<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/NCT04414033</url>
  </required_header>
  <id_info>
    <org_study_id>22012020</org_study_id>
    <nct_id>NCT04414033</nct_id>
  </id_info>
  <brief_title>Bubble: A New VR-AI Way of Treatment for Hot Flashes in Women With Breast Cancer</brief_title>
  <official_title>Bubble: A New VR-AI Way of Treatment for Hot Flashes in Women With Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bar-Ilan University, Israel</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hematology and Oncology Specialists</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Bar-Ilan University, Israel</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>
      This study evaluates the potential of a unique artificial intelligence-virtual reality&#xD;
      intervention called Bubble, to reduce the number and intensity of hot flashes and their&#xD;
      accompanying psychological symptoms in women, aged 28-55, with breast cancer. A sample of 37&#xD;
      women with breast cancer were selected to the study. Participants were asked to answer a&#xD;
      survey before and after using Bubble. The treatment period was 24 days. The findings are&#xD;
      positive and show that the use of Bubble help to reduce several psychological symptoms&#xD;
      connected to hot flashes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Breast cancer is the most common cancer in women and the leading cause of death in women aged&#xD;
      &lt; 55 years . Hot flashes are experienced by about 52% of perimenopausal women. After breast&#xD;
      cancer, this may increase to 70%. Hot flash is a subjective sensation of heat that is&#xD;
      associated with objective signs of cutaneous vasodilatation and a subsequent drop in core&#xD;
      temperature. The hot flash may be accompanied by physiological symptoms as sweating,&#xD;
      flashing, palpitations, and night sweat. As well as by psychological symptoms as anxiety,&#xD;
      irritability, and even panic. Hot flashes and night sweats (HF/NS) affect 65-85% of breast&#xD;
      cancer survivors and are associated with sleep problems and reduced quality of life.&#xD;
&#xD;
      It is well known that estrogen largely alleviates vasomotor symptoms, however concerns&#xD;
      regarding its use in women, with or without breast cancer, has led to extensive research&#xD;
      efforts to find well tolerated and efficient nonhormonal interventions. Postmenopausal women&#xD;
      and breast cancer survivors experience psychological, spiritual, sleep, and cognitive&#xD;
      dysfunction beyond what could be attributable to vasomotor symptoms alone. Therefore, an&#xD;
      integrative intervention that can address multiple symptoms is an important patient-centric&#xD;
      strategy.&#xD;
&#xD;
      These days a growing body of research has been dedicated to mind-body interventions. These&#xD;
      interventions include yoga, hypnosis, relaxation-training/paced respiration,&#xD;
      mindfulness-based stress reduction (MBSR), and cognitive behavioral therapy (CBT). In&#xD;
      practice, a previous study demonstrated that distressing or problematic hot flashes were&#xD;
      predicted by depression, anxiety, and low self-image, but not by the frequency of the hot&#xD;
      flashes. Therefore, women with the same amount of hot flashes may have different and diverse&#xD;
      emotional responses to their hot flashes. This psychosocial aspect plays a role in the&#xD;
      distress or can be related to the symptom as well as to the person's will to do something&#xD;
      about his situation. Cognitive behavioral therapy has a long and well documented history of&#xD;
      efficacy related to distress, sleep, and psychological aspects of coping with many of life's&#xD;
      challenges. A study showed that a brief, mindfulness-based intervention demonstrated&#xD;
      preliminary short-term efficacy in reducing stress, behavioral symptoms, and proinflammatory&#xD;
      signaling in younger breast cancer survivors. Also, research indicated that relaxation&#xD;
      training reduced the incidence and severity of hot flashes and the distress caused by the&#xD;
      flashes in women with primary breast cancer compered to control group.&#xD;
&#xD;
      Virtual reality (VR) is a computer technology that uses virtual reality headsets or&#xD;
      multi-projected environments, sometimes in combination with physical environments or props,&#xD;
      to generate realistic images, sounds and other sensations that simulate a user's physical&#xD;
      presence in a virtual or imaginary environment. Today there are two main categories of VR,&#xD;
      immersive and non-immersive. Immersion or presence can be regarded as a variable that can&#xD;
      influence the effects on the attention of users. Full immersion is reached by a head mounted&#xD;
      display, which blocks the users' view of the real world and presents patients with a view of&#xD;
      a computer-generated world instead. This technology may offer subjects a safe environment.&#xD;
&#xD;
      A review of 19 studies reporting the use of VR in therapies related to cancer patients showed&#xD;
      that four out of eight studies that evaluated bio-physiological outcomes found significant&#xD;
      differences in pulse rate, showing lower heart rate in the VR group compared with the&#xD;
      non-treatment control group. Furthermore, all studies evaluating the efficacy of VR on&#xD;
