<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/NCT02258711</url>
  </required_header>
  <id_info>
    <org_study_id>HCPPFR02062014</org_study_id>
    <nct_id>NCT02258711</nct_id>
  </id_info>
  <brief_title>Self-Monitoring and Psychoeducation in Bipolar Patients With a Smart-phone Application</brief_title>
  <acronym>SIMPLE</acronym>
  <official_title>SIgns and Symptoms Self-Monitoring and Psychoeducation in bipoLar Patients With a Smart-phonE Application (SIMPLE)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital Clinic of Barcelona</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Institut d'Investigacions Biomèdiques August Pi i Sunyer</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Institut Hospital del Mar d'Investigacions Mèdiques (IMIM)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Centro de Investigación Biomédica en Red de Salud Mental</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sodep S.A.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hospital Clinic of Barcelona</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Bipolar disorder is a frequent condition in the general population with a high&#xD;
      morbimortality, which consists in dysfunctional temporal fluctuations between different mood&#xD;
      phases ranging from depression to manic episodes with frequent subsyndromal symptoms between&#xD;
      them. Usually during these phases, the subjects have a lack of insight about the diagnosis&#xD;
      and symptoms. Besides the pharmacological treatment, additional psychological interventions&#xD;
      have shown to improve the long-term outcome of the disorder, yet taking into account the&#xD;
      limited resources currently available, its general implementation is still difficult and&#xD;
      costly. Among these interventions, group psychoeducational programs have proved to be&#xD;
      cost-effective in helping patients recognize early signs and symptoms in order to prevent&#xD;
      full blown episodes which very usually are associated with a high morbidity and hospital&#xD;
      admissions.&#xD;
&#xD;
      On the other hand, numerous projects have tested the potential benefits of new technologies&#xD;
      such internet in the treatment of bipolar and psychotic disorders patients using either&#xD;
      online signs and symptoms monitoring or web-based psychoeducational programs, yet to the&#xD;
      investigators knowledge, none of them have integrated both approaches in one single&#xD;
      intervention.&#xD;
&#xD;
      The hypothesis that, combining both interventions (signs and symptoms monitoring along with&#xD;
      psychoeducational contents) in a single smart-phone application will prove to be at least&#xD;
      equal or superior in terms of efficacy comparing to the standard treatment, seems promising,&#xD;
      given the fact that both approaches have independently demonstrated their efficacy in the&#xD;
      same population. This could extend the range of the patients in whom this kind of additional&#xD;
      interventions could be implemented; preventing relapses, suicide attempts, consultations and&#xD;
      hospitalizations at a much lower cost.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The main aim of this study is to develop and clinically validate a smart-phone application to&#xD;
      monitor symptoms and signs in stable bipolar patients, offering also customized embedded&#xD;
      psycho-education contents and empower the self-management of their disorder to avoid relapses&#xD;
      and hospitalizations. Secondary objectives will be to explore other clinical benefits among&#xD;
      the smart-phone application users such as biological rhythms, manic/hypomanic and depressive&#xD;
      symptoms, quality of life, suicide attempts, pharmacological treatment changes as well as&#xD;
      healthcare resource consumption (outpatient and emergency room consultations) in order to&#xD;
      evaluate its cost-efficiency compared to current standard interventions.&#xD;
&#xD;
      The study will include stable bipolar patients (YMRS ≤ 8, HDRS ≤ 6 for at least one month&#xD;
      prior to study entry) who have experienced at least one hypomanic, manic or depressive&#xD;
      relapse during the 12 months prior to study entry. This will be carried out in three&#xD;
      different but complementary phases in order to fully include patients and therapist's&#xD;
      preferences. Along the process, confidential information and data handling will be tested to&#xD;
      ensure privacy and confidentiality are warranted. In this regard, an anonymized user name and&#xD;
      password will be given to the patients who will never have to reveal their real identity to&#xD;
      access the application during the study.&#xD;
&#xD;
        -  First phase: During the first three months a feasibility study will be conducted&#xD;
           evaluating the use, reliability and satisfaction monitoring symptoms (subjective&#xD;
           information) using a smart-phone with the SIMPLe 1.0 application installed. The&#xD;
           intervention will be consecutively offered to 30 stable adults (&gt;18 years) fulfilling&#xD;
           inclusion criteria. The patient will have to read and agree with the terms and sign an&#xD;
