<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/NCT04454073</url>
  </required_header>
  <id_info>
    <org_study_id>67144</org_study_id>
    <nct_id>NCT04454073</nct_id>
  </id_info>
  <brief_title>Investigation of Factors Associated With Preserved Cognitive Function in Bipolar Disorder</brief_title>
  <official_title>Investigation of Factors Associated With Preserved Cognitive Function in Bipolar Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St. Olavs Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>St. Olavs Hospital</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>
      Bipolar disorder (BD) ïs the fourth leading cause of disability worldwide among young people.&#xD;
      Differences in demographic and clinical characteristics between patients do not influence&#xD;
      educational achievement and receipt of disability pension, indicating that there are other&#xD;
      factors such as neurocognitive function that are of importance for maintaining occupational&#xD;
      and social function. Research has shown that at the group level, cognitive deficits are&#xD;
      present in euthymic BD patients, while approximately 30%-50% of BD patients is not different&#xD;
      from healthy controls when it comes to cognitive function. There is however little knowledge&#xD;
      of risk and resilience factors for cognitive impairment in BD. Factors likely to contribute&#xD;
      to cognitive and functional outcomes in BD, such as sleep, obesity, biological rhythms,&#xD;
      comorbid medical and psychiatric conditions are also understudied. While it has been&#xD;
      customary to focus research on factors related to the negative illness trajectories, the&#xD;
      overarching aim of the current project is to explore factors associated with favourable&#xD;
      outcomes. This shift in research focus is essential to elucidate factors related to more&#xD;
      preserved function since this represents a clear gap in knowledge today.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an observational and prospective study aimed at identifying risk and resilience&#xD;
      factors for cognitive impairment in BD. The investigators will enrol 85 participants with&#xD;
      bipolar disorder. The assessment period is from one up to two weeks. At inclusion, the&#xD;
      investigators will examine other psychiatric conditions, known somatic diseases and symptom&#xD;
      levels of depression and hypo-/mania. Insomnia severity and risk factors for metabolic&#xD;
      syndrome will also be assessed. Secondly, the investigators will examine sleep and Activity&#xD;
      extensively with both subjective and objective measures for one to two weeks. Third, a newly&#xD;
      developed web-based neuropsychological test protocol will be used shortly after assessment of&#xD;
      sleep and activity to test cognitive function. Fourth, alcohol use, substance use and&#xD;
      biological rhythms will be assessed. Lastly, the investigators will retest cognitive function&#xD;
      and symptom levels up to five years after enrolment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 29, 2021</start_date>
  <completion_date type="Anticipated">May 2025</completion_date>
  <primary_completion_date type="Anticipated">May 2025</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Assessment of cognitive function in bipolar patients</measure>
    <time_frame>On day 7 after inclusion</time_frame>
    <description>Memoro is a self-administered web-based neuropsychological test platform. All tests include both written and auditory instructions. The Memoro will be used to assess objective cognitive function. It contains measures of learning, storing, recalling and recognizing visual and verbal information, pattern separation, and verbal memory span, verbal working memory, processing speed, reaction time and cognitive control. Time frame: After examination of sleep and activity for a period of up to two weeks. Results from the test will be converted to z-scores.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessing change of cognitive function in bipolar patients</measure>
    <time_frame>Up to 5 years after inclusion</time_frame>
    <description>Memoro is a self-administered web-based neuropsychological test platform. All tests include both written and auditory instructions. It contains measures of learning, storing, recalling and recognizing visual and verbal information, pattern separation, and verbal memory span, verbal working memory, processing speed, reaction time and cognitive control. The Memoro will be used to assess stability or change in objective cognitive function.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Diagnostic evaluation With Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I)</measure>
    <time_frame>Day 1</time_frame>
    <description>This measure will be used to determine if participants meet the diagnostic criteria for Bipolar Disorder. This is a yes/no diagnostic tool and our data indicate percentage who meet criteria for bipolar type I or type II.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants With comorbid psychiatric disorders.</measure>
    <time_frame>Day 1</time_frame>
    <description>Mini International Neuropsychiatric Interview (MINI) is a short diagnostic structured interview developed to explore 16 disorders including suicidality according to Diagnostic and Statistical Manual diagnostic criteria (DSM). The data will be used to assess the presence of other psychiatric conditions than bipolar disorder (yes/no).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Montgomery Åsberg Depression Rating Scale (MADRS)</measure>
    <time_frame>Day 1</time_frame>
    <description>MADRS will be used to assess depressive symptoms. Range is 0-60. Higher score indicate more severe depressive symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Young Mania Rating Scale (YMRS)</measure>
    <time_frame>Day 1</time_frame>
    <description>YMRS will be used to assess hypo-/manic symptoms. Range is 0 to 60. Higher score indicate more severe manic symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insomnia Severity Index (ISI)</measure>