      different psychological variables found a significant improvement following treatment. In&#xD;
      addition, there have been studies of virtual reality in women receiving chemotherapy, older&#xD;
      women with breast cancer receiving chemotherapy, adults with breast, colon and lung cancer&#xD;
      receiving chemotherapy, and older children receiving chemotherapy. Results of these&#xD;
      interventions have been positive, with patients reporting to decreased psychological&#xD;
      distress, perception that treatment times were shortened and a belief that treatment with&#xD;
      virtual reality was better than chemotherapy alone. Importantly, patients generally did not&#xD;
      report cyber sickness (i.e., nausea and discomfort that can last for hours after&#xD;
      participating in VR applications) and the VR intervention was easy to implement.&#xD;
&#xD;
      Previous findings in the field of body-mind treatments, and specifically VR as a treatment&#xD;
      for women with breast cancer, have led to the current study, which aimed to evaluate the&#xD;
      Bubble, a new VR-AI way of treatment specifically tailored for improving symptoms associated&#xD;
      with hot flashes in female cancer patients. As previous findings in the field showed the&#xD;
      advantages of VR, CBT and mindfulness as treatments for women with cancer or for women who&#xD;
      suffer from hot flashes, they are not specific to hot flashes caused by cancer nor not&#xD;
      combining the three methods together. In this study we are trying to understand the effect of&#xD;
      CBT and mindfulness treatment when given with a VR technology. Specifically, we tried to&#xD;
      explore the effect of this combined type of treatment on women who suffer from hot flashes&#xD;
      caused by cancer. Furthermore, the current study tries to understand what method work for&#xD;
      whom and hence we recruited younger and older women and didn't focused only on one age group.&#xD;
&#xD;
      This pilot study evaluated the potential of a unique artificial intelligence-virtual reality&#xD;
      intervention called Bubble, to reduce the number and intensity of hot flashes and their&#xD;
      accompanying psychological symptoms in women, aged 28-55, with breast cancer. A repeated&#xD;
      measures design was used to answer the following questions: (1) Is AI-VR an effective&#xD;
      intervention for reducing hot flashes in women with breast cancer? (2) Is AI-VR intervention&#xD;
      decreases the intensity and/or frequency of symptoms associated with hot flashes in women&#xD;
      with breast cancer?&#xD;
&#xD;
      Based on past research, as well as our own pilot data collected from focus groups (detailed&#xD;
      in the procedure section), we hypothesized that the use of Bubble will lead to an improvement&#xD;
      decrease intensity of hot flashes and the psychological symptoms connecting to them (stress,&#xD;
      psychopathology level), as well as improve life and sleep quality.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 1, 2018</start_date>
  <completion_date type="Actual">February 28, 2019</completion_date>
  <primary_completion_date type="Actual">February 28, 2019</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>Demographic and background (disease &amp; treatment-elated) information</measure>
    <time_frame>Through study completion, an average of 1 month</time_frame>
    <description>A form was used to assess demographic information, including birth date, race, education, marital status, employment status, and household income. Women also were asked to record their height and weight, which was used to calculate body mass index. Routine information regarding date of diagnosis, stage of disease, and types and dates of cancer treatments was obtained from medical records</description>
  </primary_outcome>
  <primary_outcome>
    <measure>HFRDIS, The Hot Flash Related Daily Interference Scale</measure>
    <time_frame>Through study completion, an average of 1 month, before the manipulation</time_frame>
    <description>The Hot Flash Related Daily Interference Scale (HFRDIS;Carpenter, 2001) is a 10-item scale measuring the degree to which hot flashes interfere with nine daily activities; the tenth item measures the degree hot flashes interfere with overall quality of life. The HFRDIS was developed to include daily life activities specific to the impact of hot flashes. Participants rate the degree to which hot flashes have interfered with each item during the previous week using a 0 (do not interfere) to 10 (completely interfere) point scale. A total score is computed by summing items. Higher scores indicate higher interference due to hot flashes and thus, greater impact on quality of life.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>HFRDIS, The Hot Flash Related Daily Interference Scale</measure>
    <time_frame>Through study completion, an average of 1 month, after the manipulation</time_frame>
    <description>The Hot Flash Related Daily Interference Scale (HFRDIS;Carpenter, 2001) is a 10-item scale measuring the degree to which hot flashes interfere with nine daily activities; the tenth item measures the degree hot flashes interfere with overall quality of life. The HFRDIS was developed to include daily life activities specific to the impact of hot flashes. Participants rate the degree to which hot flashes have interfered with each item during the previous week using a 0 (do not interfere) to 10 (completely interfere) point scale. A total score is computed by summing items. Higher scores indicate higher interference due to hot flashes and thus, greater impact on quality of life.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>HFRS, The Hot Flash Rating Scale</measure>
