<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/NCT03768557</url>
  </required_header>
  <id_info>
    <org_study_id>R50651/RE001</org_study_id>
    <nct_id>NCT03768557</nct_id>
  </id_info>
  <brief_title>The Effect of Acute Minocycline Administration on Emotional Processing and Cognition in Healthy Volunteers</brief_title>
  <official_title>The Effect of Acute Minocycline Administration on Emotional Processing and Cognition in Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Oxford</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Oxford</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>
      There is growing interest in the possibility of producing more effective antidepressant&#xD;
      treatments that target a wider range of pathways involved in depression, including&#xD;
      anti-inflammatory and anti-glutamatergic systems. Minocycline is a novel pharmacological&#xD;
      agent; in addition to its antibiotic and anti-inflammatory properties, it also acts in the&#xD;
      brain as an anti-glutamatergic and anti-oxidant agent. Since both excessive glutamate and&#xD;
      oxidative stress are implicated in major depression, and appear to be connected to&#xD;
      pro-inflammatory activity, this drug offers a unique tool with which the investigators can&#xD;
      measure the effects of targeting these pathways on emotional processing. Participants will&#xD;
      receive a single dose of either the drug (200 mg minocycline) or placebo, and will then&#xD;
      undergo a well-validated computerised battery of emotional processing tasks that have&#xD;
      previously been shown to be sensitive to standard antidepressant drugs. Tasks include&#xD;
      presentation of positive and negative emotional words or pictures, to which participants'&#xD;
      responses are measured. These tasks have been widely used previously without any adverse&#xD;
      effects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Current antidepressant treatments, which largely target monoamine pathways, are efficacious&#xD;
      in treating many aspects of major depression, however it is estimated that more than 30% of&#xD;
      depressed patients fail to respond to standard antidepressant medications. Thus, there is a&#xD;
      strong clinical need to identify and investigate novel treatment strategies that target&#xD;
      different pathways involved in the pathophysiology of mood disorders. Mounting evidence&#xD;
      indicates a potentially important role of inflammation in major depression; both clinical and&#xD;
      animal studies have shown that pro-inflammatory cytokines can induce a behavioural repertoire&#xD;
      of symptoms collectively referred to as 'sickness behaviours,' which include cognitive and&#xD;
      mood symptoms, such as depression, anxiety, memory impairment, fatigue and anhedonia.&#xD;
      Furthermore, elevated levels of peripheral pro-inflammatory cytokines, such as tumour&#xD;
      necrosis factor (TNF)-α and interleukin (IL)-6, have been consistently reported in clinical&#xD;
      mood disorders, including major depression. Evidence also points to the ability of&#xD;
      pro-inflammatory cytokines to cause excitotoxicity (due to increased release of glutamate)&#xD;
      and oxidative stress that are strongly implicated in the pathophysiology of major depression.&#xD;
      Such evidence has therefore led to growing interest in testing effects of anti-inflammatory&#xD;
      treatments on mood and emotional function to investigate whether the inflammatory-mood&#xD;
      pathway could represent a novel drug target for new antidepressant therapies.&#xD;
&#xD;
      Minocycline has been selected for use in the present study as it is a pharmacologically&#xD;
      interesting agent with an unusual combination of anti-inflammatory activity, in addition to&#xD;
      anti-glutamatergic, anti-oxidant and neuro-protective actions. Thus, owing to its central&#xD;
      action on systems that are thought to be involved in major depression, minocycline provides&#xD;
      an interesting tool to investigate effects on cognition and emotional processing,&#xD;
      particularly negative affective biases.&#xD;
&#xD;
      Negative affective biases in emotional processing are highly relevant to clinical mood&#xD;
      disorders and they are well-recognised in the aetiology and maintenance of depression, such&#xD;
      that depressed individuals are more likely to interpret, focus on and remember negative&#xD;
      compared to positive emotional cues in self-relevant neuropsychological tasks. Antidepressant&#xD;
      treatments have been shown to cause early, subconscious positive changes in emotional&#xD;
      processing biases, which are evident in computerised tasks after one single dose of&#xD;
      antidepressant. Recent theory suggests that over time this positive change in emotional bias&#xD;
      contributes to improved mood.&#xD;
&#xD;
      Since elevated inflammatory markers appear to negatively affect mood and neuropsychological&#xD;
      function, the investigators believe there is a need to expand our understanding of the&#xD;
      psychological effects of reducing inflammatory markers. To do so, subjects will be&#xD;
      administered either a single dose of 200 mg minocycline or placebo, after which they will&#xD;
      complete a well-validated computerized battery of psychological tasks, which includes&#xD;
      paradigms such as facial expression recognition, emotional categorization and emotional&#xD;
      memory tasks that have previously been shown to be sensitive to conventional antidepressant&#xD;
      treatments in healthy volunteers.&#xD;
&#xD;
      The results of this study will be compared to effects of common antidepressant treatments&#xD;
      found using this same model within the investigators' lab and others. If effects are found to&#xD;
      be comparable, this could not only provide further support for the emotional processing&#xD;
      theory of antidepressant action, but it could also help to identify novel therapeutic targets&#xD;
      for new treatments that could benefit depressed patients who do not respond successfully to&#xD;
      current antidepressants.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 26, 2017</start_date>
  <completion_date type="Actual">October 25, 2018</completion_date>
