus Score</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of California, San Francisco</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</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>
      This study evaluates 20% n-acetylcysteine (NAC) in the treatment of moderate-to-severe asthma&#xD;
      that is complicated by mucus in the airway, as determined by CT imaging. The study is a&#xD;
      crossover design, which means that half the study participants will get 20% NAC in the first&#xD;
      14-day treatment period and placebo in the next 14-day treatment period; and the other half&#xD;
      will get placebo in the first 14-day treatment period and 20% NAC in the next 14-day&#xD;
      treatment period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      N-acetylcystine (NAC) is a mucolytic medication, meaning that it breaks apart mucus.&#xD;
      Investigators know that mucus is a factor in severe asthma attacks. However, mucus may be a&#xD;
      factor in chronic severe asthma as well. This role has been hard to prove because of&#xD;
      difficulty in showing that mucus occludes the lumen in chronic severe disease. Using a novel&#xD;
      approach of scoring mucus occlusion, investigators have used CT imaging to uncover that a&#xD;
      majority of people with severe asthma have at least one lung segment with a mucus plug and&#xD;
      27% have more than four lung segments with mucus plugs.&#xD;
&#xD;
      Historically, studies of mucolytics, like NAC, have not shown benefit in other obstructive&#xD;
      lung diseases, like Chronic Obstructive Pulmonary Disease (COPD). However, utilizing CT mucus&#xD;
      scores as a biomarker, investigators believe that mucolytic treatment may prove useful for&#xD;
      those with significant mucus impaction.&#xD;
&#xD;
      This is a randomized, double-blind, placebo-controlled phase 4 study of 20% NAC in patients&#xD;
      with asthma who also have evidence of mucus in their lungs as determined by CT imaging.&#xD;
      Investigators hypothesize that by treating asthmatics, chosen based on the presence of mucus&#xD;
      in the airways, with a mucolytic like NAC, will result in an improvement of lung function.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 20, 2019</start_date>
  <completion_date type="Anticipated">March 2024</completion_date>
  <primary_completion_date type="Anticipated">March 2024</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in FEV1</measure>
    <time_frame>Through study completion, an average of 9 weeks</time_frame>
    <description>The primary outcome is the % change in FEV1 from the start to the end of each two-week treatment period (either placebo or 20% NAC).</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>20% n-acetylcystine (NAC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>NAC (trade name: Mucomyst) is manufactured by American Regent. The active drug studied here is 20% NAC coadministered with albuterol and delivered via nebulizer three times per day for fourteen days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>0.9% saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Normal saline will be coadministered with albuterol as the placebo agent via a nebulizer three times per day for fourteen days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>n-acetylcystine + albuterol</intervention_name>
    <description>NAC is a mucolytic drug and Albuterol is a bronchodilator.</description>
    <arm_group_label>20% n-acetylcystine (NAC)</arm_group_label>
    <other_name>Mucomyst</other_name>
    <other_name>NAC</other_name>
    <other_name>n-acetylcystine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>0.9% saline + albuterol</intervention_name>
    <description>Normal saline is a placebo agent and Albuterol is a bronchodilator.</description>
    <arm_group_label>0.9% saline</arm_group_label>
    <other_name>Normal saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female between the ages of 18 and 80 years of age at Visit 1&#xD;
&#xD;
          2. Written informed consent obtained from subject and ability for subject to comply with&#xD;
             the requirements of the study.&#xD;
&#xD;
          3. Able to perform reproducible spirometry according to American Thoracic Society (ATS)&#xD;
             criteria&#xD;
&#xD;
          4. Physiological evidence of airflow obstruction (FEV1 bronchodilator reversibility of ≥&#xD;
             12% or hyperreactivity to methacholine reflected by a methacholine provocative&#xD;
             concentration that results in a 20% fall in FEV1(PC20) ≤ 16 mg/mL)&#xD;
&#xD;
          5. Clinical history of asthma per patient report or medical record&#xD;
&#xD;
          6. Pre-bronchodilator FEV1 &gt; 35% predicted&#xD;
&#xD;
          7. Post-bronchodilator FEV1 &gt; 40% but &lt; 90% predicted&#xD;
&#xD;
          8. Asthma requiring treatment with inhaled corticosteroids (ICS) for 3 months or greater&#xD;
&#xD;
          9. CT mucus score ≥ 5&#xD;
&#xD;
         10. Ability to tolerate study drug reflected by a post-treatment FEV1 ≥ 80% of pre-&#xD;
             treatment, pre-bronchodilator FEV1&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant, breastfeeding, or unwilling to practice birth control during participation&#xD;
             in the study&#xD;
&#xD;
          2. Presence of a condition or abnormality that in the opinion of the Investigator would&#xD;
             compromise the safety of the patient or the quality of the data&#xD;
&#xD;
          3. Smoking of tobacco or other recreational inhalants in last year and/or &gt;10 pack-year&#xD;
             smoking history&#xD;
&#xD;
          4. Adherence to study drug ≤ 70% after first treatment period&#xD;
&#xD;
          5. Current participation in an investigational drug trial&#xD;
&#xD;
          6. Other chronic pulmonary disorders, including (but not limited to) cystic fibrosis,&#xD;
             chronic obstructive pulmonary disease, chronic bronchitis, vocal cord dysfunction&#xD;