    <time_frame>Through study completion, an average of 1 month, before the manipulation</time_frame>
    <description>measures the frequency and intensity of hot flashes and night sweats per day and per week. It also estimates chronicity and average duration of the hot flashes, as well as provides rating on three separate ten-point scales (1/10 being the least and 10/10 being the most) for the amount of distress, the extent to which HFs interfered with daily life and the degree to which HFs were a problem in patients' lives. A higher score indicates more HF per day.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>HFRS, The Hot Flash Rating Scale</measure>
    <time_frame>Through study completion, an average of 1 month, after the manipulation</time_frame>
    <description>measures the frequency and intensity of hot flashes and night sweats per day and per week. It also estimates chronicity and average duration of the hot flashes, as well as provides rating on three separate ten-point scales (1/10 being the least and 10/10 being the most) for the amount of distress, the extent to which HFs interfered with daily life and the degree to which HFs were a problem in patients' lives. A higher score indicates more HF per day.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PSS, The Perceived Stress Scale</measure>
    <time_frame>Through study completion, an average of 1 month, before the manipulation</time_frame>
    <description>a self-reported questionnaire that was designed to measure the degree to which situations in one's life over the past week are appraised as unpredictable, uncontrollable and overwhelming. It posits that people appraise potentially-threatening or challenging events in relation to their available coping resources. Items are rated on a Likert scale ranging from 0 (never) to 4 (very often). A higher score indicates a greater degree of perceived stress.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PSS, The Perceived Stress Scale</measure>
    <time_frame>Through study completion, an average of 1 month, after the manipulation</time_frame>
    <description>a self-reported questionnaire that was designed to measure the degree to which situations in one's life over the past week are appraised as unpredictable, uncontrollable and overwhelming. It posits that people appraise potentially-threatening or challenging events in relation to their available coping resources. Items are rated on a Likert scale ranging from 0 (never) to 4 (very often). A higher score indicates a greater degree of perceived stress.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>K10, The Kessler Psychological Distress Scale</measure>
    <time_frame>Through study completion, an average of 1 month, before the manipulation</time_frame>
    <description>10-item measure of psychological distress in the past month, which reliably predicts the presence of a current depressive or anxiety disorder at a cut-off score of 17. The K10 is a 10-item questionnaire rated on a five-point Likert-type scale (from &quot;none of the time&quot; = 1 to &quot;all of the time&quot; = 5). A higher score indicates a greater degree of distress.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>K10, The Kessler Psychological Distress Scale</measure>
    <time_frame>Through study completion, an average of 1 month, after the manipulation</time_frame>
    <description>10-item measure of psychological distress in the past month, which reliably predicts the presence of a current depressive or anxiety disorder at a cut-off score of 17. The K10 is a 10-item questionnaire rated on a five-point Likert-type scale (from &quot;none of the time&quot; = 1 to &quot;all of the time&quot; = 5). A higher score indicates a greater degree of distress.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>B-IPQ, The Brief Illness Perception Questionnaire</measure>
    <time_frame>Through study completion, an average of 1 month, before the manipulation</time_frame>
    <description>is designed to provide simple and rapid assessment of illness perceptions, using single items on a scale from 1-10 to assess each item including; perceived consequences, timeline (acute vs chronic), amount of perceived personal control, treatment control, identity (symptoms), concern about the illness, coherence of the illness and emotional representation of the illness.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>B-IPQ, The Brief Illness Perception Questionnaire</measure>
    <time_frame>Through study completion, an average of 1 month, after the manipulation</time_frame>
    <description>is designed to provide simple and rapid assessment of illness perceptions, using single items on a scale from 1-10 to assess each item including; perceived consequences, timeline (acute vs chronic), amount of perceived personal control, treatment control, identity (symptoms), concern about the illness, coherence of the illness and emotional representation of the illness.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PSQI, The Pittsburgh Sleep Quality Index</measure>