  <primary_completion_date type="Actual">October 25, 2018</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Facial Expression Recognition Task</measure>
    <time_frame>2 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Emotional Categorization Task</measure>
    <time_frame>2 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Emotional Recall Task</measure>
    <time_frame>2 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Emotional Recognition Memory Task</measure>
    <time_frame>2 hours</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Attentional Dot-Probe</measure>
    <time_frame>2 hours</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>N-back Task</measure>
    <time_frame>2 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Contextual Cueing Task</measure>
    <time_frame>2 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Priming Task</measure>
    <time_frame>2 hours</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Concentration of the inflammatory marker TNF-alpha in serum Serum inflammatory cytokines and metabolites</measure>
    <time_frame>0 and 4 hours</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Concentration of the inflammatory marker IL-6 in serum</measure>
    <time_frame>0 and 4 hours</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Concentration of the inflammatory marker C-reactive protein in serum</measure>
    <time_frame>0 and 4 hours</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Concentration of the stress hormone cortisol in serum</measure>
    <time_frame>0 and 4hours</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Concentration of metabolites (amino acids and lipids) in serum</measure>
    <time_frame>0 and 4 hours</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Mood</condition>
  <condition>Cognitive Change</condition>
  <arm_group>
    <arm_group_label>Minocycline</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>single dose of minocycline (200mg)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>lactose pills (400mg)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Minocycline</intervention_name>
    <description>Minocycline (200mg)</description>
    <arm_group_label>Minocycline</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>Lactose (400mg)</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants are willing and able to give informed consent for participation in the&#xD;
             study&#xD;
&#xD;
          -  Male or female, aged between 18 and 55&#xD;
&#xD;
          -  Body mass index (BMI) within the range of 19 - 30 kg/m2&#xD;
&#xD;
          -  Sufficiently fluent in English to understand the tasks and instructions&#xD;
&#xD;
          -  Female subjects must be outside of their pre-menstrual week on the testing day&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current or past history of any psychiatric disorder (e.g. depression, anxiety)&#xD;
&#xD;
          -  Any medical contra-indication (for example hepatic impairment)&#xD;
&#xD;
          -  Current use of any medication which, in the opinion of the study physician, will&#xD;
             interfere with minocycline or cause any contraindications&#xD;
&#xD;
          -  Known hypersensitivity to tetracyclines or to any of the excipients in minocycline&#xD;
             capsules&#xD;
&#xD;
          -  Steroidal or non-steroidal anti-inflammatory medication within preceding 2 weeks,&#xD;
             including aspirin and ibuprofen&#xD;
&#xD;
          -  Congenital or acquired immune deficiency (including participants receiving&#xD;
             immunosuppressive or antimitotic drugs)&#xD;
&#xD;
          -  Current pregnancy or breastfeeding&#xD;
&#xD;
          -  Current substance misuse&#xD;
&#xD;
          -  Recent (&lt; 3 months) use of psychotropic drugs&#xD;
&#xD;
          -  Participant in a psychological or medical study involving the use of medication within&#xD;
             the last 3 months&#xD;
&#xD;
          -  Participant in another study using the same / a similar battery of cognitive /&#xD;
             emotional tasks in the last 3 months&#xD;
&#xD;
          -  Current smoker of more than 5 cigarettes per day&#xD;
&#xD;
          -  Dyslexia (given the nature of the computer tasks)&#xD;
&#xD;
          -  Lactose intolerance (placebo is composed of lactose capsules)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Warneford Hospital</name>
      <address>
        <city>Oxford</city>
        <state>Oxfordshire</state>
        <zip>OX3 7JX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>November 22, 2018</study_first_submitted>
  <study_first_submitted_qc>December 6, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 7, 2018</study_first_posted>
  <last_update_submitted>April 16, 2019</last_update_submitted>
  <last_update_submitted_qc>April 16, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 18, 2019</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>Minocycline</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/NCT03768557
org study id: R50651/RE001
nct id: NCT03768557
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
There is growing interest in the possibility of producing more effective antidepressant
      treatments that target a wider range of pathways involved in depression, including
      anti-inflammatory and anti-glutamatergic systems. Minocycline is a novel pharmacological
      agent; in addition to its antibiotic and anti-inflammatory properties, it also acts in the
      brain as an anti-glutamatergic and anti-oxidant agent. Since both excessive glutamate and
      oxidative stress are implicated in major depression, and appear to be connected to
      pro-inflammatory activity, this drug offers a unique tool with which the investigators can
      measure the effects of targeting these pathways on emotional processing. Participants will
      receive a single dose of either the drug (200 mg minocycline) or placebo, and will then
      undergo a well-validated computerised battery of emotional processing tasks that have
      previously been shown to be sensitive to standard antidepressant drugs. Tasks include
      presentation of positive and negative emotional words or pictures, to which participants'
      responses are measured. These tasks have been widely used previously without any adverse
      effects.
