<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/NCT02972398</url>
  </required_header>
  <id_info>
    <org_study_id>NAC-2015-TJAH</org_study_id>
    <nct_id>NCT02972398</nct_id>
  </id_info>
  <brief_title>N-Acetyl Cysteine Supplementation in Therapy Refractory Major Depressive Disorders</brief_title>
  <official_title>N-Acetyl Cysteine add-on to Antidepressant Medication in Therapy Refractory Major Depressive Disorder Patients With Increased Inflammatory Activity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tianjin Anding Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tianjin Anding Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is to evaluate the efficacy of N-acetylcysteine (NAC) add-on to&#xD;
      antidepressant medication in treating patients who do not relieve during standard&#xD;
      antidepressant treatment for 6 weeks at least. Meanwhile, secondary outcomes will include&#xD;
      changes in some biomarkers and on specifically local brain activity (functional Magnetic&#xD;
      Resonance Imaging, fMRI) and white matter integrity (Diffusion Tensor Imaging, DTI). The&#xD;
      hypothesis of this study is that NAC has positive effects on refractory major depressive&#xD;
      disorder patients with increased inflammatory activity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      It's a double-blind randomised placebo controlled antidepressant augmentation study with&#xD;
      12-week treatment and 8-week follow up. Its purpose is to investigate antidepressant efficacy&#xD;
      and safety of NAC in patients with treatment resistant depression (TRD) defined as&#xD;
      insufficient response to 1 or more antidepressants given for at least 6 weeks and in an&#xD;
      adequate dose, displaying increased peripheral inflammatory activity and moderate to severe&#xD;
      depression. Apart from studying the effects of NAC on depression severity, the secondary&#xD;
      outcomes are to examine a range of biomarkers related to potentially important underlying&#xD;
      mechanisms such as oxidative stress and inflammatory activity and to evaluate the effects on&#xD;
      brain functioning (fMRI) and on white matter integrity (DTI). Scale assessments are performed&#xD;
      in the week preceding initiation of treatment, during the treatment period, at the end of the&#xD;
      treatment period and at 8-week follow up. Neuro-imaging is performed before the treatment&#xD;
      starts and in week 12, before the study medication is terminated. Collection of blood and&#xD;
      morning urine only takes place at three time points, in the week preceding initiation of&#xD;
      treatment, closely before tapering off the study medication and at the end of 8-week follow&#xD;
      up. This study is hoped to show that NAC perform positive effects on those aspects mentioned&#xD;
      above.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 2015</start_date>
  <completion_date type="Anticipated">September 2023</completion_date>
  <primary_completion_date type="Anticipated">July 2023</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The change from baseline Hamilton Depression Rating Scale (HAMD)-17 items at week2,4,6,8,10,and 12.</measure>
    <time_frame>baseline, Week 2,4,6,8,10, and 12</time_frame>
    <description>The main objective is to investigate whether daily oral NAC administration in addition to regular treatment with an antidepressant will alleviate the severity of MDD symptoms as measured with the HAMD-17 after 12 weeks of treatment compared to placebo addition, and we also look at other time points, such as week 2,4,6,8,and 10.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The change from baseline HAMD-17 items at week14,16,18,and 20.</measure>
    <time_frame>baseline, Week 14,16,18,and 20.</time_frame>
    <description>We also look at whether daily oral NAC treatment will still have measurable effects on HAMD-17 score at 8 weeks follow-up after discontinuation of NAC treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The effects of augmentation treatment with NAC on scores in Beck Anxiety Inventory (BAI)</measure>
    <time_frame>baseline, Week 4,8,12,16,and 20.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The effects of augmentation treatment with NAC on scores in Inventory of Depressive Symptoms-Self-Rated (IDS-SR)</measure>
    <time_frame>baseline, Week 4,8,12,16,and 20.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The effects of augmentation treatment with NAC on scores in WHO Disability Assessment Schedule Ⅱ (WHODAS-Ⅱ)</measure>
    <time_frame>baseline, Week 4,8,12,16,and 20.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The effects of augmentation treatment with NAC on scores in Montreal Cognitive Assessment (MoCA)</measure>
    <time_frame>baseline, Week 4,8,12,16,and 20.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The effects of augmentation treatment with NAC on local brain activity (fMRI and DTI)</measure>
    <time_frame>baseline, the end of week 12.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The effects of augmentation treatment with NAC on a range of biomarkers representing the alleged underlying pathophysiological mechanisms</measure>
    <time_frame>baseline, the end of the week 12 and 20</time_frame>
    <description>biomarkers associated with inflammation, oxidative stress, and neurogenesis in sample of serum and urine.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessments the side effects measured with Checklist of 52 Somatic Items (CSI)</measure>
    <time_frame>baseline, Week 4,8,12,16,and 20.</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Major Depressive Disorders</condition>
  <arm_group>
    <arm_group_label>NAC group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants of &quot;NAC group&quot; receive 1000 mg NAC twice daily for 12 weeks as add-on to either a selective serotonin reuptake inhibitor (SSRI) or a serotonin and noradrenalin reuptake inhibitor (SNRI)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants of &quot;Placebo group&quot; receive placebo matched with NAC twice daily for 12 weeks as add-on to either a selective serotonin reuptake inhibitor (SSRI) or a serotonin and noradrenalin reuptake inhibitor (SNRI)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>N-acetylcysteine</intervention_name>