    <time_frame>Through study completion, an average of 1 month, before the manipulation</time_frame>
    <description>a retrospective self-report questionnaire that measures sleep quality over the previous month. Seven clinically derived domains of sleep difficulties (sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction) are assessed. The PSQI global score allowed discriminating between healthy controls and patients, and between groups of patients affected by different pathologies. Results also indicated that the best cut-off score (differentiating &quot;good&quot; from &quot;bad&quot; sleepers) is 5.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PSQI, The Pittsburgh Sleep Quality Index</measure>
    <time_frame>Through study completion, an average of 1 month, after the manipulation</time_frame>
    <description>a retrospective self-report questionnaire that measures sleep quality over the previous month. Seven clinically derived domains of sleep difficulties (sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction) are assessed. The PSQI global score allowed discriminating between healthy controls and patients, and between groups of patients affected by different pathologies. Results also indicated that the best cut-off score (differentiating &quot;good&quot; from &quot;bad&quot; sleepers) is 5.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>WHOQOL-BREF, The World Health Organization Quality of Life Scale</measure>
    <time_frame>Through study completion, an average of 1 month, before the manipulation</time_frame>
    <description>assesses individuals' perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns. The WHOQOL-BREF is a 26-item version of the WHOQOL-100 scale, and as the WHOQOL-100 it includes four domains: physical, psychological, social and environmental QOL and 5-point response scales (5,Very satisfied-1,Very dissatisfied;1,Not at all-5,Extremely; 1,Not at all-5,Completely; and 1,Never-5,Always) and Domain scores are scaled in a positive direction (i.e. higher scores denote higher quality of life).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>WHOQOL-BREF, The World Health Organization Quality of Life Scale</measure>
    <time_frame>Through study completion, an average of 1 month, after the manipulation</time_frame>
    <description>assesses individuals' perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns. The WHOQOL-BREF is a 26-item version of the WHOQOL-100 scale, and as the WHOQOL-100 it includes four domains: physical, psychological, social and environmental QOL and 5-point response scales (5,Very satisfied-1,Very dissatisfied;1,Not at all-5,Extremely; 1,Not at all-5,Completely; and 1,Never-5,Always) and Domain scores are scaled in a positive direction (i.e. higher scores denote higher quality of life).</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">37</enrollment>
  <condition>Hot Flashes</condition>
  <condition>Breast Cancer</condition>
  <arm_group>
    <arm_group_label>research group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Bubble: A New VR-AI Way of Treatment for Hot Flashes</intervention_name>
    <description>Bubble Bubble is a virtual reality (VR) mobile application. Bubble offers a psychological intervention based upon cognitive behavioral therapy (CBT) and mindfulness-based stress reduction (MBSR) protocols. The bubble mobile application offers the intervention in a virtual reality (VR) coaching environment and in a winter wonderland setting called Frosty. Frosty provides both a virtual reality winter wonderland experience as well as guided meditation. The cold, winter-like experience is designed to help patients calm down and feel cooler.</description>
    <arm_group_label>research group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Females between the ages of 18 and 60&#xD;
&#xD;
          -  Having an existing diagnosis of breast or ovarian cancer&#xD;
&#xD;
          -  Receiving standard-of-care chemotherapy, endocrine therapy or estrogen blocking&#xD;
             anti-cancer treatment&#xD;
&#xD;
          -  The woman reported experiencing hot flashes at least once per day for a duration of at&#xD;
             least 7 days prior to the beginning of the study and hot flashes for at least 30 days&#xD;
             prior to the beginning of the study&#xD;
&#xD;
          -  No chronic migraine headaches, seizure disorders, serious vestibular disorders, or&#xD;
             pathological vertigo&#xD;
&#xD;
          -  No serious psychiatric disorders&#xD;
&#xD;
          -  Not pregnant&#xD;
&#xD;
          -  No current substance abuse&#xD;
&#xD;
          -  Not participating in other forms of therapy&#xD;
&#xD;
          -  Not using medical marijuana.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        * women aged 28-55 with breast cancer suffering from hot flashes&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>28 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Bar Ilan University</name>
      <address>
        <city>Ramat Gan</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <link>
    <url>https://doi.org/10.1111/j.1467-842X.2001.tb00310.x</url>
    <description>Andrews, G., &amp; Slade, T. (2001). Interpreting scores on the Kessler Psychological Distress Scale (K10). Australian and New Zealand Journal of Public Health, 25(6), 494-497.</description>
  </link>
  <link>
    <url>https://doi.org/10.1016/S0378-5122(99)00081-X</url>
