<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/NCT03838523</url>
  </required_header>
  <id_info>
    <org_study_id>1705-100</org_study_id>
    <nct_id>NCT03838523</nct_id>
  </id_info>
  <brief_title>Non-concealed Placebo Treatment for Menopausal Hot Flushes</brief_title>
  <official_title>Non-concealed Placebo Treatment for Menopausal Hot Flushes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universitätsklinikum Hamburg-Eppendorf</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Universitätsklinikum Hamburg-Eppendorf</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>
      It has been long viewed that placebos cannot be administered in accordance with ethical&#xD;
      values because deception is instrumental to the placebo effect. This notion has been shaken&#xD;
      up by studies on open-label placebos, showing that placebos can lead to positive effects even&#xD;
      though their inert nature is disclosed.&#xD;
&#xD;
      Beneficial effects of double-blind placebos were found to be high in hot flush trials.&#xD;
&#xD;
      The objective of the study is to determine whether an open-label placebo (OLP) treatment is&#xD;
      efficacious in alleviating hot flushes and bother among peri- and postmenopausal women.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Beneficial effects of double-blind placebos were found to be high in hot flush trials. Recent&#xD;
      studies demonstrating the efficacy of placebos without concealment provide a possible way to&#xD;
      administer placebos in accordance with ethical and clinical values.&#xD;
&#xD;
      The objective of the study is to determine whether an open-label placebo (OLP) treatment is&#xD;
      efficacious in alleviating hot flushes and bother among peri- and postmenopausal women.&#xD;
&#xD;
      In this assessor-blinded, randomized-controlled trial, women with ≥5 daily moderate to severe&#xD;
      hot flushes of at least moderate bother are assigned 1:1 to a 4-week OLP treatment or no&#xD;
      treatment. Both groups are informed about study objectives including a briefing about the&#xD;
      inert nature of placebo pills, why OLP might be effective and the importance of the control&#xD;
      group. To explore the duration and maintenance of placebo effects, participants in the OLP&#xD;
      group are randomized a second time and divided into two subgroups who either discontinue (OLP&#xD;
      4wk) or continue the OLP treatment (OLP 8wk) for another 4 weeks. All participants receive&#xD;
      three study visits: at enrolment, baseline (1 week later), and at post-treatment. A fourth&#xD;
      study visit is conducted at 8-week follow-up with the two subgroups OLP 4wk and OLP 8wk.&#xD;
      Qualitative interviews about subjective experiences with the OLP treatment are conducted with&#xD;
      n = 8 women.&#xD;
&#xD;
      This trial will contribute to the evaluation of OLP treatments in clinical practice and&#xD;
      further our understanding about the magnitude of placebo effects in hot flush treatments.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 12, 2019</start_date>
  <completion_date type="Actual">March 5, 2020</completion_date>
  <primary_completion_date type="Actual">February 2, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Women with ≥5 daily moderate to severe hot flushes of at least moderate bother are assigned 1:1 to a 4-week OLP treatment or no treatment. To explore the duration and maintenance of placebo effects, participants in the OLP group are randomized a second time and divided into two subgroups who either discontinue (OLP 4wk) or continue the OLP treatment (OLP 8wk) for another 4 weeks.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>Due to the nature of the study, patients and clinicians are aware of group assignment. Assessors are blinded to group assignment of participants. To prevent the breaking of blinding, participants are requested to not communicate their group affiliation when they have questions about the assessments.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Difference in hot flush composite score</measure>
    <time_frame>4 weeks</time_frame>
    <description>The group difference between OLP and no-treatment regarding frequency x severity of hot flushes as assessed by a portable paper diary in which participants record number and severity of hot flushes in realtime</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Bother by hot flushes</measure>
    <time_frame>4 weeks</time_frame>
    <description>The group difference between OLP and no-treatment regarding bother by hot flushes as assessed by the Hot Flush Rating Scale (Hunter &amp; Liao, 1995). A sum score is calculated which ranges from 3 to 30 with higher scores indicating larger bother by hot flushes.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hot flush frequency</measure>