           informed consent in order to participate. Sociodemographic data and standardized&#xD;
           clinical as well as functional assessments will be administered at baseline, at the&#xD;
           first, second and third month of the study. The assessments will include present manic&#xD;
           symptoms using the Young Mania Rating Scale (YMRS), depressive symptoms using the&#xD;
           Hamilton depression Rating Scale (HDRS), biological rhythms using the biological rhythms&#xD;
           interview of assessment in neuropsychiatry (BRIAN), quality of life measured by World&#xD;
           Health Organization quality of life assessment (WHOQOL-BREF) and treatment adherence&#xD;
           using the Medication Adherence Rating Scale (MARS). A smart-phone device with the SIMPLe&#xD;
           1.0 application pre-installed, will be given to the participants for free during the&#xD;
           study with the mandatory condition that it has to be their main mobile-phone during the&#xD;
           next 3 months. In the case the patient accepts to participate but doesn´t want to switch&#xD;
           from his/her current smart-phone, he/she will be offered the possibility to download the&#xD;
           SIMPLe 1.0 application from the App Store and a username and password will be given to&#xD;
           use it. The SIMPLe 1.0 application will ask the user by customizable automatic reminder&#xD;
           notifications to answer daily and weekly questionnaires based on DSM-5 (Diagnostic and&#xD;
           Statistical Manual of Mental Disorders, 5th edition) criteria for a manic, hypomanic,&#xD;
           mixed or depressive episode. The use frequency will be measured by the daily and weekly&#xD;
           questionnaires answered which will be registered online. At the same time they will&#xD;
           receive through the application daily customized psychoeducative messages based on the&#xD;
           information collected by the application. Feasibility and satisfaction will be assessed&#xD;
           with the application usage log data and an electronic survey, while the app reliability&#xD;
           to correctly asses the patients mood states will be analyzed comparing the clinical&#xD;
           assessments and the information collected by the application.&#xD;
&#xD;
        -  Second phase: Individual personal interviews with each SIMPLe 1.0 user will also collect&#xD;
           qualitative information about the application and suggestions. Taking into consideration&#xD;
           the information collected from participants in the first phase, the application will be&#xD;
           adapted and improved with the addition of objective information (signs) monitoring&#xD;
           modules using mobile usage parameters and the built-in sensors. Focus groups will be&#xD;
           held with participants, psychiatrists and psychologists to better fit their needs and&#xD;
           incorporate suggestions.&#xD;
&#xD;
        -  Third phase: A randomized controlled trial taking into consideration a significance&#xD;
           level of 0.05, power of 0.8 and a minimal detectable difference of 0.5 and an expected&#xD;
           drop-out of 15%, will be carried out with two arms of 74 patients each, as follows:&#xD;
&#xD;
             -  Intervention group (SIMPLe 2.0 + TAU): The experimental group will use the&#xD;
                application SIMPLe 2.0 and simultaneously will receive their usual treatment which&#xD;
                includes pharmacological and psychological interventions. A smart-phone device with&#xD;
                the SIMPLe 2.0 application pre-installed, will be given to the participants for&#xD;
                free during the study with the mandatory condition that it has to be their main&#xD;
                mobile-phone during the next 3 months. In the case the patient accept to&#xD;
                participate but don´t want to switch from their current smart-phone, they will be&#xD;
                offered the possibility to download the SIMPLe 2.0 application from the App Store&#xD;
                and a username and password will be given to use it. The patient will be asked by&#xD;
                customizable automatic reminder notifications to answer daily and weekly&#xD;
                questionnaires based on DSM-5 (Diagnostic and Statistical Manual of Mental&#xD;
                Disorders, 5th edition) criteria for a manic, hypomanic or depressive episode.&#xD;
                Additionally, the signs will be automatically recorded based on the smart-phone&#xD;
                usage measured by the smart-phone screen on time, texts messages sent, telephone&#xD;
                calls made and social networking apps activity, in addition to the physical&#xD;
                activity monitored by the built-in actimeter. At the same time, they will receive&#xD;
                through the application daily psychoeducative customized messages based on the data&#xD;
                recollected by the application. Relapse risk will be fixed by means of a logarithm&#xD;
                including both subjective and objective data. If the logarithm points at a moderate&#xD;
                or high risk, the clinical team will be immediately contacted and the patient will&#xD;
                be offered to call emergency services for assistance.&#xD;
