<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/NCT02196090</url>
  </required_header>
  <id_info>
    <org_study_id>SLAM-RD-001</org_study_id>
    <nct_id>NCT02196090</nct_id>
  </id_info>
  <brief_title>Application of Vagal Stimulation in Exposure and Response Prevention for Obsessive Compulsive Disorder</brief_title>
  <official_title>Application of Vagal Stimulation by Cold Face Mask in Exposure and Response Prevention for Obsessive Compulsive Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>King's College London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>King's College London</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Obsessive Compulsive Disorder (OCD) is a condition associated with recurrent intrusive&#xD;
      distressing thoughts, images and urges compelling the person to perform neutralizing acts or&#xD;
      thoughts to the extent of significantly interfering with their daily activities. The symptoms&#xD;
      of OCD are associated with both subjective and objective signs of distress. Treatment for&#xD;
      Obsessive Compulsive Disorder is often associated with significant subjective distress with&#xD;
      high dropout rates and often only limited improvement. Attempts to reduce distress in anxiety&#xD;
      often focus on re-establishing the sympathovagal balance by enhancing the vagal or&#xD;
      parasympathetic tone and it has been suggested that this can reduce the mobilization&#xD;
      behaviours of fight or flight response and improve emotion regulation. This study will&#xD;
      investigate the effect of a procedure potentially reducing distress and improving outcome of&#xD;
      treatment in inpatients admitted for treatment for OCD to the Anxiety Disorders Residential&#xD;
      Unit. The procedure will be based on increasing vagal tone by application of cold face mask&#xD;
      on 3 consecutive days in addition to the standard Exposure and Response Prevention therapy&#xD;
      (ERP).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. Background&#xD;
&#xD;
           Obsessive Compulsive Disorder (OCD) is a condition associated with recurrent intrusive&#xD;
           distressing thoughts, images and urges compelling the person to perform neutralizing&#xD;
           acts or thoughts to the extent of significantly interfering with their daily activities.&#xD;
           The symptoms of OCD are associated with both subjective and objective signs of distress.&#xD;
           Psychophysiological studies of OCD and other anxiety disorders often report abnormal&#xD;
           sympathovagal balance with decreased parasympathetic or vagal tone and increased&#xD;
           sympathetic tone (Hoehn-Saric et al 1995, Broderick et al 2013, Kawano et al 2012,&#xD;
           Pittig et al 2013, Buhlmann et al 2007, Blechert et al 2007, Friedman and Thayer 1998).&#xD;
&#xD;
           The first line treatment of OCD is Cognitive Behaviour Therapy (CBT) which includes&#xD;
           Exposure and Response Prevention (ERP) when the patient tests out their fears without&#xD;
           responding by compulsive act (NICE Clinical Guideline 31). ERP treatment itself is often&#xD;
           associated with significant subjective distress (Kellner et al 2012) with dropout rates&#xD;
           up to 20% and only minimal improvement in another 20% of patients (Foa 2010). Various&#xD;
           modalities of treatment reducing the subjective and physiological distress have been&#xD;
           used in treatment of anxiety disorders and symptoms (Streeter et al 2012, Miu et al&#xD;
           2009, Gorman et al 2000) and similar approach could increase the rates of improvement&#xD;
           and adherence to ERP treatment in OCD. Most of the attempts to reduce distress in&#xD;
           anxiety focus on re-establishing the sympathovagal balance by enhancing the vagal or&#xD;
           parasympathetic tone and it has been suggested that this can reduce the mobilization&#xD;
           behaviours of fight or flight response and improve emotion regulation (Austin et al&#xD;
           2007). Disgust is an emotion implicated to have significant role on anxiety disorders&#xD;
           such as OCD with contamination fears (Moretz and McKay 2008). It has been shown to have&#xD;
           only limited response to exposure therapy (Olatunji et al 2009) and can be associated&#xD;
           with increased avoidance and reduced compliance with exposures (Olatunji et al 2007)&#xD;
           possibly contributing to poorer treatment outcome. Disgust can be associated with&#xD;
           changes in sympathovagal balance (Ottaviani et al 2013) but the effect of manoeuvres&#xD;
           affecting this balance has not been tested.&#xD;
&#xD;
           Vagal tonus can be increased with specific procedures called vagal manoeuvres. These&#xD;
           include the diving reflex, Valsalva manoeuvre, pressure on the eyeball and carotid sinus&#xD;
           massage, with the diving reflex being one of the most effective (Arnold 1999). The&#xD;
           diving reflex is a phylogenetically ancient physiological phenomenon believed to&#xD;
           facilitate survival after immersion in cold water through bradycardia and peripheral&#xD;
           vasoconstriction redistributing blood flow to vital organs (Gooden 1994). The combined&#xD;
           bradycardia and vasoconstriction effect indicates on complex sympathovagal activation&#xD;
           and the bradycardia itself is believed to be due to central vagal activation (Stemper et&#xD;
           al 2002). The natural trigger for diving reflex includes change in body position, apnoea&#xD;
           and sensation of cold and wet surface on the face and a cold sensation on the face is&#xD;
           sufficient to induce the vagal response. This is believed to be transmitted by the&#xD;
           ophthalmic branch of the trigeminal nerve and can be achieved by using cold compressions&#xD;
           or cold face gel masks (Khurana et al. 1980).&#xD;
&#xD;
           The physiological response during diving reflex can be measured by recording standard&#xD;
           physiological measures such as heart rate, blood pressure or skin conductance. Heart&#xD;
           rate and its interpretation in terms of heart rate variability is becoming more&#xD;
           frequently utilized to evaluate the balance between sympathetic and parasympathetic&#xD;
           nervous system. Most frequently used is the frequency domain approach which allows&#xD;
           differentiating specific frequency bands. The low frequency (LF) band groups the&#xD;
           variability between 0.05-0.15Hz and is believed to represent the sympathetic cardiac&#xD;
           control with slower unmyelinated nerve fibres while the high frequency (HF) band&#xD;
           including frequencies between 0.15-0.4Hz reflects the parasympathetic or vagal control&#xD;
           with faster myelinated nerve fibres (Berntson et al 1997).&#xD;
&#xD;
        2. Aims of the study&#xD;
&#xD;
      The aim of the study is to evaluate the effect of a simple vagal manoeuvre, that is a cold&#xD;
      face gel mask application, on subjective measures of Anxiety, Disgust, Strength of belief in&#xD;
      obsession, Strength of urge to carry out the compulsion, Strength of belief in Theory A/B and&#xD;
      an increase in Feeling of being supported, Readiness to face the fear during the ERP&#xD;
      treatment of OCD by using a single-case series experimental design and to explore the&#xD;
      relationship between subjective measures and sympathovagal balance measured by heart rate&#xD;
      variability. Our hypothesis is that:&#xD;
&#xD;
        1. ERP with application of cold gel face mask (Condition B) will be associated with faster&#xD;
           reduction of visual analogue scales of Anxiety, Disgust, Strength of belief in&#xD;
           obsession, Strength of urge to carry out the compulsion, Strength of belief in Theory&#xD;
           A/B and an increase in Feeling of being supported, Readiness to face the fear compared&#xD;
           to ERP as usual with simply resisting the compulsive behaviour (Condition C).&#xD;
&#xD;
        2. Increase in vagal tonus as documented by heart rate variability measures will correlate&#xD;
           with the effect on visual analogue scales of Anxiety, Disgust, Strength of belief in&#xD;
           obsession, Strength of urge to carry out the compulsion, Strength of belief in Theory&#xD;
           A/B, Feeling of being supported and Readiness to face the fear.&#xD;
&#xD;
      3. Methods&#xD;
&#xD;
      i. Participants: Participants will be recruited from the Anxiety Disorders Residential Unit&#xD;
      (ADRU), Bethlem Royal Hospital. All patients admitted to ADRU have the opportunity to consent&#xD;
      to be contacted about participating in research studies. Only patients admitted to ADRU for&#xD;
      treatment of OCD who provided such initial consent will be approached by Dr Roman Duncko&#xD;
      regarding the written informed consent to participate in the present study.&#xD;
&#xD;
      ii. Procedure and Design: On each day of the study, therapy will begin with the Baseline&#xD;