    <description>Participants of interventional group receive 1000mg N-acetylcysteine twice daily for 12 weeks.</description>
    <arm_group_label>NAC group</arm_group_label>
    <other_name>YiWeiShi</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo comparator of N-acetylcysteine</intervention_name>
    <description>Participants of placebo group receive placebo comparator matching with N-acetylcysteine twice daily for 12 weeks.</description>
    <arm_group_label>Placebo group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  a current episode of MDD diagnosed according to Diagnostic and Statistical Manual of&#xD;
             Mental Disorders, Fourth Edition (DSM-IV-TR) diagnosed with SCID&#xD;
&#xD;
          -  an age between 18 and 65 years&#xD;
&#xD;
          -  a total score of HAMD-17 ≥ 17&#xD;
&#xD;
          -  a CRP level between 0.85 and 10 mg/L (The CRP range is based on literature values for&#xD;
             mild to moderate chronic inflammation, while values &gt; 10 mg/L point at acute&#xD;
             inflammation. A pilot study at the Tianjin Hospital (n=62) indicated that&#xD;
             approximately one third of all patients with MDD will have CRP values within this&#xD;
             range). insufficient response to 1 or more antidepressants given for at least 6 weeks&#xD;
             and in an adequate dose during the current episode&#xD;
&#xD;
          -  stable dose of the current antidepressant drug for at least 2 weeks prior to&#xD;
             initiation of the study&#xD;
&#xD;
          -  Patients are allowed to use benzodiazepines (BZD) to relieve anxiety during the first&#xD;
             phase of antidepressant treatment (Anding Hospital protocol). Benzodiazepines may also&#xD;
             be prescribed because of sleeping problems during the trial. BZD use will be recorded&#xD;
             at all assessments during the trial and after follow-up.&#xD;
&#xD;
          -  Patients are compliant with treatment according to the judgement of the treating&#xD;
             clinician.&#xD;
&#xD;
          -  Female subjects will be eligible to participate in the study if they are of&#xD;
             non-childbearing potential or of child-bearing potential and willing to practice&#xD;
             appropriate birth control methods during the study. Clinical patients always get a&#xD;
             pregnancy test before start of treatment.&#xD;
&#xD;
          -  Participant or guardian has to sign informed consent. The patients' guardians will&#xD;
             sign the informed consent on behalf of the participants when the capacity of&#xD;
             participants to consent is compromised.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A history of manic episode&#xD;
&#xD;
          -  Use of mood stabilizer&#xD;
&#xD;
          -  Use of antipsychotic medication with more than half of the maximum dosage suggested in&#xD;
             the instruction&#xD;
&#xD;
          -  History of substance abuse or dependence&#xD;
&#xD;
          -  An allergic reaction to NAC or any component of the preparation&#xD;
&#xD;
          -  Severe somatic diseases that might interfere with regular antidepressant treatment&#xD;
             including conditions such as kidney and liver failure, uncontrolled hypertension,&#xD;
             cardiovascular, cerebrovascular and pulmonary disease, thyroid disease, diabetes,&#xD;
             epilepsy and asthma.&#xD;
&#xD;
          -  Use of anti-inflammatory medication for longer than 7 days in the last two months&#xD;
             preceding the trial&#xD;
&#xD;
          -  Use of immunosuppressive medication such as oral steroid hormones&#xD;
&#xD;
          -  History of chronic infection, such as Tuberculosis, AIDS, hepatitis&#xD;
&#xD;
          -  CRP value &gt; 10 mg/L&#xD;
&#xD;
          -  Women in pregnancy or lactation period&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Chenghao Yang, Master</last_name>
    <phone>086 13752539531</phone>
    <email>yts83420@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Tianjin Anding Hospital</name>
      <address>
        <city>Tianjin</city>
        <state>Tianjin</state>
        <zip>300222</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jie Li, Doctor</last_name>
      <phone>+86 022 88188006</phone>
      <email>tjlijie3827@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>November 12, 2016</study_first_submitted>
  <study_first_submitted_qc>November 20, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 23, 2016</study_first_posted>
  <last_update_submitted>September 21, 2022</last_update_submitted>
  <last_update_submitted_qc>September 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 22, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>treatment resistant depression</keyword>
  <keyword>N-Acetyl Cysteine</keyword>
  <keyword>inflammation mediators</keyword>
  <keyword>oxidative stress</keyword>
  <keyword>brain imaging</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder, Major</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>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/NCT02972398
org study id: NAC-2015-TJAH
nct id: NCT02972398
lead sponsor: 
has dmc: Yes
The aim of this study is to evaluate the efficacy of N-acetylcysteine (NAC) add-on to
      antidepressant medication in treating patients who do not relieve during standard
      antidepressant treatment for 6 weeks at least. Meanwhile, secondary outcomes will include
      changes in some biomarkers and on specifically local brain activity (functional Magnetic
      Resonance Imaging, fMRI) and white matter integrity (Diffusion Tensor Imaging, DTI). The
      hypothesis of this study is that NAC has positive effects on refractory major depressive
      disorder patients with increased inflammatory activity.