&#xD;
             -  Treatment as usual group (TAU): The treatment as usual (TAU) only group will be&#xD;
                followed-up with their usual treatment including pharmacological and psychological&#xD;
                interventions.&#xD;
&#xD;
      An initial evaluation in both groups will be carried out recollecting sociodemographic data&#xD;
      and using standardized clinical as well as functional assessments which will be administered&#xD;
      again in three follow-up evaluations, at three, six and twelve months. The assessments will&#xD;
      include present manic symptoms using the Young Mania Rating Scale (YMRS), depressive symptoms&#xD;
      using the Hamilton depression Rating Scale (HDRS), functional impairment using the&#xD;
      Functioning assessment short test (FAST), biological rhythms using the biological rhythms&#xD;
      interview of assessment in neuropsychiatry (BRIAN), quality of life measured by World Health&#xD;
      Organization quality of life assessment (WHOQOL-BREF) and treatment adherence using the&#xD;
      Medication Adherence Rating Scale (MARS). During the follow-up the number of relapses,&#xD;
      inpatient admissions, outpatient consultations, emergency rooms consultations and suicide&#xD;
      attempts will be registered. All participants in both groups must read and agree with the&#xD;
      terms and sign an informed consent prior to their inclusion in the study. Psychiatrists and&#xD;
      psychologists conducting the evaluations will be blinded to which participant belongs to each&#xD;
      group.&#xD;
&#xD;
      The main outcome to evaluate between both groups during this period will be number of&#xD;
      relapses (Manic, Hypomanic or Depressive Episodes) during the 6-month treatment phase.&#xD;
      Secondary outcomes will include the number of relapses during 6-month post-intervention&#xD;
      follow-up (Manic, hypomanic and depressive episodes according to DSM-5 criteria). In addition&#xD;
      differences in biological rhythms (BRIAN), differences in manic symptoms using the Young&#xD;
      Mania Rating Scale (YMRS) and depressive symptoms using the Hamilton depression Rating Scale&#xD;
      (HDRS) during the 6-month treatment phase and 6-month post-intervention follow-up.&#xD;
      Additionally the quality of life (WHOQOL-BREF), functional Impairment (FAST) and treatment&#xD;
      adherence (Medication Adherence Rating Scale (MARS)) will be assessed each follow-up&#xD;
      assessment. Other outcomes include differences in healthcare resource consumption measured in&#xD;
      number and duration of hospitalizations, outpatient and emergency room consultations related&#xD;
      to their psychiatric disorder and pharmacological treatment changes (doses and agents&#xD;
      prescribed) over the 12 month follow-up.&#xD;
&#xD;
      In the case of positive results, the tested app will allow a user-friendly, non-costly and&#xD;
      efficacious way to monitor and train stable bipolar patients avoiding recurrences, as an&#xD;
      add-on to usual pharmacological care. The implementation of this technology will also improve&#xD;
      associated healthcare costs.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Suspended</overall_status>
  <why_stopped>
    Logistical problems.&#xD;
  </why_stopped>
  <start_date>October 2014</start_date>
  <completion_date type="Anticipated">November 2020</completion_date>
  <primary_completion_date type="Anticipated">March 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of relapses during intervention</measure>
    <time_frame>During the entire 6 months study period</time_frame>
    <description>Number of relapses during intervention (manic, hypomanic and depressive episodes according to DSM-5 criteria).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Biological rhythms</measure>
    <time_frame>During the entire 6 months study period of the clinical trial and during 6-month post-intervention follow-up</time_frame>
    <description>Difference in biological rhythms using the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) during the entire 6 months study period of the clinical trial and during 6-month post-intervention follow-up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Relapses during 6-month post-intervention</measure>
    <time_frame>6-months post-intervention</time_frame>
    <description>Number of Relapses during 6-month post-intervention follow-up (Manic, hypomanic and depressive episodes according to DSM-5 criteria).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Manic and depressive symptoms</measure>
    <time_frame>During the entire 6 months study period</time_frame>
    <description>Difference in manic symptoms using the Young Mania Rating Scale (YMRS), depressive symptoms using the Hamilton depression Rating Scale (HDRS) during the entire 6 months study period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life</measure>
    <time_frame>During the entire 6 months study period of the clinical trial and during 6-month post-intervention follow-up</time_frame>
    <description>Difference in quality of life measured by World Health Organization quality of life assessment (WHOQOL-BREF) during the entire 6 months study period of the clinical trial and during 6-month post-intervention follow-up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment adherence</measure>