    <description>Blumel, J. E., Castelo-Branco, C., Binfa, L., Gramegna, G., Tacla, X., Aracena, B., … Sanjuan, A. (2000). Quality of life after the menopause: A population study. Maturitas, 34(1), 17-23.</description>
  </link>
  <link>
    <url>https://doi.org/10.1016/0165-1781(89)90047-4</url>
    <description>Buysse, D. J., Reynolds, C. F., Monk, T. H., Berman, S. R., &amp; Kupfer, D. J. (1989). The Pittsburgh sleep quality index: A new instrument for psychiatric practice and research. Psychiatry Research, 28(2), 193-213</description>
  </link>
  <link>
    <url>https://doi.org/10.1016/j.jpainsymman.2007.05.014</url>
    <description>Fenlon, D. R., Corner, J. L., &amp; Haviland, J. S. (2008). A Randomized Controlled Trial of Relaxation Training to Reduce Hot Flashes in Women with Primary Breast Cancer. Journal of Pain and Symptom Management, 35(4), 397-405</description>
  </link>
  <link>
    <url>https://doi.org/10.1097/GME.0000000000000933</url>
    <description>Hardy, C. (2017). The Hot Flash Related Daily Interference Scale: Cutoffs, minimally important differences, and a revised short version. Menopause, 24(8), 869-870.</description>
  </link>
  <link>
    <url>https://doi.org/10.1097/gme.0b013e3182578d31</url>
    <description>Kadakia, K. C., Loprinzi, C. L., &amp; Barton, D. L. (2012). Hot flashes: The ongoing search for effective interventions. Menopause: The Journal of The North American Menopause Society, 19(7), 719-721.</description>
  </link>
  <link>
    <url>https://doi.org/10.1016/j.anr.2012.08.004</url>
    <description>Lee, E.-H. (2012). Review of the Psychometric Evidence of the Perceived Stress Scale. Asian Nursing Research, 6(4), 121-127.</description>
  </link>
  <link>
    <url>https://doi.org/10.1016/j.ejon.2009.01.003</url>
    <description>Nilsson, S., Finnström, B., Kokinsky, E., &amp; Enskär, K. (2009). The use of Virtual Reality for needle-related procedural pain and distress in children and adolescents in a paediatric oncology unit. European Journal of Oncology Nursing, 13(2), 102-109</description>
  </link>
  <link>
    <url>https://doi.org/10.1089/109493103322011605</url>
    <description>Schneider, Susan M., Ellis, M., Coombs, W. T., Shonkwiler, E. L., &amp; Folsom, L. C. (2003). Virtual Reality Intervention for Older Women with Breast Cancer. CyberPsychology &amp; Behavior, 6(3), 301-307.</description>
  </link>
  <link>
    <url>https://doi.org/10.1188/07.ONF.39-46</url>
    <description>Schneider, Susan M., &amp; Hood, L. E. (2007). Virtual Reality: A Distraction Intervention for Chemotherapy. Oncology Nursing Forum, 34(1), 39-46</description>
  </link>
  <link>
    <url>https://doi.org/10.1188/04.ONF.81-88</url>
    <description>Schneider, Susan M., Prince-Paul, M., JoAllen, M., Silverman, P., &amp; Talaba, D. (2004). Virtual Reality as a Distraction Intervention for Women Receiving Chemotherapy. Oncology Nursing Forum, 31(1), 81-88.</description>
  </link>
  <link>
    <url>https://doi.org/10.1023/B:QURE.0000018486.91360.00</url>
    <description>Skevington, S. M., Lotfy, M., &amp; O'Connell, K. A. (2004). The World Health Organization's WHOQOL-BREF quality of life assessment: Psychometric properties and results of the international field trial.</description>
  </link>
  <link>
    <url>https://doi.org/10.1016/S0140-6736(02)11774-0</url>
    <description>Stearns, V., Ullmer, L., Lopez, J. F., Smith, Y., Isaacs, C., &amp; Hayes, D. F. (2002). Hot flushes. The Lancet, 360(9348), 1851-1861</description>
  </link>
  <link>
    <url>https://doi.org/10.1007/s10865-005-9036-1</url>
    <description>Tatrow, K., &amp; Montgomery, G. H. (2006). Cognitive Behavioral Therapy Techniques for Distress and Pain in Breast Cancer Patients: A Meta-Analysis. Journal of Behavioral Medicine, 29(1), 17-27</description>
  </link>
  <link>
    <url>https://doi.org/10.1016/0277-9536(95)00112-K</url>
    <description>The World Health Organization quality of life assessment (WHOQOL): Position paper from the World Health Organization. (1995). Social Science &amp; Medicine, 41(10), 1403-1409.</description>
  </link>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>May 15, 2020</study_first_submitted>
  <study_first_submitted_qc>May 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>January 12, 2022</last_update_submitted>
  <last_update_submitted_qc>January 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 27, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Bar-Ilan University, Israel</investigator_affiliation>
    <investigator_full_name>Danny Horesh</investigator_full_name>
    <investigator_title>Senior lecturer and head of the Trauma and Stress Research Lab at Bar-Ilan University's Department of Psychology</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Hot Flashes</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04414033
org study id: 22012020
nct id: NCT04414033
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study evaluates the potential of a unique artificial intelligence-virtual reality
      intervention called Bubble, to reduce the number and intensity of hot flashes and their
      accompanying psychological symptoms in women, aged 28-55, with breast cancer. A sample of 37
      women with breast cancer were selected to the study. Participants were asked to answer a
      survey before and after using Bubble. The treatment period was 24 days. The findings are
      positive and show that the use of Bubble help to reduce several psychological symptoms
      connected to hot flashes.