      phase (Condition A) and record the psychological (visual analogue scales of Anxiety, Disgust,&#xD;
      Belief in obsession, Strength of urge for compulsion, Strength of belief in Theory A/B,&#xD;
      Feeling of being supported, Readiness to face the fear) and physiological measures (HR&#xD;
      recording) on 3-5 consecutive 5min intervals or until stable baseline measures are achieved.&#xD;
      After that, the participant will proceed with the Intervention phase by applying ERP with the&#xD;
      use of triggers as identified on their individual hierarchy. Each ERP session will follow the&#xD;
      same structure by first obtaining the session baseline at 3 time points, then exposure to&#xD;
      trigger and continue with preventing the response while applying the cold face mask for 5&#xD;
      minutes (Condition B) or without using the face mask (Condition C). Psychological and&#xD;
      physiological measures will be obtained in 5 minute intervals until return to session&#xD;
      baseline. ERP sessions will follow in alternating order for 4 sessions per day (Day 1: ABCBC,&#xD;
      Day 2: ACBCB, Day 3: ABCBC). All baseline and exposure measures will be recorded by the&#xD;
      investigator who will by accompanying the participant during the procedure. Cold face gel&#xD;
      masks will be stored in refrigerator at the ADRU and will be available to the participant as&#xD;
      required.&#xD;
&#xD;
      iii. Psychological measures: Visual analogue scales for measurement of severity of Anxiety,&#xD;
      Disgust, Strength of belief in obsession, Strength of urge to carry out the compulsion,&#xD;
      Strength of belief in theory A/B, Strength of belief in Theory A/B, Feeling of being&#xD;
      supported, Readiness to face the fear will be used by the participant at time points as&#xD;
      specified above. In addition to this the participant will be assessed for their clinical&#xD;
      symptoms (YBOCS, OCI) on weekly basis as part of their standard treatment plan.&#xD;
&#xD;
      On the last day of the study, participants will be asked to complete the Client Satisfaction&#xD;
      Questionnaire based on (Larsen et al 1979) to explore the feasibility and acceptability of&#xD;
      the cold face gel mask application during ERP.&#xD;
&#xD;
      iv. Physiological measures: Heart rate variability analysis will be performed on data&#xD;
      recorded with a Polar RS800CX heart rate monitor using a H2 chest sensor. Polar monitors have&#xD;
      been tested against standard clinical ECG equipment and found to be suitable for heart rate&#xD;
      variability analysis (Vanderlei et al 2008). In the morning of the study day, the&#xD;
      participants will place the Polar heart rate sensor on their chest using the elastic strap.&#xD;
      They will be instructed how to use the heart rate monitor watch Polar RS800CX to record the&#xD;
      heart rate and press the mark recording button at specific times during each procedure. At&#xD;
      the end of each study day, the data will be downloaded from the heart rate monitor watch and&#xD;
      3 time intervals of 2 minutes will be identified: at the beginning of the condition - time 0,&#xD;
      at the beginning of the procedure - time 15, at the end of the condition - time 45. Time&#xD;
      intervals will be screened for artefacts and used for heart rate variability analysis using&#xD;
      standalone analysis software (Niskanen et al 2004). Variables selected for analysis will&#xD;
      include heart rate per minute, time domain measures (RMSSD, NN50) and frequency domain&#xD;
      measures (nLF at 0.05-0.15Hz, nHF at 0.15-0.04Hz, LF/HF).&#xD;
&#xD;
      v. Data analysis: Data will be initially evaluated by visual inspection for each participant&#xD;
      individually. After that, values obtained for a specific time interval and phase will be&#xD;
      averaged among all participants and again evaluated by visual inspection. Percentage of&#xD;
      non-overlapping data analysis will be performed to detect statistically significant change&#xD;
      between the baseline and intervention phase. Pearson's correlation will be used for&#xD;
      correlation analyses.&#xD;
&#xD;
      4. Project timetable&#xD;
&#xD;
      The project is planned to run for 6-12 months depending on the rate of recruitment of&#xD;
      participants.&#xD;
&#xD;
      5. Expertise in team&#xD;
&#xD;
      Dr David Veale is a consultant psychiatrist in Cognitive Behaviour Therapy at the South&#xD;
      London and Maudsley Trust and a Honorary Senior Lecturer at the Institute of Psychiatry,&#xD;
      Kings College London. Specialisms include obsessive compulsive disorder.&#xD;
&#xD;
      Dr Roman Duncko, PhD is a ST5 trainee in General Adult Psychiatry at the South London and&#xD;
      Maudsley Trust with long-term research interest in anxiety disorders and autonomic nervous&#xD;
      system function.&#xD;
&#xD;
      6. Ethical considerations&#xD;
&#xD;
      All ethical considerations are outlined in the Participant Information and Consent Form that&#xD;
      will be distributed to participants. All patients admitted to ARDU who fulfil the inclusion&#xD;
      criteria will be approached about participating in the study. All participants will require&#xD;
      signing an informed consent to participate. All information and data obtained during the&#xD;
      study will be kept in strict confidence. Upon recruitment, every participant will be assigned&#xD;
      an anonymous code and the lists linking the code with personal identifying information will&#xD;
      be kept secure and separate from the data. Only the Principal Investigator and researchers&#xD;
      authorized by the PI will have access to the identifying lists. Every participant will&#xD;
      undergo the same procedures with slightly variable order. No deception will be used and&#xD;
      participants will be informed as to exactly what the study is about. All participants will be&#xD;
      informed at the time of providing consent to participate that they can withdraw from the&#xD;
      study at any time and that this will not affect the care they will receive.&#xD;
&#xD;
      7. Dissemination and implementation&#xD;
&#xD;
      Results of the study will be used for poster and/or oral presentations at suitable&#xD;
      conferences and for preparing a manuscript for submission in a scientific journal. Depending&#xD;
      on the outcome of the study further research will be planned to evaluate the effect of cold&#xD;
      face gel mask in a study with randomized control trial design.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>July 2014</start_date>
  <completion_date type="Anticipated">February 2016</completion_date>
  <primary_completion_date type="Anticipated">February 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Visual analogue scales at baseline</measure>
    <time_frame>This measure will be assessed with every exposure on each day of the study at baseline - 5 minutes prior to exposure.</time_frame>
    <description>Rates of Anxiety, Disgust, Strength of belief in obsession, Strength of urge to carry out the compulsion, Strength of belief in theory A/B, Strength of belief in Theory A/B, Feeling of being supported, Readiness to face the fear obtained from visual analogue scales.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Visual analogue scales at exposure</measure>
    <time_frame>This measure will be assessed with every exposure on each day of the study immediately after finishing the exposure</time_frame>
    <description>Rates of Anxiety, Disgust, Strength of belief in obsession, Strength of urge to carry out the compulsion, Strength of belief in theory A/B, Strength of belief in Theory A/B, Feeling of being supported, Readiness to face the fear obtained from visual analogue scales.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Visual analogue scales 5 minutes post exposure</measure>
    <time_frame>This measure will be assessed with every exposure on each day of the study at 5 minutes after the exposure.</time_frame>
    <description>Rates of Anxiety, Disgust, Strength of belief in obsession, Strength of urge to carry out the compulsion, Strength of belief in theory A/B, Strength of belief in Theory A/B, Feeling of being supported, Readiness to face the fear obtained from visual analogue scales.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Visual analogue scales 10 minutes post exposure</measure>
    <time_frame>This measure will be assessed with every exposure on each day of the study at 10 minutes after the exposure.</time_frame>
    <description>Rates of Anxiety, Disgust, Strength of belief in obsession, Strength of urge to carry out the compulsion, Strength of belief in theory A/B, Strength of belief in Theory A/B, Feeling of being supported, Readiness to face the fear obtained from visual analogue scales.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Visual analogue scales 15 minutes post exposure</measure>
    <time_frame>This measure will be assessed with every exposure on each day of the study at 15 minutes after the exposure.</time_frame>