    <time_frame>4 weeks</time_frame>
    <description>The group difference between OLP and no-treatment regarding the frequency of hot flushes as assessed by the diary</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-related quality of life</measure>
    <time_frame>4 weeks</time_frame>
    <description>The group difference between OLP and no-treatment regarding health-related quality of life as assessed by the Women's Health Questionnaire (WHQ; Hunter, 1992; Shin &amp; Shin, 2012). Using the 37-item version of the WHQ, 8 subscales are calculated: Depressed mood, somatic symptoms, memory/concentration, vasomotor symptoms, anxiety/fears, sexual behaviour, sleep problems, and attractiveness. Although part of the questionnaire, we will not analyze the menstrual symptoms scale given that most women in our sample would be post-menopausal. Higher scores indicate better quality of life (e.g., higher scores in sexual behavior indicate that loss of sexual interest and sexual dissatisfaction is not experienced). Scores for each subscale range from 0 (poor health status) to 100 (good health status).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global improvement</measure>
    <time_frame>4 weeks</time_frame>
    <description>The group difference between OLP and no-treatment regarding global improvement as assessed by the Patient Global Impression of Change (Geisser et al. 2010; Guttoso et al. 2003)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of responders at week 4</measure>
    <time_frame>4 weeks</time_frame>
    <description>The group difference between OLP and no-treatment regarding number of responders at week 4 (≥50% in hot flush frequency at 4 weeks from baseline)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Hot Flashes</condition>
  <arm_group>
    <arm_group_label>OLP group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>At baseline, patients are given an explanation about why placebos without deception might be effective.&#xD;
Women allocated to this group receive an 4-week Open Label Placebo treatment. After 4 weeks, they are randomized again to either continue or discontinue the OLP treatment for another 4 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No-treatment group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>At baseline, patients are given an explanation about why placebos without deception might be effective.&#xD;
Women assigned to the no-treatment group do not receive any treatment as part of the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Open Label Placebo</intervention_name>
    <description>See group description</description>
    <arm_group_label>OLP group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  at least 5 moderate or severe hot flushes per day, including night time&#xD;
&#xD;
          -  all hot flushes have at least moderate ratings of bother (sum score ≥ 16 on the bother&#xD;
             subscale of the Hot Flush Rating Scale (HFRS) [41]&#xD;
&#xD;
          -  fluency in German language&#xD;
&#xD;
          -  participants are in menopausal transition (irregularities ≥ 60 days in the past year),&#xD;
             or postmenopausal (cessation of menstruation ≥ 1 year) [42].&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  use of hormonal therapy to treat hot flushes within the last 6 weeks before enrolment&#xD;
&#xD;
          -  use of herbal remedies to treat hot flushes within the last 6 weeks before enrolment&#xD;
&#xD;
          -  intake of selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine&#xD;
             reuptake inhibitors (SNRI) within the last 6 weeks before enrolment&#xD;
&#xD;
          -  previous oophorectomy&#xD;
&#xD;
          -  severe physical or cognitive impairments which would constitute a barrier to give&#xD;
             informed consent&#xD;
&#xD;
          -  severe depression and anxiety (≥ 9 sum score or ≥ 5 depression or anxiety subscore on&#xD;
             the Patient Health Questionnaire-4)&#xD;
&#xD;
          -  medical conditions which might interact with menopausal hot flushes such as untreated&#xD;
             hyperthyroidism, alcohol abuse (excluded when ≥4 on AUDIT-C) and cancer&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yvonne Nestoriuc, Prof. Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universitätsklinikum Hamburg-Eppendorf</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Medical Center Hamburg-Eppendorf</name>
      <address>
        <city>Hamburg</city>
        <zip>20251</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <reference>
    <citation>Hunter MS, Liao KL. A psychological analysis of menopausal hot flushes. Br J Clin Psychol. 1995 Nov;34(4):589-99. doi: 10.1111/j.2044-8260.1995.tb01493.x.</citation>