    <time_frame>During the entire 6 months study period of the clinical trial and during 6-month post-intervention follow-up</time_frame>
    <description>Difference in treatment adherence using the Medication Adherence Rating Scale (MARS) during the entire 6 months study period of the clinical trial and during 6-month post-intervention follow-up.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional impairment</measure>
    <time_frame>During the entire 6 months study period of the clinical trial and during 6-month post-intervention follow-up.</time_frame>
    <description>Difference in functional impairment using the Functioning Assessment Short Test (FAST) during the entire 6 months study period of the clinical trial and during 6-month post-intervention follow-up.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">148</enrollment>
  <condition>Bipolar Disorder</condition>
  <arm_group>
    <arm_group_label>SIMPLe 2.0 plus Treatment as Usual (TAU)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Psychoeducative and self-monitoring smart-phone application plus treatment as usual which includes pharmacological and psychological treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment as usual (TAU)</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Treatment as usual which includes pharmacological and psychological treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>SIMPLE 2.0</intervention_name>
    <description>SIMPLE 2.0 psychoeducative and self-monitoring smart-phone application plus treatment as usual.</description>
    <arm_group_label>SIMPLe 2.0 plus Treatment as Usual (TAU)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with the current diagnosis of Bipolar disorder type I or type II according to&#xD;
             current DSM-5 criteria and confirmed with a semi structured interview (SCID).&#xD;
&#xD;
          -  Hamilton Depression Scale score under or equal to 8 during the last month.&#xD;
&#xD;
          -  Young Mania Rating Scale score under or equal to 6 during the last month.&#xD;
&#xD;
          -  No history of relapses during the last 3 previous months but at least 1 relapse during&#xD;
             the last year.&#xD;
&#xD;
          -  Availability of a telephone account with an unlimited data plan during the 12&#xD;
             following months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Lack of skills to use the offered smart-phone or unwillingness to learn them.&#xD;
&#xD;
          -  FAST score above or equal to 20.&#xD;
&#xD;
          -  Past or current participation in psychoeducation groups.&#xD;
&#xD;
          -  Obsessive-compulsive disorder according to DSM-5 criteria.&#xD;
&#xD;
          -  Concomitant severe medical condition.&#xD;
&#xD;
          -  Pregnancy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Francesc Colom, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Institut Hospital del Mar d'Investigacions Mèdiques (IMIM)</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Eduard Vieta, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Hospital Clínic of Barcelona</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Instituto Hospital del Mar de Investigaciones Médicas</name>
      <address>
        <city>Barcelona</city>
        <state>Catalonia</state>
        <zip>08003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>October 3, 2014</study_first_submitted>
  <study_first_submitted_qc>October 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 7, 2014</study_first_posted>
  <last_update_submitted>December 1, 2018</last_update_submitted>
  <last_update_submitted_qc>December 1, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 4, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital Clinic of Barcelona</investigator_affiliation>
    <investigator_full_name>Diego Hidalgo-Mazzei</investigator_full_name>
    <investigator_title>Diego Hidalgo-Mazzei, M.D.</investigator_title>
  </responsible_party>
  <keyword>Bipolar disorder</keyword>
  <keyword>Psychoeducation</keyword>
  <keyword>Smart-phone monitoring</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bipolar Disorder</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/NCT02258711
org study id: HCPPFR02062014
nct id: NCT02258711
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
Bipolar disorder is a frequent condition in the general population with a high
      morbimortality, which consists in dysfunctional temporal fluctuations between different mood
      phases ranging from depression to manic episodes with frequent subsyndromal symptoms between
      them. Usually during these phases, the subjects have a lack of insight about the diagnosis
      and symptoms. Besides the pharmacological treatment, additional psychological interventions
      have shown to improve the long-term outcome of the disorder, yet taking into account the
      limited resources currently available, its general implementation is still difficult and
      costly. Among these interventions, group psychoeducational programs have proved to be
      cost-effective in helping patients recognize early signs and symptoms in order to prevent
      full blown episodes which very usually are associated with a high morbidity and hospital
      admissions.

      On the other hand, numerous projects have tested the potential benefits of new technologies
      such internet in the treatment of bipolar and psychotic disorders patients using either
      online signs and symptoms monitoring or web-based psychoeducational programs, yet to the
      investigators knowledge, none of them have integrated both approaches in one single
      intervention.

      The hypothesis that, combining both interventions (signs and symptoms monitoring along with
      psychoeducational contents) in a single smart-phone application will prove to be at least
      equal or superior in terms of efficacy comparing to the standard treatment, seems promising,
      given the fact that both approaches have independently demonstrated their efficacy in the
      same population. This could extend the range of the patients in whom this kind of additional
      interventions could be implemented; preventing relapses, suicide attempts, consultations and
      hospitalizations at a much lower cost.
The main aim of this study is to develop and clinically validate a smart-phone application to
      monitor symptoms and signs in stable bipolar patients, offering also customized embedded
      psycho-education contents and empower the self-management of their disorder to avoid relapses
      and hospitalizations. Secondary objectives will be to explore other clinical benefits among
      the smart-phone application users such as biological rhythms, manic/hypomanic and depressive
      symptoms, quality of life, suicide attempts, pharmacological treatment changes as well as
      healthcare resource consumption (outpatient and emergency room consultations) in order to
      evaluate its cost-efficiency compared to current standard interventions.

      The study will include stable bipolar patients (YMRS ≤ 8, HDRS ≤ 6 for at least one month
      prior to study entry) who have experienced at least one hypomanic, manic or depressive
      relapse during the 12 months prior to study entry. This will be carried out in three
      different but complementary phases in order to fully include patients and therapist's
      preferences. Along the process, confidential information and data handling will be tested to
      ensure privacy and confidentiality are warranted. In this regard, an anonymized user name and
      password will be given to the patients who will never have to reveal their real identity to
      access the application during the study.

        -  First phase: During the first three months a feasibility study will be conducted
           evaluating the use, reliability and satisfaction monitoring symptoms (subjective
           information) using a smart-phone with the SIMPLe 1.0 application installed. The
           intervention will be consecutively offered to 30 stable adults (>18 years) fulfilling
           inclusion criteria. The patient will have to read and agree with the terms and sign an
           informed consent in order to participate. Sociodemographic data and standardized
           clinical as well as functional assessments will be administered at baseline, at the
           first, second and third month of the study. The assessments will include present manic
           symptoms using the Young Mania Rating Scale (YMRS), depressive symptoms using the
           Hamilton depression Rating Scale (HDRS), biological rhythms using the biological rhythms
           interview of assessment in neuropsychiatry (BRIAN), quality of life measured by World
           Health Organization quality of life assessment (WHOQOL-BREF) and treatment adherence
           using the Medication Adherence Rating Scale (MARS). A smart-phone device with the SIMPLe
           1.0 application pre-installed, will be given to the participants for free during the
           study with the mandatory condition that it has to be their main mobile-phone during the
           next 3 months. In the case the patient accepts to participate but doesn´t want to switch
           from his/her current smart-phone, he/she will be offered the possibility to download the
           SIMPLe 1.0 application from the App Store and a username and password will be given to
           use it. The SIMPLe 1.0 application will ask the user by customizable automatic reminder
           notifications to answer daily and weekly questionnaires based on DSM-5 (Diagnostic and
           Statistical Manual of Mental Disorders, 5th edition) criteria for a manic, hypomanic,
           mixed or depressive episode. The use frequency will be measured by the daily and weekly
           questionnaires answered which will be registered online. At the same time they will
           receive through the application daily customized psychoeducative messages based on the
           information collected by the application. Feasibility and satisfaction will be assessed
           with the application usage log data and an electronic survey, while the app reliability
           to correctly asses the patients mood states will be analyzed comparing the clinical
           assessments and the information collected by the application.