    <time_frame>Day 1</time_frame>
    <description>A self-reported questionnaire of insomnia severity. Range is 08-28. Higher values represent higher levels of insomnia symptom severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Medication use</measure>
    <time_frame>Day 1</time_frame>
    <description>Daily doses and classes of medications (e.g. antipsychotics, mood stabilizers, benzodiazepines, etc.) prescribed per individual by the time of inclusion will be recorded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Actigraph</measure>
    <time_frame>1 week</time_frame>
    <description>Actigraph is a small device usually worn on the wrist that records the activity level of the body by sensing physical movement. The actigraph will be used to objectively assess sleep variables and daytime activity parameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sleep diary</measure>
    <time_frame>1 week</time_frame>
    <description>A self-reported record of the participants' sleeping and waking times.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Xethru sleep radar</measure>
    <time_frame>1 week</time_frame>
    <description>Xethru sleep radar is a low-powered ultra-wideband sensor that allows contact-free assessment of sleep patterns and wakefulness with high accuracy compared to polysomnographic (PSG) recordings. The radar will stand on the participants' bedside tables</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oximetry</measure>
    <time_frame>1 day (1 night during period of sleep assessment)</time_frame>
    <description>Oximetry is a measurement of the blood's oxygen saturation. It will be used to assess any indication of sleep apnea for one night during the period of sleep assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Functioning Assessment Short Test (FAST)</measure>
    <time_frame>7 days after inclusion</time_frame>
    <description>FAST will be used to assess functional outcomes. Range is 0-72. Higher values indicate greater disability</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive complaints in Bipolar disorder Rating Assessment (COBRA)</measure>
    <time_frame>7 days after inclusion</time_frame>
    <description>COBRA is an assessment of subjective cognitive dysfunction. Range is 0-48 and higher scores indicate more cognitive complaints.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN)</measure>
    <time_frame>7 days after inclusion</time_frame>
    <description>BRIAN is an assessment of circadian rhythms disturbance. Range is 1 to 72 and higher score indicate more severe disturbance of circadian rhythms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alcohol use disorders identification test (AUDIT)</measure>
    <time_frame>7 days after inclusion</time_frame>
    <description>AUDIT is an assessment of the frequency and quantity of alcohol consumption where higher scores indicate higher levels of use.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Drug use disorders identification test (DUDIT)</measure>
    <time_frame>7 days after inclusion</time_frame>
    <description>DUDIT is an assessment of the frequency and quantity of drug consumption where higher scores indicate higher levels of use.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants With Metabolic syndrome</measure>
    <time_frame>7 days after inclusion</time_frame>
    <description>The World Health Organisation criteria for the metabolic syndrome will be used in the dichotomisation of the metabolic factors: Systolic blood pressure will be dichotomised as ≤ 140 mmHg or &gt;140 mmHg and diastolic blood pressure as ≤ 90 mmHg or &gt; 90 mmHg. Triglycerides will be classified as &lt; 1.7 mmol/l or ≥ 1.7mmol/l. HDL cholesterol will be categorised as ≥ 1 mmol/l or &lt;1 mmol/l for women and ≥ 0.90 mmol/l or &lt;0.90 mmol/l for men. Fasting glucose will be defined as elevated when the plasma glucose levels is ≥7.0 mmol/l and two dichotomous groups will be created; &lt; 7.0 mmol/l or ≥ 7.0 mmol/l. Waist circumference will be measured at the level of the umbilicus, and the hip girth will be measured at the level of maximal protrusion of the gluteal muscles. Waist-to-hip ratio will be dichotomised as ≤ 0.85 or &gt; 0.85 for women and ≤ 0.90 or &gt; 0.90 for men. The waist circumference will be categorised as ≤ 88 cm or &gt; 0.88 for women and ≤ 102 cm or &gt;102 cm for men.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Numbers of participants With disturbances of Thyroid function</measure>
    <time_frame>7 days after inclusion</time_frame>
    <description>Normal thyroid function is considered thyroid stimulating hormone (TSH) levels in the range from 0.24 to 3.78 mIU/l and T4 levels in the range of 13.5 to 21.2 pmol/l.&#xD;
Latent and subclinical biochemical hypothyroidism; with an elevation of TSH with T4 in the normal range.&#xD;
Overt biochemical hypothyroidism: elevated TSH and a decrease of T4 levels. Biochemical hyperthyroidism and latent biochemical hyperthyroidism: TSH levels below the normal range with and without elevated T4.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">85</enrollment>
  <condition>Bipolar Disorder</condition>
  <arm_group>
    <arm_group_label>Bipolar patients</arm_group_label>
    <description>In euthymic state or with mild to moderate symptoms</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Bipolar patients diagnosed with Bipolar disorder I or II, in euthymic state or with mild to&#xD;
        moderate symptoms at time of assessment.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Individuals aged &gt;=18 years who score &lt;= 16 on the MADRS or &lt;= 8 on the YMRS.&#xD;
&#xD;
          -  Willing and able to give online informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Symptom level above inclusion criteria will be put on a waiting list, and if informed&#xD;
             consent is given, will be included when symptom level is reduced.&#xD;
&#xD;
          -  No Norwegian fluency.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Randolf Vaagen</last_name>
    <role>Study Director</role>