Breast cancer is the most common cancer in women and the leading cause of death in women aged
      < 55 years . Hot flashes are experienced by about 52% of perimenopausal women. After breast
      cancer, this may increase to 70%. Hot flash is a subjective sensation of heat that is
      associated with objective signs of cutaneous vasodilatation and a subsequent drop in core
      temperature. The hot flash may be accompanied by physiological symptoms as sweating,
      flashing, palpitations, and night sweat. As well as by psychological symptoms as anxiety,
      irritability, and even panic. Hot flashes and night sweats (HF/NS) affect 65-85% of breast
      cancer survivors and are associated with sleep problems and reduced quality of life.

      It is well known that estrogen largely alleviates vasomotor symptoms, however concerns
      regarding its use in women, with or without breast cancer, has led to extensive research
      efforts to find well tolerated and efficient nonhormonal interventions. Postmenopausal women
      and breast cancer survivors experience psychological, spiritual, sleep, and cognitive
      dysfunction beyond what could be attributable to vasomotor symptoms alone. Therefore, an
      integrative intervention that can address multiple symptoms is an important patient-centric
      strategy.

      These days a growing body of research has been dedicated to mind-body interventions. These
      interventions include yoga, hypnosis, relaxation-training/paced respiration,
      mindfulness-based stress reduction (MBSR), and cognitive behavioral therapy (CBT). In
      practice, a previous study demonstrated that distressing or problematic hot flashes were
      predicted by depression, anxiety, and low self-image, but not by the frequency of the hot
      flashes. Therefore, women with the same amount of hot flashes may have different and diverse
      emotional responses to their hot flashes. This psychosocial aspect plays a role in the
      distress or can be related to the symptom as well as to the person's will to do something
      about his situation. Cognitive behavioral therapy has a long and well documented history of
      efficacy related to distress, sleep, and psychological aspects of coping with many of life's
      challenges. A study showed that a brief, mindfulness-based intervention demonstrated
      preliminary short-term efficacy in reducing stress, behavioral symptoms, and proinflammatory
      signaling in younger breast cancer survivors. Also, research indicated that relaxation
      training reduced the incidence and severity of hot flashes and the distress caused by the
      flashes in women with primary breast cancer compered to control group.

      Virtual reality (VR) is a computer technology that uses virtual reality headsets or
      multi-projected environments, sometimes in combination with physical environments or props,
      to generate realistic images, sounds and other sensations that simulate a user's physical
      presence in a virtual or imaginary environment. Today there are two main categories of VR,
      immersive and non-immersive. Immersion or presence can be regarded as a variable that can
      influence the effects on the attention of users. Full immersion is reached by a head mounted
      display, which blocks the users' view of the real world and presents patients with a view of
      a computer-generated world instead. This technology may offer subjects a safe environment.

      A review of 19 studies reporting the use of VR in therapies related to cancer patients showed
      that four out of eight studies that evaluated bio-physiological outcomes found significant
      differences in pulse rate, showing lower heart rate in the VR group compared with the
      non-treatment control group. Furthermore, all studies evaluating the efficacy of VR on
      different psychological variables found a significant improvement following treatment. In
      addition, there have been studies of virtual reality in women receiving chemotherapy, older
      women with breast cancer receiving chemotherapy, adults with breast, colon and lung cancer
      receiving chemotherapy, and older children receiving chemotherapy. Results of these
      interventions have been positive, with patients reporting to decreased psychological
      distress, perception that treatment times were shortened and a belief that treatment with
      virtual reality was better than chemotherapy alone. Importantly, patients generally did not
      report cyber sickness (i.e., nausea and discomfort that can last for hours after
      participating in VR applications) and the VR intervention was easy to implement.

      Previous findings in the field of body-mind treatments, and specifically VR as a treatment
      for women with breast cancer, have led to the current study, which aimed to evaluate the
      Bubble, a new VR-AI way of treatment specifically tailored for improving symptoms associated
      with hot flashes in female cancer patients. As previous findings in the field showed the
      advantages of VR, CBT and mindfulness as treatments for women with cancer or for women who
      suffer from hot flashes, they are not specific to hot flashes caused by cancer nor not
      combining the three methods together. In this study we are trying to understand the effect of
      CBT and mindfulness treatment when given with a VR technology. Specifically, we tried to
      explore the effect of this combined type of treatment on women who suffer from hot flashes
      caused by cancer. Furthermore, the current study tries to understand what method work for
      whom and hence we recruited younger and older women and didn't focused only on one age group.