    <description>Rates of Anxiety, Disgust, Strength of belief in obsession, Strength of urge to carry out the compulsion, Strength of belief in theory A/B, Strength of belief in Theory A/B, Feeling of being supported, Readiness to face the fear obtained from visual analogue scales.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Heart rate variability measures</measure>
    <time_frame>Heart rate variability measures will be analyzed for specific timeintervals at baseline, during exposure and at three time points after the exposure, at 5, 10 and 15 minutes after exposure.</time_frame>
    <description>Heart rate will be recorded during each ERP session. Hear rate and Heart Rate Variability (HRV) measures will be analyzed in 2 minute intervals corresponding with the timepoints of filling in the VAS at baseline, during the exposure and at three time points after the exposure, at 5, 10 and 15 minutes after the exposure. The Heart Rate Variability measures will include heart rate per minute, time domain measures (RMSSD, NN50) and frequency domain measures (nLF at 0.05-0.15Hz, nHF at 0.15-0.04Hz, LF/HF).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Symptom severity measures</measure>
    <time_frame>These measures will be assessed within 1 week prior to the beginning of study and within 1 week after the last ERP session.</time_frame>
    <description>YBOCS and OCI questionnaires</description>
  </other_outcome>
  <other_outcome>
    <measure>Client Satisfaction Questionnaire</measure>
    <time_frame>This measure will be assessed within 1 week of completing the study.</time_frame>
    <description>Client Satisfaction Questionnaire used to explore the feasibility and acceptability of the cold face gel mask application during ERP</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Obsessive Compulsive Disorder</condition>
  <arm_group>
    <arm_group_label>Single arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Study uses the single case series design with only one arm. All participants in the one arm will have procedures with treatment as usual (Exposure and Response Prevention) alternating with procedures including the vagal maneuver (Cold Face Gel Mask).</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Exposure and Response Prevention</intervention_name>
    <description>A procedure where patients with OCD test out their fears without responding by compulsive act.</description>
    <arm_group_label>Single arm</arm_group_label>
    <other_name>ERP</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Cold face gel mask</intervention_name>
    <description>Temporary application of cold eye mask on the face is commonly used for relaxation purpose.</description>
    <arm_group_label>Single arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age over 18 years&#xD;
&#xD;
          -  signed informed consent&#xD;
&#xD;
          -  established diagnosis of OCD&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  patients who do not understand English sufficiently to complete the questionnaires&#xD;
&#xD;
          -  patients who do not have mental capacity to provide informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Roman Duncko, PhD MRCPsych</last_name>
    <role>Principal Investigator</role>
    <affiliation>South London and Mausdley NHS Trust</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Roman Duncko, PhD MRCPsych</last_name>
    <phone>+44(0)2032284545</phone>
    <email>roman.duncko@slam.nhs.uk</email>
  </overall_contact>
  <location>
    <facility>
      <name>Anxiety Disorders Residential Unit, Bethlem Royal Hospital</name>
      <address>
        <city>Beckenham</city>
        <state>Kent</state>
        <zip>BR3 3BX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Roman Duncko, PhD MRCPsych</last_name>
      <phone>+44(0)2032284545</phone>
      <email>roman.duncko@slam.nhs.uk</email>
    </contact>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
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  </reference>
  <reference>
    <citation>NICE Clinical Guideline 31: Obsessive-compulsive disorder. Core interventions in the treatment of obsessive compulsive disorder and body dysmorphic disorder. www.nice.org.uk/cg31</citation>
  </reference>
  <reference>
    <citation>Niskanen JP, Tarvainen MP, Ranta-Aho PO, Karjalainen PA. Software for advanced HRV analysis. Comput Methods Programs Biomed. 2004 Oct;76(1):73-81. doi: 10.1016/j.cmpb.2004.03.004.</citation>
    <PMID>15313543</PMID>
  </reference>
  <reference>
    <citation>Olatunji BO, Lohr JM, Sawchuk CN, Tolin DF. Multimodal assessment of disgust in contamination-related obsessive-compulsive disorder. Behav Res Ther. 2007 Feb;45(2):263-76. doi: 10.1016/j.brat.2006.03.004. Epub 2006 May 12.</citation>
    <PMID>16697976</PMID>
  </reference>
  <reference>
    <citation>Olatunji BO, Wolitzky-Taylor KB, Willems J, Lohr JM, Armstrong T. Differential habituation of fear and disgust during repeated exposure to threat-relevant stimuli in contamination-based OCD: an analogue study. J Anxiety Disord. 2009 Jan;23(1):118-23. doi: 10.1016/j.janxdis.2008.04.006. Epub 2008 May 3.</citation>
    <PMID>18541403</PMID>
  </reference>
  <reference>
    <citation>Ottaviani C, Mancini F, Petrocchi N, Medea B, Couyoumdjian A. Autonomic correlates of physical and moral disgust. Int J Psychophysiol. 2013 Jul;89(1):57-62. doi: 10.1016/j.ijpsycho.2013.05.003. Epub 2013 May 15.</citation>
    <PMID>23684734</PMID>
  </reference>
  <reference>
    <citation>Pittig A, Arch JJ, Lam CW, Craske MG. Heart rate and heart rate variability in panic, social anxiety, obsessive-compulsive, and generalized anxiety disorders at baseline and in response to relaxation and hyperventilation. Int J Psychophysiol. 2013 Jan;87(1):19-27. doi: 10.1016/j.ijpsycho.2012.10.012. Epub 2012 Oct 27.</citation>
    <PMID>23107994</PMID>
  </reference>
  <reference>
    <citation>Stemper B, Hilz MJ, Rauhut U, Neundorfer B. Evaluation of cold face test bradycardia by means of spectral analysis. Clin Auton Res. 2002 Apr;12(2):78-83. doi: 10.1007/s102860200024.</citation>
    <PMID>12102454</PMID>
  </reference>
  <reference>
    <citation>Streeter CC, Gerbarg PL, Saper RB, Ciraulo DA, Brown RP. Effects of yoga on the autonomic nervous system, gamma-aminobutyric-acid, and allostasis in epilepsy, depression, and post-traumatic stress disorder. Med Hypotheses. 2012 May;78(5):571-9. doi: 10.1016/j.mehy.2012.01.021. Epub 2012 Feb 24.</citation>
    <PMID>22365651</PMID>
  </reference>
  <reference>
    <citation>Vanderlei LC, Silva RA, Pastre CM, Azevedo FM, Godoy MF. Comparison of the Polar S810i monitor and the ECG for the analysis of heart rate variability in the time and frequency domains. Braz J Med Biol Res. 2008 Oct;41(10):854-9. doi: 10.1590/s0100-879x2008005000039. Epub 2008 Sep 30.</citation>
    <PMID>18853042</PMID>
  </reference>
  <verification_date>February 2016</verification_date>
  <study_first_submitted>June 24, 2014</study_first_submitted>
  <study_first_submitted_qc>July 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 21, 2014</study_first_posted>
  <last_update_submitted>February 26, 2016</last_update_submitted>
  <last_update_submitted_qc>February 26, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 29, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>OCD, Exposure and Response Prevention, Vagal Stimulation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Compulsive Personality Disorder</mesh_term>
    <mesh_term>Obsessive-Compulsive Disorder</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>September 20, 2021</submitted>
    <returned>October 15, 2021</returned>
    <submitted>October 21, 2021</submitted>
    <submission_canceled>October 21, 2021</submission_canceled>
    <submitted>October 25, 2021</submitted>
    <returned>December 2, 2021</returned>
    <submitted>January 10, 2022</submitted>
    <returned>March 8, 2022</returned>
  </pending_results>
  <!-- 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/NCT02196090
org study id: SLAM-RD-001
nct id: NCT02196090
lead sponsor: 
has dmc: No
Obsessive Compulsive Disorder (OCD) is a condition associated with recurrent intrusive
      distressing thoughts, images and urges compelling the person to perform neutralizing acts or
      thoughts to the extent of significantly interfering with their daily activities. The symptoms
      of OCD are associated with both subjective and objective signs of distress. Treatment for
      Obsessive Compulsive Disorder is often associated with significant subjective distress with
      high dropout rates and often only limited improvement. Attempts to reduce distress in anxiety
      often focus on re-establishing the sympathovagal balance by enhancing the vagal or
      parasympathetic tone and it has been suggested that this can reduce the mobilization
      behaviours of fight or flight response and improve emotion regulation. This study will
      investigate the effect of a procedure potentially reducing distress and improving outcome of
      treatment in inpatients admitted for treatment for OCD to the Anxiety Disorders Residential
      Unit. The procedure will be based on increasing vagal tone by application of cold face mask
      on 3 consecutive days in addition to the standard Exposure and Response Prevention therapy
      (ERP).
1. Background