    <PMID>8563666</PMID>
  </reference>
  <reference>
    <citation>Geisser ME, Clauw DJ, Strand V, Gendreau MR, Palmer R, Williams DA. Contributions of change in clinical status parameters to Patient Global Impression of Change (PGIC) scores among persons with fibromyalgia treated with milnacipran. Pain. 2010 May;149(2):373-378. doi: 10.1016/j.pain.2010.02.043. Epub 2010 Mar 23.</citation>
    <PMID>20332060</PMID>
  </reference>
  <reference>
    <citation>Guttuso T Jr, Kurlan R, McDermott MP, Kieburtz K. Gabapentin's effects on hot flashes in postmenopausal women: a randomized controlled trial. Obstet Gynecol. 2003 Feb;101(2):337-45. doi: 10.1016/s0029-7844(02)02712-6.</citation>
    <PMID>12576259</PMID>
  </reference>
  <reference>
    <citation>Hunter, M. S. The women's health questionnaire: A measure of mid-aged women's perceptions of their emotional and physical health. Psychology &amp; Health, 7(1), 45-54, 1992.</citation>
  </reference>
  <reference>
    <citation>Shin H, Shin HS. Measurement of quality of life in menopausal women: a systematic review. West J Nurs Res. 2012 Jun;34(4):475-503. doi: 10.1177/0193945911402848. Epub 2011 Mar 25.</citation>
    <PMID>21441417</PMID>
  </reference>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>January 29, 2019</study_first_submitted>
  <study_first_submitted_qc>February 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 12, 2019</study_first_posted>
  <last_update_submitted>February 2, 2021</last_update_submitted>
  <last_update_submitted_qc>February 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 3, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universitätsklinikum Hamburg-Eppendorf</investigator_affiliation>
    <investigator_full_name>Yvonne Nestoriuc</investigator_full_name>
    <investigator_title>Clinical Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hot Flashes</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03838523
org study id: 1705-100
nct id: NCT03838523
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
It has been long viewed that placebos cannot be administered in accordance with ethical
      values because deception is instrumental to the placebo effect. This notion has been shaken
      up by studies on open-label placebos, showing that placebos can lead to positive effects even
      though their inert nature is disclosed.

      Beneficial effects of double-blind placebos were found to be high in hot flush trials.

      The objective of the study is to determine whether an open-label placebo (OLP) treatment is
      efficacious in alleviating hot flushes and bother among peri- and postmenopausal women.
Beneficial effects of double-blind placebos were found to be high in hot flush trials. Recent
      studies demonstrating the efficacy of placebos without concealment provide a possible way to
      administer placebos in accordance with ethical and clinical values.

      The objective of the study is to determine whether an open-label placebo (OLP) treatment is
      efficacious in alleviating hot flushes and bother among peri- and postmenopausal women.

      In this assessor-blinded, randomized-controlled trial, women with ≥5 daily moderate to severe
      hot flushes of at least moderate bother are assigned 1:1 to a 4-week OLP treatment or no
      treatment. Both groups are informed about study objectives including a briefing about the
      inert nature of placebo pills, why OLP might be effective and the importance of the control
      group. To explore the duration and maintenance of placebo effects, participants in the OLP
      group are randomized a second time and divided into two subgroups who either discontinue (OLP
      4wk) or continue the OLP treatment (OLP 8wk) for another 4 weeks. All participants receive
      three study visits: at enrolment, baseline (1 week later), and at post-treatment. A fourth
      study visit is conducted at 8-week follow-up with the two subgroups OLP 4wk and OLP 8wk.
      Qualitative interviews about subjective experiences with the OLP treatment are conducted with
      n = 8 women.

      This trial will contribute to the evaluation of OLP treatments in clinical practice and
      further our understanding about the magnitude of placebo effects in hot flush treatments.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Women with ≥5 daily moderate to severe hot flushes of at least moderate bother are assigned 1:1 to a 4-week OLP treatment or no treatment. To explore the duration and maintenance of placebo effects, participants in the OLP group are randomized a second time and divided into two subgroups who either discontinue (OLP 4wk) or continue the OLP treatment (OLP 8wk) for another 4 weeks.