      This pilot study evaluated the potential of a unique artificial intelligence-virtual reality
      intervention called Bubble, to reduce the number and intensity of hot flashes and their
      accompanying psychological symptoms in women, aged 28-55, with breast cancer. A repeated
      measures design was used to answer the following questions: (1) Is AI-VR an effective
      intervention for reducing hot flashes in women with breast cancer? (2) Is AI-VR intervention
      decreases the intensity and/or frequency of symptoms associated with hot flashes in women
      with breast cancer?

      Based on past research, as well as our own pilot data collected from focus groups (detailed
      in the procedure section), we hypothesized that the use of Bubble will lead to an improvement
      decrease intensity of hot flashes and the psychological symptoms connecting to them (stress,
      psychopathology level), as well as improve life and sleep quality.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Demographic and background (disease & treatment-elated) information
time frame: Through study completion, an average of 1 month
description: A form was used to assess demographic information, including birth date, race, education, marital status, employment status, and household income. Women also were asked to record their height and weight, which was used to calculate body mass index. Routine information regarding date of diagnosis, stage of disease, and types and dates of cancer treatments was obtained from medical records
measure: HFRDIS, The Hot Flash Related Daily Interference Scale
time frame: Through study completion, an average of 1 month, before the manipulation
description: The Hot Flash Related Daily Interference Scale (HFRDIS;Carpenter, 2001) is a 10-item scale measuring the degree to which hot flashes interfere with nine daily activities; the tenth item measures the degree hot flashes interfere with overall quality of life. The HFRDIS was developed to include daily life activities specific to the impact of hot flashes. Participants rate the degree to which hot flashes have interfered with each item during the previous week using a 0 (do not interfere) to 10 (completely interfere) point scale. A total score is computed by summing items. Higher scores indicate higher interference due to hot flashes and thus, greater impact on quality of life.
measure: HFRDIS, The Hot Flash Related Daily Interference Scale
time frame: Through study completion, an average of 1 month, after the manipulation
description: The Hot Flash Related Daily Interference Scale (HFRDIS;Carpenter, 2001) is a 10-item scale measuring the degree to which hot flashes interfere with nine daily activities; the tenth item measures the degree hot flashes interfere with overall quality of life. The HFRDIS was developed to include daily life activities specific to the impact of hot flashes. Participants rate the degree to which hot flashes have interfered with each item during the previous week using a 0 (do not interfere) to 10 (completely interfere) point scale. A total score is computed by summing items. Higher scores indicate higher interference due to hot flashes and thus, greater impact on quality of life.
measure: HFRS, The Hot Flash Rating Scale
time frame: Through study completion, an average of 1 month, before the manipulation
description: measures the frequency and intensity of hot flashes and night sweats per day and per week. It also estimates chronicity and average duration of the hot flashes, as well as provides rating on three separate ten-point scales (1/10 being the least and 10/10 being the most) for the amount of distress, the extent to which HFs interfered with daily life and the degree to which HFs were a problem in patients' lives. A higher score indicates more HF per day.
measure: HFRS, The Hot Flash Rating Scale
time frame: Through study completion, an average of 1 month, after the manipulation
description: measures the frequency and intensity of hot flashes and night sweats per day and per week. It also estimates chronicity and average duration of the hot flashes, as well as provides rating on three separate ten-point scales (1/10 being the least and 10/10 being the most) for the amount of distress, the extent to which HFs interfered with daily life and the degree to which HFs were a problem in patients' lives. A higher score indicates more HF per day.
measure: PSS, The Perceived Stress Scale
time frame: Through study completion, an average of 1 month, before the manipulation
description: a self-reported questionnaire that was designed to measure the degree to which situations in one's life over the past week are appraised as unpredictable, uncontrollable and overwhelming. It posits that people appraise potentially-threatening or challenging events in relation to their available coping resources. Items are rated on a Likert scale ranging from 0 (never) to 4 (very often). A higher score indicates a greater degree of perceived stress.
measure: PSS, The Perceived Stress Scale
time frame: Through study completion, an average of 1 month, after the manipulation
description: a self-reported questionnaire that was designed to measure the degree to which situations in one's life over the past week are appraised as unpredictable, uncontrollable and overwhelming. It posits that people appraise potentially-threatening or challenging events in relation to their available coping resources. Items are rated on a Likert scale ranging from 0 (never) to 4 (very often). A higher score indicates a greater degree of perceived stress.
measure: K10, The Kessler Psychological Distress Scale
time frame: Through study completion, an average of 1 month, before the manipulation
description: 10-item measure of psychological distress in the past month, which reliably predicts the presence of a current depressive or anxiety disorder at a cut-off score of 17. The K10 is a 10-item questionnaire rated on a five-point Likert-type scale (from "none of the time" = 1 to "all of the time" = 5). A higher score indicates a greater degree of distress.