           Obsessive Compulsive Disorder (OCD) is a condition associated with recurrent intrusive
           distressing thoughts, images and urges compelling the person to perform neutralizing
           acts or thoughts to the extent of significantly interfering with their daily activities.
           The symptoms of OCD are associated with both subjective and objective signs of distress.
           Psychophysiological studies of OCD and other anxiety disorders often report abnormal
           sympathovagal balance with decreased parasympathetic or vagal tone and increased
           sympathetic tone (Hoehn-Saric et al 1995, Broderick et al 2013, Kawano et al 2012,
           Pittig et al 2013, Buhlmann et al 2007, Blechert et al 2007, Friedman and Thayer 1998).

           The first line treatment of OCD is Cognitive Behaviour Therapy (CBT) which includes
           Exposure and Response Prevention (ERP) when the patient tests out their fears without
           responding by compulsive act (NICE Clinical Guideline 31). ERP treatment itself is often
           associated with significant subjective distress (Kellner et al 2012) with dropout rates
           up to 20% and only minimal improvement in another 20% of patients (Foa 2010). Various
           modalities of treatment reducing the subjective and physiological distress have been
           used in treatment of anxiety disorders and symptoms (Streeter et al 2012, Miu et al
           2009, Gorman et al 2000) and similar approach could increase the rates of improvement
           and adherence to ERP treatment in OCD. Most of the attempts to reduce distress in
           anxiety focus on re-establishing the sympathovagal balance by enhancing the vagal or
           parasympathetic tone and it has been suggested that this can reduce the mobilization
           behaviours of fight or flight response and improve emotion regulation (Austin et al
           2007). Disgust is an emotion implicated to have significant role on anxiety disorders
           such as OCD with contamination fears (Moretz and McKay 2008). It has been shown to have
           only limited response to exposure therapy (Olatunji et al 2009) and can be associated
           with increased avoidance and reduced compliance with exposures (Olatunji et al 2007)
           possibly contributing to poorer treatment outcome. Disgust can be associated with
           changes in sympathovagal balance (Ottaviani et al 2013) but the effect of manoeuvres
           affecting this balance has not been tested.