    <affiliation>St Olavs Hospital, Division of Mental Health Care</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Anne Engum, phd</last_name>
    <role>Principal Investigator</role>
    <affiliation>St Olavs Hospital, Division of Mental Health Care</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Knut Langsrud</last_name>
    <role>Study Director</role>
    <affiliation>St Olavs Hospital, Division of Mental Health Care</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kristin Svee</last_name>
    <phone>+4795418907</phone>
    <email>kristin.svee@stolav.no</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Anne Engum, phd</last_name>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Bipolar and sleep outpatient clinic, Department of Østmarka, Division of Mental Health Care</name>
      <address>
        <city>Trondheim</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kristin Svee</last_name>
      <email>kristin.svee@stolav.no</email>
    </contact>
  </location>
  <location_countries>
    <country>Norway</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>June 8, 2020</study_first_submitted>
  <study_first_submitted_qc>June 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 1, 2020</study_first_posted>
  <last_update_submitted>November 2, 2022</last_update_submitted>
  <last_update_submitted_qc>November 2, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 3, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cognition</keyword>
  <keyword>Cross-sectional Studies</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/NCT04454073
org study id: 67144
nct id: NCT04454073
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Bipolar disorder (BD) ïs the fourth leading cause of disability worldwide among young people.
      Differences in demographic and clinical characteristics between patients do not influence
      educational achievement and receipt of disability pension, indicating that there are other
      factors such as neurocognitive function that are of importance for maintaining occupational
      and social function. Research has shown that at the group level, cognitive deficits are
      present in euthymic BD patients, while approximately 30%-50% of BD patients is not different
      from healthy controls when it comes to cognitive function. There is however little knowledge
      of risk and resilience factors for cognitive impairment in BD. Factors likely to contribute
      to cognitive and functional outcomes in BD, such as sleep, obesity, biological rhythms,
      comorbid medical and psychiatric conditions are also understudied. While it has been
      customary to focus research on factors related to the negative illness trajectories, the
      overarching aim of the current project is to explore factors associated with favourable
      outcomes. This shift in research focus is essential to elucidate factors related to more
      preserved function since this represents a clear gap in knowledge today.
This is an observational and prospective study aimed at identifying risk and resilience
      factors for cognitive impairment in BD. The investigators will enrol 85 participants with
      bipolar disorder. The assessment period is from one up to two weeks. At inclusion, the
      investigators will examine other psychiatric conditions, known somatic diseases and symptom
      levels of depression and hypo-/mania. Insomnia severity and risk factors for metabolic
      syndrome will also be assessed. Secondly, the investigators will examine sleep and Activity
      extensively with both subjective and objective measures for one to two weeks. Third, a newly
      developed web-based neuropsychological test protocol will be used shortly after assessment of
      sleep and activity to test cognitive function. Fourth, alcohol use, substance use and
      biological rhythms will be assessed. Lastly, the investigators will retest cognitive function
      and symptom levels up to five years after enrolment.
observational model: Case-Only
time perspective: Cross-Sectional
measure: Assessment of cognitive function in bipolar patients
time frame: On day 7 after inclusion
description: Memoro is a self-administered web-based neuropsychological test platform. All tests include both written and auditory instructions. The Memoro will be used to assess objective cognitive function. It contains measures of learning, storing, recalling and recognizing visual and verbal information, pattern separation, and verbal memory span, verbal working memory, processing speed, reaction time and cognitive control. Time frame: After examination of sleep and activity for a period of up to two weeks. Results from the test will be converted to z-scores.
measure: Assessing change of cognitive function in bipolar patients
time frame: Up to 5 years after inclusion
description: Memoro is a self-administered web-based neuropsychological test platform. All tests include both written and auditory instructions. It contains measures of learning, storing, recalling and recognizing visual and verbal information, pattern separation, and verbal memory span, verbal working memory, processing speed, reaction time and cognitive control. The Memoro will be used to assess stability or change in objective cognitive function.
measure: Diagnostic evaluation With Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I)
time frame: Day 1
description: This measure will be used to determine if participants meet the diagnostic criteria for Bipolar Disorder. This is a yes/no diagnostic tool and our data indicate percentage who meet criteria for bipolar type I or type II.
measure: Number of participants With comorbid psychiatric disorders.
time frame: Day 1
description: Mini International Neuropsychiatric Interview (MINI) is a short diagnostic structured interview developed to explore 16 disorders including suicidality according to Diagnostic and Statistical Manual diagnostic criteria (DSM). The data will be used to assess the presence of other psychiatric conditions than bipolar disorder (yes/no).
measure: Montgomery Åsberg Depression Rating Scale (MADRS)
time frame: Day 1
description: MADRS will be used to assess depressive symptoms. