<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/NCT04480658</url>
  </required_header>
  <id_info>
    <org_study_id>2017-01964</org_study_id>
    <nct_id>NCT04480658</nct_id>
  </id_info>
  <brief_title>Effectiveness of Bryophyllum in Nocturia-Therapy</brief_title>
  <official_title>Effectiveness of Bryophyllum Pinnatum by Patients With Nocturia and Its Effect on Sleep Quality</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Zurich</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Zurich</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Night-time micturition, called nocturia, is a very common problem that unfavourably&#xD;
      influences sleep- and life-qualities. The International Continence Society (ICS) defines&#xD;
      nocturia as micturition once or several times during the night. Nocturia is one of the&#xD;
      cardinal symptoms of overactive bladder (OAB). Persons with nocturia have the intention to&#xD;
      continue sleep after going to the toilet which does not succeed to the same extent, depending&#xD;
      on age.&#xD;
&#xD;
      The natural occurrence of the plant, Bryophyllum pinnatum (BP) which is used in this&#xD;
      observational study origins from Madagascar as well as in tropical Africa, South America and&#xD;
      Asia. In the folk medicine of these countries BP is widely used. BP has a calming,&#xD;
      spasmolytic, anti-inflammatory, pain-relieving, diuretic and cytotoxic effects.&#xD;
&#xD;
      According to previous preclinical and clinical studies the inhibiting effect of BP on&#xD;
      overactive bladder was proven. The pharmacological effect of this plant on uterine smooth&#xD;
      muscle cells, on spontaneous and oxytocin-stimulated contractions, and on detrusor muscle&#xD;
      cells in an in-vitro model of the pig's bladder was shown. Smooth muscle relaxation is not&#xD;
      only required for preventing premature labour but also for symptom's relief of overactive&#xD;
      bladder (OAB). The flavonoid, aglycons and bufadienolides, are components of the pressed&#xD;
      juice of the BP leaves that have comparable effects to the standard drug oxybutynin on&#xD;
      vesical smooth muscle cells.&#xD;
&#xD;
      Since many year BP is used in obstetrics not only as tocolytics but also as a sedative and&#xD;
      sleeping pill.&#xD;
&#xD;
      There are known only few adverse events, such as skin irritation by intravenous application.&#xD;
&#xD;
      The interest in phytotherapeutical drugs for treatment the chronic diseases is very high and&#xD;
      Bryophyllum is also frequently used in Switzerland for hyperactive conditions.&#xD;
&#xD;
      In Switzerland, following the vote on complementary medicine on 17.05.2009, alternative&#xD;
      treatments will be covered by basic health insurance. Definitive inclusion in the catalogue&#xD;
      of benefits will be granted if effectiveness, safety and cost-effectiveness can be&#xD;
      demonstrated.&#xD;
&#xD;
      The potential and side-effect profile of BP, as well as the social interest in research into&#xD;
      alternative methods is the background to the implementation of this observational study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In the therapeutic concept of the treatment of OAB, antimuscarinic drugs play a central role.&#xD;
      Antimuscarinics are known to inhibit the contraction of detrusor muscle (smooth muscle cells)&#xD;
      and block the muscarinic receptor (M2/M3) important for efferent nerve conduction. This&#xD;
      conventional therapy for OAB can have important adverse effects, notably on the&#xD;
      gastrointestinal tract with constipation, on the excretory glands in the sense of&#xD;
      xerostomia/xerophthalmia, on the nerve cells of the brain inhibiting cognitive function and&#xD;
      in the heart muscle cells accelerating the heart rate. Especially elderly people are affected&#xD;
      by these undesirable effects. Because of changes in the receptor profile, the effect of&#xD;
      antimuscarinics and improvement of symptoms might be lowered in elderly people and another&#xD;
      substance with less side effects would be of great interest. No such adverse effects are&#xD;
      reported for B. pinnatum. Until now, there are few data for its use in OAB. Efficacy and&#xD;
      tolerability of B. pinnatum in the treatment of OAB are the major outcome measures of this&#xD;
      clinical trial.&#xD;
&#xD;
        -  50 women are included in this observational study, treated with Bryophyllum pinnatum in&#xD;
           form of the commercially available Bryophyllum tablets into capsules (verum:&#xD;
           2x2capsules/day). Recruitment time is planned from January, 2018 to January 2022.&#xD;
&#xD;
        -  Duration of the drug administration is 3 weeks.&#xD;
&#xD;
        -  Primary endpoint are the reduction of nocturia (measured by filling in a voiding dairy)&#xD;
           and the change of sleep-quality (measured by using Pittsburgh Sleep Quality Index)&#xD;
&#xD;
        -  secondary endpoints are the improvement of quality of life (measured by using the King's&#xD;
           Health Questionnaire and the International Consultation on Incontinence Overactive&#xD;
           Bladder Questionnaire (ICIQ-OAB), two questionnaires, validated for the German language&#xD;
           and for women with incontinence), increase of the micturition volumes and reduction of&#xD;
           urge episodes (measured by the patients and recorded in a voiding dairy) and the&#xD;
           registration of adverse events during the study phase. Ethics committee approval has&#xD;
           been given.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2018</start_date>
  <completion_date type="Actual">January 14, 2022</completion_date>
  <primary_completion_date type="Actual">February 18, 2021</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>Reduction of nocturia frequency</measure>
    <time_frame>4 Weeks</time_frame>
    <description>micturition protocol will be handed over during the baseline visit, it will be filled three days before the second visit in 1 week( therapy-start), follow-up control 3 weeks after medication intake and after the completed medication period ]</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Sleep-Quality.</measure>
    <time_frame>4 Weeks</time_frame>
    <description>Pittsburgh Sleep Quality Index (PSQI; score 0-21) will be handed over during the baseline visit and will be filled three days before the second visit in 1 Week and three days after the therapy-end (after 3 Weeks). The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes of overactive bladder symptoms</measure>
    <time_frame>before the second visit in 1 week, at follow-up control 3 weeks after begin of medication intake and 4 weeks after end of medication intake.</time_frame>
    <description>quality of life is measured by the ICIQ-OAB (score 0-16), a specific questionnaire for OAB</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of Bryophyllum: adverse events</measure>
    <time_frame>4 weeks</time_frame>
    <description>during medication intake at 1 week and 3 weeks after start of medication intake, measured by a personal adverse event protocol</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Daytime sleepiness</measure>
    <time_frame>before the second visit in 1 week, at follow-up control 3 weeks after begin of medication intake and 4 weeks after end of medication intake.</time_frame>
    <description>quality of life is measured by Epworth Sleepiness Scale Questionnaire (score 0-24)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Nocturia</condition>
  <condition>Sleep Disorder</condition>
  <arm_group>
    <arm_group_label>Bryophyllum pinnatum</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Bryophyllum pinnatum (BP) muscle relaxing substance</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bryophyllum pinnatum 50 %, tablets into capsules (verum: 2x2capsules/day)</intervention_name>
    <description>Bryophyllum is administered for 3 weeks. Bryophyllum is given in form of capsules, 350mg per capsule, 0-0-2-2/d: 2 capsules 30min. before supper,2 capsules before going to bed.&#xD;
Other Names:&#xD;
Bryophyllum pinnatum/Kalanchoe</description>
    <arm_group_label>Bryophyllum pinnatum</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Nocturia ≥2 Mal per a night&#xD;
&#xD;
          -  Overactive bladder (&gt;8 Mictions/day)&#xD;
&#xD;
          -  Age &gt; 18 Years&#xD;
&#xD;
          -  local or systemic Therapy with Estrogen, if the therapy dates &gt;4 Weeks before&#xD;
             study-start.&#xD;
&#xD;
          -  prior incontinence operation (if the operation dates back more than 6 months)&#xD;
&#xD;
          -  german speaking Patients and a given informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Intolerance against a substance or a compound&#xD;
&#xD;
          -  participation in an other study 4 weeks prior to inclusion&#xD;
&#xD;
          -  urinary tract infection&#xD;
&#xD;
          -  drug abuse&#xD;
&#xD;
          -  bladder affecting drugs like anticholinergics, diuretics, muscle relaxing medicaments&#xD;
             and phytotherapeutics&#xD;
&#xD;
          -  lactose intolerance&#xD;
&#xD;
          -  Pregnant and lactating women&#xD;
&#xD;
          -  Incompliance of Patient&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Hospital, Clinic for Gynecology</name>
      <address>
        <city>Zurich</city>
        <zip>8091</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>July 13, 2020</study_first_submitted>
  <study_first_submitted_qc>July 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 21, 2020</study_first_posted>
  <last_update_submitted>January 16, 2022</last_update_submitted>
  <last_update_submitted_qc>January 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 19, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sleep Wake Disorders</mesh_term>
    <mesh_term>Nocturia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
  </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/NCT04480658
org study id: 2017-01964
nct id: NCT04480658
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Night-time micturition, called nocturia, is a very common problem that unfavourably
      influences sleep- and life-qualities. The International Continence Society (ICS) defines
      nocturia as micturition once or several times during the night. Nocturia is one of the
      cardinal symptoms of overactive bladder (OAB). Persons with nocturia have the intention to
      continue sleep after going to the toilet which does not succeed to the same extent, depending
      on age.

      The natural occurrence of the plant, Bryophyllum pinnatum (BP) which is used in this
      observational study origins from Madagascar as well as in tropical Africa, South America and
      Asia. In the folk medicine of these countries BP is widely used. BP has a calming,
      spasmolytic, anti-inflammatory, pain-relieving, diuretic and cytotoxic effects.

      According to previous preclinical and clinical studies the inhibiting effect of BP on
      overactive bladder was proven. The pharmacological effect of this plant on uterine smooth
      muscle cells, on spontaneous and oxytocin-stimulated contractions, and on detrusor muscle
      cells in an in-vitro model of the pig's bladder was shown. Smooth muscle relaxation is not
      only required for preventing premature labour but also for symptom's relief of overactive
      bladder (OAB). The flavonoid, aglycons and bufadienolides, are components of the pressed
      juice of the BP leaves that have comparable effects to the standard drug oxybutynin on
      vesical smooth muscle cells.

      Since many year BP is used in obstetrics not only as tocolytics but also as a sedative and
      sleeping pill.

      There are known only few adverse events, such as skin irritation by intravenous application.

      The interest in phytotherapeutical drugs for treatment the chronic diseases is very high and
      Bryophyllum is also frequently used in Switzerland for hyperactive conditions.

      In Switzerland, following the vote on complementary medicine on 17.05.2009, alternative
      treatments will be covered by basic health insurance. Definitive inclusion in the catalogue
      of benefits will be granted if effectiveness, safety and cost-effectiveness can be
      demonstrated.

      The potential and side-effect profile of BP, as well as the social interest in research into
      alternative methods is the background to the implementation of this observational study.
In the therapeutic concept of the treatment of OAB, antimuscarinic drugs play a central role.
      Antimuscarinics are known to inhibit the contraction of detrusor muscle (smooth muscle cells)
      and block the muscarinic receptor (M2/M3) important for efferent nerve conduction. This
      conventional therapy for OAB can have important adverse effects, notably on the
      gastrointestinal tract with constipation, on the excretory glands in the sense of
      xerostomia/xerophthalmia, on the nerve cells of the brain inhibiting cognitive function and
      in the heart muscle cells accelerating the heart rate. Especially elderly people are affected
      by these undesirable effects. Because of changes in the receptor profile, the effect of
      antimuscarinics and improvement of symptoms might be lowered in elderly people and another
      substance with less side effects would be of great interest. No such adverse effects are
      reported for B. pinnatum. Until now, there are few data for its use in OAB. Efficacy and
      tolerability of B. pinnatum in the treatment of OAB are the major outcome measures of this
      clinical trial.

        -  50 women are included in this observational study, treated with Bryophyllum pinnatum in
           form of the commercially available Bryophyllum tablets into capsules (verum:
           2x2capsules/day). Recruitment time is planned from January, 2018 to January 2022.

        -  Duration of the drug administration is 3 weeks.

        -  Primary endpoint are the reduction of nocturia (measured by filling in a voiding dairy)
           and the change of sleep-quality (measured by using Pittsburgh Sleep Quality Index)

        -  secondary endpoints are the improvement of quality of life (measured by using the King's
           Health Questionnaire and the International Consultation on Incontinence Overactive
           Bladder Questionnaire (ICIQ-OAB), two questionnaires, validated for the German language
           and for women with incontinence), increase of the micturition volumes and reduction of
           urge episodes (measured by the patients and recorded in a voiding dairy) and the
           registration of adverse events during the study phase. Ethics committee approval has
           been given.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Reduction of nocturia frequency
time frame: 4 Weeks
description: micturition protocol will be handed over during the baseline visit, it will be filled three days before the second visit in 1 week( therapy-start), follow-up control 3 weeks after medication intake and after the completed medication period ]
measure: Sleep-Quality.
time frame: 4 Weeks
description: Pittsburgh Sleep Quality Index (PSQI; score 0-21) will be handed over during the baseline visit and will be filled three days before the second visit in 1 Week and three days after the therapy-end (after 3 Weeks). The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality.
measure: Changes of overactive bladder symptoms
time frame: before the second visit in 1 week, at follow-up control 3 weeks after begin of medication intake and 4 weeks after end of medication intake.
description: quality of life is measured by the ICIQ-OAB (score 0-16), a specific questionnaire for OAB
measure: Safety of Bryophyllum: adverse events
time frame: 4 weeks
description: during medication intake at 1 week and 3 weeks after start of medication intake, measured by a personal adverse event protocol
measure: Daytime sleepiness
time frame: before the second visit in 1 week, at follow-up control 3 weeks after begin of medication intake and 4 weeks after end of medication intake.
description: quality of life is measured by Epworth Sleepiness Scale Questionnaire (score 0-24)
arm group label: Bryophyllum pinnatum
arm group type: Experimental
description: Bryophyllum pinnatum (BP) muscle relaxing substance
intervention type: Drug
intervention name: Bryophyllum pinnatum 50 %, tablets into capsules (verum: 2x2capsules/day)
description: Bryophyllum is administered for 3 weeks. Bryophyllum is given in form of capsules, 350mg per capsule, 0-0-2-2/d: 2 capsules 30min. before supper,2 capsules before going to bed.
Other Names:
Bryophyllum pinnatum/Kalanchoe
arm group label: Bryophyllum pinnatum
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Switzerland
responsible party type: Sponsor
mesh term: Sleep Wake Disorders
mesh term: Nocturia
sharing ipd: Yes
ipd info type: Clinical Study Report (CSR)