           Vagal tonus can be increased with specific procedures called vagal manoeuvres. These
           include the diving reflex, Valsalva manoeuvre, pressure on the eyeball and carotid sinus
           massage, with the diving reflex being one of the most effective (Arnold 1999). The
           diving reflex is a phylogenetically ancient physiological phenomenon believed to
           facilitate survival after immersion in cold water through bradycardia and peripheral
           vasoconstriction redistributing blood flow to vital organs (Gooden 1994). The combined
           bradycardia and vasoconstriction effect indicates on complex sympathovagal activation
           and the bradycardia itself is believed to be due to central vagal activation (Stemper et
           al 2002). The natural trigger for diving reflex includes change in body position, apnoea
           and sensation of cold and wet surface on the face and a cold sensation on the face is
           sufficient to induce the vagal response. This is believed to be transmitted by the
           ophthalmic branch of the trigeminal nerve and can be achieved by using cold compressions
           or cold face gel masks (Khurana et al. 1980).

           The physiological response during diving reflex can be measured by recording standard
           physiological measures such as heart rate, blood pressure or skin conductance. Heart
           rate and its interpretation in terms of heart rate variability is becoming more
           frequently utilized to evaluate the balance between sympathetic and parasympathetic
           nervous system. Most frequently used is the frequency domain approach which allows
           differentiating specific frequency bands. The low frequency (LF) band groups the
           variability between 0.05-0.15Hz and is believed to represent the sympathetic cardiac
           control with slower unmyelinated nerve fibres while the high frequency (HF) band
           including frequencies between 0.15-0.4Hz reflects the parasympathetic or vagal control
           with faster myelinated nerve fibres (Berntson et al 1997).