It's a double-blind randomised placebo controlled antidepressant augmentation study with
      12-week treatment and 8-week follow up. Its purpose is to investigate antidepressant efficacy
      and safety of NAC in patients with treatment resistant depression (TRD) defined as
      insufficient response to 1 or more antidepressants given for at least 6 weeks and in an
      adequate dose, displaying increased peripheral inflammatory activity and moderate to severe
      depression. Apart from studying the effects of NAC on depression severity, the secondary
      outcomes are to examine a range of biomarkers related to potentially important underlying
      mechanisms such as oxidative stress and inflammatory activity and to evaluate the effects on
      brain functioning (fMRI) and on white matter integrity (DTI). Scale assessments are performed
      in the week preceding initiation of treatment, during the treatment period, at the end of the
      treatment period and at 8-week follow up. Neuro-imaging is performed before the treatment
      starts and in week 12, before the study medication is terminated. Collection of blood and
      morning urine only takes place at three time points, in the week preceding initiation of
      treatment, closely before tapering off the study medication and at the end of 8-week follow
      up. This study is hoped to show that NAC perform positive effects on those aspects mentioned
      above.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: The change from baseline Hamilton Depression Rating Scale (HAMD)-17 items at week2,4,6,8,10,and 12.
time frame: baseline, Week 2,4,6,8,10, and 12
description: The main objective is to investigate whether daily oral NAC administration in addition to regular treatment with an antidepressant will alleviate the severity of MDD symptoms as measured with the HAMD-17 after 12 weeks of treatment compared to placebo addition, and we also look at other time points, such as week 2,4,6,8,and 10.
measure: The change from baseline HAMD-17 items at week14,16,18,and 20.
time frame: baseline, Week 14,16,18,and 20.
description: We also look at whether daily oral NAC treatment will still have measurable effects on HAMD-17 score at 8 weeks follow-up after discontinuation of NAC treatment.
measure: The effects of augmentation treatment with NAC on scores in Beck Anxiety Inventory (BAI)
time frame: baseline, Week 4,8,12,16,and 20.
measure: The effects of augmentation treatment with NAC on scores in Inventory of Depressive Symptoms-Self-Rated (IDS-SR)
time frame: baseline, Week 4,8,12,16,and 20.
measure: The effects of augmentation treatment with NAC on scores in WHO Disability Assessment Schedule Ⅱ (WHODAS-Ⅱ)
time frame: baseline, Week 4,8,12,16,and 20.
measure: The effects of augmentation treatment with NAC on scores in Montreal Cognitive Assessment (MoCA)
time frame: baseline, Week 4,8,12,16,and 20.
measure: The effects of augmentation treatment with NAC on local brain activity (fMRI and DTI)
time frame: baseline, the end of week 12.
measure: The effects of augmentation treatment with NAC on a range of biomarkers representing the alleged underlying pathophysiological mechanisms
time frame: baseline, the end of the week 12 and 20
description: biomarkers associated with inflammation, oxidative stress, and neurogenesis in sample of serum and urine.
measure: Assessments the side effects measured with Checklist of 52 Somatic Items (CSI)
time frame: baseline, Week 4,8,12,16,and 20.
arm group label: NAC group
arm group type: Experimental
description: Participants of "NAC group" receive 1000 mg NAC twice daily for 12 weeks as add-on to either a selective serotonin reuptake inhibitor (SSRI) or a serotonin and noradrenalin reuptake inhibitor (SNRI)
arm group label: Placebo group
arm group type: Placebo Comparator
description: Participants of "Placebo group" receive placebo matched with NAC twice daily for 12 weeks as add-on to either a selective serotonin reuptake inhibitor (SSRI) or a serotonin and noradrenalin reuptake inhibitor (SNRI)
intervention type: Drug
intervention name: N-acetylcysteine
description: Participants of interventional group receive 1000mg N-acetylcysteine twice daily for 12 weeks.
arm group label: NAC group
other name: YiWeiShi
intervention type: Drug
intervention name: placebo comparator of N-acetylcysteine
description: Participants of placebo group receive placebo comparator matching with N-acetylcysteine twice daily for 12 weeks.
arm group label: Placebo group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Chenghao Yang, Master
phone: 086 13752539531
email: yts83420@163.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Depressive Disorder
mesh term: Depression
mesh term: Depressive Disorder, Major
mesh term: Acetylcysteine
mesh term: N-monoacetylcystine
sharing ipd: Undecided