             (that is the sole cause of respiratory symptoms and at the PI's discretion), severe&#xD;
             scoliosis or chest wall deformities that affect lung function, or congenital disorders&#xD;
             of the lungs or airways&#xD;
&#xD;
          7. Unwillingness to follow study procedures&#xD;
&#xD;
          8. History of allergy or intolerance to study drug&#xD;
&#xD;
          9. Any other criteria that places the subject at unnecessary risk according to the&#xD;
             judgment of the Principal Investigator&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John Fahy, M.D, M.Sc.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Xavier Orain, BS</last_name>
    <phone>415-502-3472</phone>
    <email>xavier.orain@ucsf.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>UCSF Airway Clinical Research Center</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ariana Baum, BA</last_name>
      <phone>415-514-1539</phone>
      <email>ariana.baum@ucsf.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Hays SR, Fahy JV. The role of mucus in fatal asthma. Am J Med. 2003 Jul;115(1):68-9. doi: 10.1016/s0002-9343(03)00260-2. No abstract available.</citation>
    <PMID>12867239</PMID>
  </reference>
  <reference>
    <citation>DUNNILL MS. The pathology of asthma, with special reference to changes in the bronchial mucosa. J Clin Pathol. 1960 Jan;13(1):27-33. doi: 10.1136/jcp.13.1.27.</citation>
    <PMID>13818688</PMID>
  </reference>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>December 14, 2018</study_first_submitted>
  <study_first_submitted_qc>January 28, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <last_update_submitted>February 8, 2023</last_update_submitted>
  <last_update_submitted_qc>February 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 10, 2023</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>Acetylcysteine</mesh_term>
    <mesh_term>Albuterol</mesh_term>
    <mesh_term>N-monoacetylcystine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03822637
org study id: 18-26680
nct id: NCT03822637
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This study evaluates 20% n-acetylcysteine (NAC) in the treatment of moderate-to-severe asthma
      that is complicated by mucus in the airway, as determined by CT imaging. The study is a
      crossover design, which means that half the study participants will get 20% NAC in the first
      14-day treatment period and placebo in the next 14-day treatment period; and the other half
      will get placebo in the first 14-day treatment period and 20% NAC in the next 14-day
      treatment period.
N-acetylcystine (NAC) is a mucolytic medication, meaning that it breaks apart mucus.
      Investigators know that mucus is a factor in severe asthma attacks. However, mucus may be a
      factor in chronic severe asthma as well. This role has been hard to prove because of
      difficulty in showing that mucus occludes the lumen in chronic severe disease. Using a novel
      approach of scoring mucus occlusion, investigators have used CT imaging to uncover that a
      majority of people with severe asthma have at least one lung segment with a mucus plug and
      27% have more than four lung segments with mucus plugs.

      Historically, studies of mucolytics, like NAC, have not shown benefit in other obstructive
      lung diseases, like Chronic Obstructive Pulmonary Disease (COPD). However, utilizing CT mucus
      scores as a biomarker, investigators believe that mucolytic treatment may prove useful for
      those with significant mucus impaction.

      This is a randomized, double-blind, placebo-controlled phase 4 study of 20% NAC in patients
      with asthma who also have evidence of mucus in their lungs as determined by CT imaging.
      Investigators hypothesize that by treating asthmatics, chosen based on the presence of mucus
      in the airways, with a mucolytic like NAC, will result in an improvement of lung function.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Change in FEV1
time frame: Through study completion, an average of 9 weeks
description: The primary outcome is the % change in FEV1 from the start to the end of each two-week treatment period (either placebo or 20% NAC).
arm group label: 20% n-acetylcystine (NAC)
arm group type: Experimental
description: NAC (trade name: Mucomyst) is manufactured by American Regent. The active drug studied here is 20% NAC coadministered with albuterol and delivered via nebulizer three times per day for fourteen days.
arm group label: 0.9% saline
arm group type: Placebo Comparator
description: Normal saline will be coadministered with albuterol as the placebo agent via a nebulizer three times per day for fourteen days.
intervention type: Drug
intervention name: n-acetylcystine + albuterol
description: NAC is a mucolytic drug and Albuterol is a bronchodilator.
arm group label: 20% n-acetylcystine (NAC)
other name: Mucomyst
other name: NAC
other name: n-acetylcystine
intervention type: Drug
intervention name: 0.9% saline + albuterol
description: Normal saline is a placebo agent and Albuterol is a bronchodilator.
arm group label: 0.9% saline
other name: Normal saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: John Fahy, M.D, M.Sc.
role: Principal Investigator
affiliation: University of California, San Francisco
last name: Xavier Orain, BS
phone: 415-502-3472
email: xavier.orain@ucsf.edu
facility: 
status: Recruiting
contact: 
country: United States
citation: Hays SR, Fahy JV. The role of mucus in fatal asthma. Am J Med. 2003 Jul;115(1):68-9. doi: 10.1016/s0002-9343(03)00260-2. No abstract available.
PMID: 12867239
citation: DUNNILL MS. The pathology of asthma, with special reference to changes in the bronchial mucosa. J Clin Pathol. 1960 Jan;13(1):27-33. doi: 10.1136/jcp.13.1.27.
PMID: 13818688
responsible party type: Sponsor
mesh term: Acetylcysteine
mesh term: Albuterol
mesh term: N-monoacetylcystine
sharing ipd: No