        2. Aims of the study

      The aim of the study is to evaluate the effect of a simple vagal manoeuvre, that is a cold
      face gel mask application, on subjective measures of Anxiety, Disgust, Strength of belief in
      obsession, Strength of urge to carry out the compulsion, Strength of belief in Theory A/B and
      an increase in Feeling of being supported, Readiness to face the fear during the ERP
      treatment of OCD by using a single-case series experimental design and to explore the
      relationship between subjective measures and sympathovagal balance measured by heart rate
      variability. Our hypothesis is that:

        1. ERP with application of cold gel face mask (Condition B) will be associated with faster
           reduction of visual analogue scales of Anxiety, Disgust, Strength of belief in
           obsession, Strength of urge to carry out the compulsion, Strength of belief in Theory
           A/B and an increase in Feeling of being supported, Readiness to face the fear compared
           to ERP as usual with simply resisting the compulsive behaviour (Condition C).

        2. Increase in vagal tonus as documented by heart rate variability measures will correlate
           with the effect on visual analogue scales of Anxiety, Disgust, Strength of belief in
           obsession, Strength of urge to carry out the compulsion, Strength of belief in Theory
           A/B, Feeling of being supported and Readiness to face the fear.

      3. Methods

      i. Participants: Participants will be recruited from the Anxiety Disorders Residential Unit
      (ADRU), Bethlem Royal Hospital. All patients admitted to ADRU have the opportunity to consent
      to be contacted about participating in research studies. Only patients admitted to ADRU for
      treatment of OCD who provided such initial consent will be approached by Dr Roman Duncko
      regarding the written informed consent to participate in the present study.

      ii. Procedure and Design: On each day of the study, therapy will begin with the Baseline
      phase (Condition A) and record the psychological (visual analogue scales of Anxiety, Disgust,
      Belief in obsession, Strength of urge for compulsion, Strength of belief in Theory A/B,
      Feeling of being supported, Readiness to face the fear) and physiological measures (HR
      recording) on 3-5 consecutive 5min intervals or until stable baseline measures are achieved.
      After that, the participant will proceed with the Intervention phase by applying ERP with the
      use of triggers as identified on their individual hierarchy. Each ERP session will follow the
      same structure by first obtaining the session baseline at 3 time points, then exposure to
      trigger and continue with preventing the response while applying the cold face mask for 5
      minutes (Condition B) or without using the face mask (Condition C). Psychological and
      physiological measures will be obtained in 5 minute intervals until return to session
      baseline. ERP sessions will follow in alternating order for 4 sessions per day (Day 1: ABCBC,
      Day 2: ACBCB, Day 3: ABCBC). All baseline and exposure measures will be recorded by the
      investigator who will by accompanying the participant during the procedure. Cold face gel
      masks will be stored in refrigerator at the ADRU and will be available to the participant as
      required.

      iii. Psychological measures: Visual analogue scales for measurement of severity of Anxiety,
      Disgust, Strength of belief in obsession, Strength of urge to carry out the compulsion,
      Strength of belief in theory A/B, Strength of belief in Theory A/B, Feeling of being
      supported, Readiness to face the fear will be used by the participant at time points as
      specified above. In addition to this the participant will be assessed for their clinical
      symptoms (YBOCS, OCI) on weekly basis as part of their standard treatment plan.