        -  Second phase: Individual personal interviews with each SIMPLe 1.0 user will also collect
           qualitative information about the application and suggestions. Taking into consideration
           the information collected from participants in the first phase, the application will be
           adapted and improved with the addition of objective information (signs) monitoring
           modules using mobile usage parameters and the built-in sensors. Focus groups will be
           held with participants, psychiatrists and psychologists to better fit their needs and
           incorporate suggestions.

        -  Third phase: A randomized controlled trial taking into consideration a significance
           level of 0.05, power of 0.8 and a minimal detectable difference of 0.5 and an expected
           drop-out of 15%, will be carried out with two arms of 74 patients each, as follows:

             -  Intervention group (SIMPLe 2.0 + TAU): The experimental group will use the
                application SIMPLe 2.0 and simultaneously will receive their usual treatment which
                includes pharmacological and psychological interventions. A smart-phone device with
                the SIMPLe 2.0 application pre-installed, will be given to the participants for
                free during the study with the mandatory condition that it has to be their main
                mobile-phone during the next 3 months. In the case the patient accept to
                participate but don´t want to switch from their current smart-phone, they will be
                offered the possibility to download the SIMPLe 2.0 application from the App Store
                and a username and password will be given to use it. The patient will be asked by
                customizable automatic reminder notifications to answer daily and weekly
                questionnaires based on DSM-5 (Diagnostic and Statistical Manual of Mental
                Disorders, 5th edition) criteria for a manic, hypomanic or depressive episode.
                Additionally, the signs will be automatically recorded based on the smart-phone
                usage measured by the smart-phone screen on time, texts messages sent, telephone
                calls made and social networking apps activity, in addition to the physical
                activity monitored by the built-in actimeter. At the same time, they will receive
                through the application daily psychoeducative customized messages based on the data
                recollected by the application. Relapse risk will be fixed by means of a logarithm
                including both subjective and objective data. If the logarithm points at a moderate
                or high risk, the clinical team will be immediately contacted and the patient will
                be offered to call emergency services for assistance.

             -  Treatment as usual group (TAU): The treatment as usual (TAU) only group will be
                followed-up with their usual treatment including pharmacological and psychological
                interventions.

      An initial evaluation in both groups will be carried out recollecting sociodemographic data
      and using standardized clinical as well as functional assessments which will be administered
      again in three follow-up evaluations, at three, six and twelve months. The assessments will
      include present manic symptoms using the Young Mania Rating Scale (YMRS), depressive symptoms
      using the Hamilton depression Rating Scale (HDRS), functional impairment using the
      Functioning assessment short test (FAST), biological rhythms using the biological rhythms
      interview of assessment in neuropsychiatry (BRIAN), quality of life measured by World Health
      Organization quality of life assessment (WHOQOL-BREF) and treatment adherence using the
      Medication Adherence Rating Scale (MARS). During the follow-up the number of relapses,
      inpatient admissions, outpatient consultations, emergency rooms consultations and suicide
      attempts will be registered. All participants in both groups must read and agree with the
      terms and sign an informed consent prior to their inclusion in the study. Psychiatrists and
      psychologists conducting the evaluations will be blinded to which participant belongs to each
      group.

      The main outcome to evaluate between both groups during this period will be number of
      relapses (Manic, Hypomanic or Depressive Episodes) during the 6-month treatment phase.