Current antidepressant treatments, which largely target monoamine pathways, are efficacious
      in treating many aspects of major depression, however it is estimated that more than 30% of
      depressed patients fail to respond to standard antidepressant medications. Thus, there is a
      strong clinical need to identify and investigate novel treatment strategies that target
      different pathways involved in the pathophysiology of mood disorders. Mounting evidence
      indicates a potentially important role of inflammation in major depression; both clinical and
      animal studies have shown that pro-inflammatory cytokines can induce a behavioural repertoire
      of symptoms collectively referred to as 'sickness behaviours,' which include cognitive and
      mood symptoms, such as depression, anxiety, memory impairment, fatigue and anhedonia.
      Furthermore, elevated levels of peripheral pro-inflammatory cytokines, such as tumour
      necrosis factor (TNF)-α and interleukin (IL)-6, have been consistently reported in clinical
      mood disorders, including major depression. Evidence also points to the ability of
      pro-inflammatory cytokines to cause excitotoxicity (due to increased release of glutamate)
      and oxidative stress that are strongly implicated in the pathophysiology of major depression.
      Such evidence has therefore led to growing interest in testing effects of anti-inflammatory
      treatments on mood and emotional function to investigate whether the inflammatory-mood
      pathway could represent a novel drug target for new antidepressant therapies.

      Minocycline has been selected for use in the present study as it is a pharmacologically
      interesting agent with an unusual combination of anti-inflammatory activity, in addition to
      anti-glutamatergic, anti-oxidant and neuro-protective actions. Thus, owing to its central
      action on systems that are thought to be involved in major depression, minocycline provides
      an interesting tool to investigate effects on cognition and emotional processing,
      particularly negative affective biases.

      Negative affective biases in emotional processing are highly relevant to clinical mood
      disorders and they are well-recognised in the aetiology and maintenance of depression, such
      that depressed individuals are more likely to interpret, focus on and remember negative
      compared to positive emotional cues in self-relevant neuropsychological tasks. Antidepressant
      treatments have been shown to cause early, subconscious positive changes in emotional
      processing biases, which are evident in computerised tasks after one single dose of
      antidepressant. Recent theory suggests that over time this positive change in emotional bias
      contributes to improved mood.

      Since elevated inflammatory markers appear to negatively affect mood and neuropsychological
      function, the investigators believe there is a need to expand our understanding of the
      psychological effects of reducing inflammatory markers. To do so, subjects will be
      administered either a single dose of 200 mg minocycline or placebo, after which they will
      complete a well-validated computerized battery of psychological tasks, which includes
      paradigms such as facial expression recognition, emotional categorization and emotional
      memory tasks that have previously been shown to be sensitive to conventional antidepressant
      treatments in healthy volunteers.

      The results of this study will be compared to effects of common antidepressant treatments
      found using this same model within the investigators' lab and others. If effects are found to
      be comparable, this could not only provide further support for the emotional processing
      theory of antidepressant action, but it could also help to identify novel therapeutic targets
      for new treatments that could benefit depressed patients who do not respond successfully to
      current antidepressants.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Facial Expression Recognition Task
time frame: 2 hours
measure: Emotional Categorization Task
time frame: 2 hours
measure: Emotional Recall Task
time frame: 2 hours
measure: Emotional Recognition Memory Task
time frame: 2 hours
measure: Attentional Dot-Probe
time frame: 2 hours
measure: N-back Task
time frame: 2 hours
measure: Contextual Cueing Task
time frame: 2 hours
measure: Priming Task
time frame: 2 hours
measure: Concentration of the inflammatory marker TNF-alpha in serum Serum inflammatory cytokines and metabolites
time frame: 0 and 4 hours
measure: Concentration of the inflammatory marker IL-6 in serum
time frame: 0 and 4 hours
measure: Concentration of the inflammatory marker C-reactive protein in serum
time frame: 0 and 4 hours
measure: Concentration of the stress hormone cortisol in serum
time frame: 0 and 4hours
measure: Concentration of metabolites (amino acids and lipids) in serum
time frame: 0 and 4 hours
arm group label: Minocycline
arm group type: Experimental
description: single dose of minocycline (200mg)
arm group label: Placebo
arm group type: Placebo Comparator
description: lactose pills (400mg)
intervention type: Drug
intervention name: Minocycline
description: Minocycline (200mg)
arm group label: Minocycline
intervention type: Other
intervention name: placebo
description: Lactose (400mg)
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Minocycline
sharing ipd: No