      On the last day of the study, participants will be asked to complete the Client Satisfaction
      Questionnaire based on (Larsen et al 1979) to explore the feasibility and acceptability of
      the cold face gel mask application during ERP.

      iv. Physiological measures: Heart rate variability analysis will be performed on data
      recorded with a Polar RS800CX heart rate monitor using a H2 chest sensor. Polar monitors have
      been tested against standard clinical ECG equipment and found to be suitable for heart rate
      variability analysis (Vanderlei et al 2008). In the morning of the study day, the
      participants will place the Polar heart rate sensor on their chest using the elastic strap.
      They will be instructed how to use the heart rate monitor watch Polar RS800CX to record the
      heart rate and press the mark recording button at specific times during each procedure. At
      the end of each study day, the data will be downloaded from the heart rate monitor watch and
      3 time intervals of 2 minutes will be identified: at the beginning of the condition - time 0,
      at the beginning of the procedure - time 15, at the end of the condition - time 45. Time
      intervals will be screened for artefacts and used for heart rate variability analysis using
      standalone analysis software (Niskanen et al 2004). Variables selected for analysis will
      include heart rate per minute, time domain measures (RMSSD, NN50) and frequency domain
      measures (nLF at 0.05-0.15Hz, nHF at 0.15-0.04Hz, LF/HF).

      v. Data analysis: Data will be initially evaluated by visual inspection for each participant
      individually. After that, values obtained for a specific time interval and phase will be
      averaged among all participants and again evaluated by visual inspection. Percentage of
      non-overlapping data analysis will be performed to detect statistically significant change
      between the baseline and intervention phase. Pearson's correlation will be used for
      correlation analyses.

      4. Project timetable

      The project is planned to run for 6-12 months depending on the rate of recruitment of
      participants.

      5. Expertise in team

      Dr David Veale is a consultant psychiatrist in Cognitive Behaviour Therapy at the South
      London and Maudsley Trust and a Honorary Senior Lecturer at the Institute of Psychiatry,
      Kings College London. Specialisms include obsessive compulsive disorder.

      Dr Roman Duncko, PhD is a ST5 trainee in General Adult Psychiatry at the South London and
      Maudsley Trust with long-term research interest in anxiety disorders and autonomic nervous
      system function.

      6. Ethical considerations

      All ethical considerations are outlined in the Participant Information and Consent Form that
      will be distributed to participants. All patients admitted to ARDU who fulfil the inclusion
      criteria will be approached about participating in the study. All participants will require
      signing an informed consent to participate. All information and data obtained during the
      study will be kept in strict confidence. Upon recruitment, every participant will be assigned
      an anonymous code and the lists linking the code with personal identifying information will
      be kept secure and separate from the data. Only the Principal Investigator and researchers
      authorized by the PI will have access to the identifying lists. Every participant will
      undergo the same procedures with slightly variable order. No deception will be used and
      participants will be informed as to exactly what the study is about. All participants will be
      informed at the time of providing consent to participate that they can withdraw from the
      study at any time and that this will not affect the care they will receive.

      7. Dissemination and implementation

      Results of the study will be used for poster and/or oral presentations at suitable
      conferences and for preparing a manuscript for submission in a scientific journal. Depending
      on the outcome of the study further research will be planned to evaluate the effect of cold
      face gel mask in a study with randomized control trial design.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Visual analogue scales at baseline
time frame: This measure will be assessed with every exposure on each day of the study at baseline - 5 minutes prior to exposure.
description: Rates of Anxiety, Disgust, Strength of belief in obsession, Strength of urge to carry out the compulsion, Strength of belief in theory A/B, Strength of belief in Theory A/B, Feeling of being supported, Readiness to face the fear obtained from visual analogue scales.
measure: Visual analogue scales at exposure
time frame: This measure will be assessed with every exposure on each day of the study immediately after finishing the exposure
description: Rates of Anxiety, Disgust, Strength of belief in obsession, Strength of urge to carry out the compulsion, Strength of belief in theory A/B, Strength of belief in Theory A/B, Feeling of being supported, Readiness to face the fear obtained from visual analogue scales.
measure: Visual analogue scales 5 minutes post exposure
time frame: This measure will be assessed with every exposure on each day of the study at 5 minutes after the exposure.
description: Rates of Anxiety, Disgust, Strength of belief in obsession, Strength of urge to carry out the compulsion, Strength of belief in theory A/B, Strength of belief in Theory A/B, Feeling of being supported, Readiness to face the fear obtained from visual analogue scales.
measure: Visual analogue scales 10 minutes post exposure
time frame: This measure will be assessed with every exposure on each day of the study at 10 minutes after the exposure.
description: Rates of Anxiety, Disgust, Strength of belief in obsession, Strength of urge to carry out the compulsion, Strength of belief in theory A/B, Strength of belief in Theory A/B, Feeling of being supported, Readiness to face the fear obtained from visual analogue scales.
measure: Visual analogue scales 15 minutes post exposure
time frame: This measure will be assessed with every exposure on each day of the study at 15 minutes after the exposure.
description: Rates of Anxiety, Disgust, Strength of belief in obsession, Strength of urge to carry out the compulsion, Strength of belief in theory A/B, Strength of belief in Theory A/B, Feeling of being supported, Readiness to face the fear obtained from visual analogue scales.
measure: Heart rate variability measures
time frame: Heart rate variability measures will be analyzed for specific timeintervals at baseline, during exposure and at three time points after the exposure, at 5, 10 and 15 minutes after exposure.
description: Heart rate will be recorded during each ERP session. Hear rate and Heart Rate Variability (HRV) measures will be analyzed in 2 minute intervals corresponding with the timepoints of filling in the VAS at baseline, during the exposure and at three time points after the exposure, at 5, 10 and 15 minutes after the exposure. The Heart Rate Variability measures will include heart rate per minute, time domain measures (RMSSD, NN50) and frequency domain measures (nLF at 0.05-0.15Hz, nHF at 0.15-0.04Hz, LF/HF).
measure: Symptom severity measures
time frame: These measures will be assessed within 1 week prior to the beginning of study and within 1 week after the last ERP session.
description: YBOCS and OCI questionnaires
measure: Client Satisfaction Questionnaire
time frame: This measure will be assessed within 1 week of completing the study.
description: Client Satisfaction Questionnaire used to explore the feasibility and acceptability of the cold face gel mask application during ERP
arm group label: Single arm
arm group type: Experimental
description: Study uses the single case series design with only one arm. All participants in the one arm will have procedures with treatment as usual (Exposure and Response Prevention) alternating with procedures including the vagal maneuver (Cold Face Gel Mask).
intervention type: Behavioral
intervention name: Exposure and Response Prevention
description: A procedure where patients with OCD test out their fears without responding by compulsive act.
arm group label: Single arm
other name: ERP
intervention type: Device
intervention name: Cold face gel mask
description: Temporary application of cold eye mask on the face is commonly used for relaxation purpose.
arm group label: Single arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Roman Duncko, PhD MRCPsych
role: Principal Investigator
affiliation: South London and Mausdley NHS Trust
last name: Roman Duncko, PhD MRCPsych
phone: +44(0)2032284545
email: roman.duncko@slam.nhs.uk
facility: 
status: Recruiting
contact: 
country: United Kingdom
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citation: Niskanen JP, Tarvainen MP, Ranta-Aho PO, Karjalainen PA. Software for advanced HRV analysis. Comput Methods Programs Biomed. 2004 Oct;76(1):73-81. doi: 10.1016/j.cmpb.2004.03.004.
PMID: 15313543
citation: Olatunji BO, Lohr JM, Sawchuk CN, Tolin DF. Multimodal assessment of disgust in contamination-related obsessive-compulsive disorder. Behav Res Ther. 2007 Feb;45(2):263-76. doi: 10.1016/j.brat.2006.03.004. Epub 2006 May 12.
PMID: 16697976
citation: Olatunji BO, Wolitzky-Taylor KB, Willems J, Lohr JM, Armstrong T. Differential habituation of fear and disgust during repeated exposure to threat-relevant stimuli in contamination-based OCD: an analogue study. J Anxiety Disord. 2009 Jan;23(1):118-23. doi: 10.1016/j.janxdis.2008.04.006. Epub 2008 May 3.
PMID: 18541403
citation: Ottaviani C, Mancini F, Petrocchi N, Medea B, Couyoumdjian A. Autonomic correlates of physical and moral disgust. Int J Psychophysiol. 2013 Jul;89(1):57-62. doi: 10.1016/j.ijpsycho.2013.05.003. Epub 2013 May 15.
PMID: 23684734
citation: Pittig A, Arch JJ, Lam CW, Craske MG. Heart rate and heart rate variability in panic, social anxiety, obsessive-compulsive, and generalized anxiety disorders at baseline and in response to relaxation and hyperventilation. Int J Psychophysiol. 2013 Jan;87(1):19-27. doi: 10.1016/j.ijpsycho.2012.10.012. Epub 2012 Oct 27.
PMID: 23107994
citation: Stemper B, Hilz MJ, Rauhut U, Neundorfer B. Evaluation of cold face test bradycardia by means of spectral analysis. Clin Auton Res. 2002 Apr;12(2):78-83. doi: 10.1007/s102860200024.
PMID: 12102454
citation: Streeter CC, Gerbarg PL, Saper RB, Ciraulo DA, Brown RP. Effects of yoga on the autonomic nervous system, gamma-aminobutyric-acid, and allostasis in epilepsy, depression, and post-traumatic stress disorder. Med Hypotheses. 2012 May;78(5):571-9. doi: 10.1016/j.mehy.2012.01.021. Epub 2012 Feb 24.
PMID: 22365651
citation: Vanderlei LC, Silva RA, Pastre CM, Azevedo FM, Godoy MF. Comparison of the Polar S810i monitor and the ECG for the analysis of heart rate variability in the time and frequency domains. Braz J Med Biol Res. 2008 Oct;41(10):854-9. doi: 10.1590/s0100-879x2008005000039. Epub 2008 Sep 30.
PMID: 18853042
responsible party type: Sponsor
mesh term: Compulsive Personality Disorder
mesh term: Obsessive-Compulsive Disorder
submitted: September 20, 2021
returned: October 15, 2021
submitted: October 21, 2021
submission canceled: October 21, 2021
submitted: October 25, 2021
returned: December 2, 2021
submitted: January 10, 2022
returned: March 8, 2022