      Secondary outcomes will include the number of relapses during 6-month post-intervention
      follow-up (Manic, hypomanic and depressive episodes according to DSM-5 criteria). In addition
      differences in biological rhythms (BRIAN), differences in manic symptoms using the Young
      Mania Rating Scale (YMRS) and depressive symptoms using the Hamilton depression Rating Scale
      (HDRS) during the 6-month treatment phase and 6-month post-intervention follow-up.
      Additionally the quality of life (WHOQOL-BREF), functional Impairment (FAST) and treatment
      adherence (Medication Adherence Rating Scale (MARS)) will be assessed each follow-up
      assessment. Other outcomes include differences in healthcare resource consumption measured in
      number and duration of hospitalizations, outpatient and emergency room consultations related
      to their psychiatric disorder and pharmacological treatment changes (doses and agents
      prescribed) over the 12 month follow-up.

      In the case of positive results, the tested app will allow a user-friendly, non-costly and
      efficacious way to monitor and train stable bipolar patients avoiding recurrences, as an
      add-on to usual pharmacological care. The implementation of this technology will also improve
      associated healthcare costs.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Care Provider)
measure: Number of relapses during intervention
time frame: During the entire 6 months study period
description: Number of relapses during intervention (manic, hypomanic and depressive episodes according to DSM-5 criteria).
measure: Biological rhythms
time frame: During the entire 6 months study period of the clinical trial and during 6-month post-intervention follow-up
description: Difference in biological rhythms using the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) during the entire 6 months study period of the clinical trial and during 6-month post-intervention follow-up.
measure: Number of Relapses during 6-month post-intervention
time frame: 6-months post-intervention
description: Number of Relapses during 6-month post-intervention follow-up (Manic, hypomanic and depressive episodes according to DSM-5 criteria).
measure: Number of Manic and depressive symptoms
time frame: During the entire 6 months study period
description: Difference in manic symptoms using the Young Mania Rating Scale (YMRS), depressive symptoms using the Hamilton depression Rating Scale (HDRS) during the entire 6 months study period.
measure: Quality of life
time frame: During the entire 6 months study period of the clinical trial and during 6-month post-intervention follow-up
description: Difference in quality of life measured by World Health Organization quality of life assessment (WHOQOL-BREF) during the entire 6 months study period of the clinical trial and during 6-month post-intervention follow-up.
measure: Treatment adherence
time frame: During the entire 6 months study period of the clinical trial and during 6-month post-intervention follow-up
description: Difference in treatment adherence using the Medication Adherence Rating Scale (MARS) during the entire 6 months study period of the clinical trial and during 6-month post-intervention follow-up.
measure: Functional impairment
time frame: During the entire 6 months study period of the clinical trial and during 6-month post-intervention follow-up.
description: Difference in functional impairment using the Functioning Assessment Short Test (FAST) during the entire 6 months study period of the clinical trial and during 6-month post-intervention follow-up.
arm group label: SIMPLe 2.0 plus Treatment as Usual (TAU)
arm group type: Experimental
description: Psychoeducative and self-monitoring smart-phone application plus treatment as usual which includes pharmacological and psychological treatment.
arm group label: Treatment as usual (TAU)
arm group type: No Intervention
description: Treatment as usual which includes pharmacological and psychological treatment.
intervention type: Device
intervention name: SIMPLE 2.0
description: SIMPLE 2.0 psychoeducative and self-monitoring smart-phone application plus treatment as usual.
arm group label: SIMPLe 2.0 plus Treatment as Usual (TAU)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Francesc Colom, PhD
role: Study Director
affiliation: Institut Hospital del Mar d'Investigacions Mèdiques (IMIM)
last name: Eduard Vieta, MD, PhD
role: Study Chair
affiliation: Hospital Clínic of Barcelona
facility: 
country: Spain
responsible party type: Principal Investigator
investigator affiliation: Hospital Clinic of Barcelona
investigator full name: Diego Hidalgo-Mazzei
investigator title: Diego Hidalgo-Mazzei, M.D.
mesh term: Bipolar Disorder