measure: K10, The Kessler Psychological Distress Scale
time frame: Through study completion, an average of 1 month, after the manipulation
description: 10-item measure of psychological distress in the past month, which reliably predicts the presence of a current depressive or anxiety disorder at a cut-off score of 17. The K10 is a 10-item questionnaire rated on a five-point Likert-type scale (from "none of the time" = 1 to "all of the time" = 5). A higher score indicates a greater degree of distress.
measure: B-IPQ, The Brief Illness Perception Questionnaire
time frame: Through study completion, an average of 1 month, before the manipulation
description: is designed to provide simple and rapid assessment of illness perceptions, using single items on a scale from 1-10 to assess each item including; perceived consequences, timeline (acute vs chronic), amount of perceived personal control, treatment control, identity (symptoms), concern about the illness, coherence of the illness and emotional representation of the illness.
measure: B-IPQ, The Brief Illness Perception Questionnaire
time frame: Through study completion, an average of 1 month, after the manipulation
description: is designed to provide simple and rapid assessment of illness perceptions, using single items on a scale from 1-10 to assess each item including; perceived consequences, timeline (acute vs chronic), amount of perceived personal control, treatment control, identity (symptoms), concern about the illness, coherence of the illness and emotional representation of the illness.
measure: PSQI, The Pittsburgh Sleep Quality Index
time frame: Through study completion, an average of 1 month, before the manipulation
description: a retrospective self-report questionnaire that measures sleep quality over the previous month. Seven clinically derived domains of sleep difficulties (sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction) are assessed. The PSQI global score allowed discriminating between healthy controls and patients, and between groups of patients affected by different pathologies. Results also indicated that the best cut-off score (differentiating "good" from "bad" sleepers) is 5.
measure: PSQI, The Pittsburgh Sleep Quality Index
time frame: Through study completion, an average of 1 month, after the manipulation
description: a retrospective self-report questionnaire that measures sleep quality over the previous month. Seven clinically derived domains of sleep difficulties (sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction) are assessed. The PSQI global score allowed discriminating between healthy controls and patients, and between groups of patients affected by different pathologies. Results also indicated that the best cut-off score (differentiating "good" from "bad" sleepers) is 5.
measure: WHOQOL-BREF, The World Health Organization Quality of Life Scale
time frame: Through study completion, an average of 1 month, before the manipulation
description: assesses individuals' perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns. The WHOQOL-BREF is a 26-item version of the WHOQOL-100 scale, and as the WHOQOL-100 it includes four domains: physical, psychological, social and environmental QOL and 5-point response scales (5,Very satisfied-1,Very dissatisfied;1,Not at all-5,Extremely; 1,Not at all-5,Completely; and 1,Never-5,Always) and Domain scores are scaled in a positive direction (i.e. higher scores denote higher quality of life).
measure: WHOQOL-BREF, The World Health Organization Quality of Life Scale
time frame: Through study completion, an average of 1 month, after the manipulation
description: assesses individuals' perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns. The WHOQOL-BREF is a 26-item version of the WHOQOL-100 scale, and as the WHOQOL-100 it includes four domains: physical, psychological, social and environmental QOL and 5-point response scales (5,Very satisfied-1,Very dissatisfied;1,Not at all-5,Extremely; 1,Not at all-5,Completely; and 1,Never-5,Always) and Domain scores are scaled in a positive direction (i.e. higher scores denote higher quality of life).
arm group label: research group
arm group type: Experimental
intervention type: Device
intervention name: Bubble: A New VR-AI Way of Treatment for Hot Flashes
description: Bubble Bubble is a virtual reality (VR) mobile application. Bubble offers a psychological intervention based upon cognitive behavioral therapy (CBT) and mindfulness-based stress reduction (MBSR) protocols. The bubble mobile application offers the intervention in a virtual reality (VR) coaching environment and in a winter wonderland setting called Frosty. Frosty provides both a virtual reality winter wonderland experience as well as guided meditation. The cold, winter-like experience is designed to help patients calm down and feel cooler.
arm group label: research group
criteria: 
gender: Female
minimum age: 28 Years
maximum age: 55 Years
healthy volunteers: No
facility: 
country: Israel
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url: https://doi.org/10.1016/S0378-5122(99)00081-X
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url: https://doi.org/10.1089/109493103322011605
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url: https://doi.org/10.1188/04.ONF.81-88
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responsible party type: Principal Investigator
investigator affiliation: Bar-Ilan University, Israel
investigator full name: Danny Horesh
investigator title: Senior lecturer and head of the Trauma and Stress Research Lab at Bar-Ilan University's Department of Psychology
mesh term: Breast Neoplasms
mesh term: Hot Flashes