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: Due to the nature of the study, patients and clinicians are aware of group assignment. Assessors are blinded to group assignment of participants. To prevent the breaking of blinding, participants are requested to not communicate their group affiliation when they have questions about the assessments.
measure: Difference in hot flush composite score
time frame: 4 weeks
description: The group difference between OLP and no-treatment regarding frequency x severity of hot flushes as assessed by a portable paper diary in which participants record number and severity of hot flushes in realtime
measure: Bother by hot flushes
time frame: 4 weeks
description: The group difference between OLP and no-treatment regarding bother by hot flushes as assessed by the Hot Flush Rating Scale (Hunter & Liao, 1995). A sum score is calculated which ranges from 3 to 30 with higher scores indicating larger bother by hot flushes.
measure: Hot flush frequency
time frame: 4 weeks
description: The group difference between OLP and no-treatment regarding the frequency of hot flushes as assessed by the diary
measure: Health-related quality of life
time frame: 4 weeks
description: The group difference between OLP and no-treatment regarding health-related quality of life as assessed by the Women's Health Questionnaire (WHQ; Hunter, 1992; Shin & Shin, 2012). Using the 37-item version of the WHQ, 8 subscales are calculated: Depressed mood, somatic symptoms, memory/concentration, vasomotor symptoms, anxiety/fears, sexual behaviour, sleep problems, and attractiveness. Although part of the questionnaire, we will not analyze the menstrual symptoms scale given that most women in our sample would be post-menopausal. Higher scores indicate better quality of life (e.g., higher scores in sexual behavior indicate that loss of sexual interest and sexual dissatisfaction is not experienced). Scores for each subscale range from 0 (poor health status) to 100 (good health status).
measure: Global improvement
time frame: 4 weeks
description: The group difference between OLP and no-treatment regarding global improvement as assessed by the Patient Global Impression of Change (Geisser et al. 2010; Guttoso et al. 2003)
measure: Number of responders at week 4
time frame: 4 weeks
description: The group difference between OLP and no-treatment regarding number of responders at week 4 (≥50% in hot flush frequency at 4 weeks from baseline)
arm group label: OLP group
arm group type: Experimental
description: At baseline, patients are given an explanation about why placebos without deception might be effective.
Women allocated to this group receive an 4-week Open Label Placebo treatment. After 4 weeks, they are randomized again to either continue or discontinue the OLP treatment for another 4 weeks.
arm group label: No-treatment group
arm group type: No Intervention
description: At baseline, patients are given an explanation about why placebos without deception might be effective.
Women assigned to the no-treatment group do not receive any treatment as part of the study.
intervention type: Other
intervention name: Open Label Placebo
description: See group description
arm group label: OLP group
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Yvonne Nestoriuc, Prof. Dr.
role: Principal Investigator
affiliation: Universitätsklinikum Hamburg-Eppendorf
facility: 
country: Germany
citation: Hunter MS, Liao KL. A psychological analysis of menopausal hot flushes. Br J Clin Psychol. 1995 Nov;34(4):589-99. doi: 10.1111/j.2044-8260.1995.tb01493.x.
PMID: 8563666
citation: Geisser ME, Clauw DJ, Strand V, Gendreau MR, Palmer R, Williams DA. Contributions of change in clinical status parameters to Patient Global Impression of Change (PGIC) scores among persons with fibromyalgia treated with milnacipran. Pain. 2010 May;149(2):373-378. doi: 10.1016/j.pain.2010.02.043. Epub 2010 Mar 23.
PMID: 20332060
citation: Guttuso T Jr, Kurlan R, McDermott MP, Kieburtz K. Gabapentin's effects on hot flashes in postmenopausal women: a randomized controlled trial. Obstet Gynecol. 2003 Feb;101(2):337-45. doi: 10.1016/s0029-7844(02)02712-6.
PMID: 12576259
citation: Hunter, M. S. The women's health questionnaire: A measure of mid-aged women's perceptions of their emotional and physical health. Psychology & Health, 7(1), 45-54, 1992.
citation: Shin H, Shin HS. Measurement of quality of life in menopausal women: a systematic review. West J Nurs Res. 2012 Jun;34(4):475-503. doi: 10.1177/0193945911402848. Epub 2011 Mar 25.
PMID: 21441417
responsible party type: Principal Investigator
investigator affiliation: Universitätsklinikum Hamburg-Eppendorf
investigator full name: Yvonne Nestoriuc
investigator title: Clinical Professor
mesh term: Hot Flashes
sharing ipd: No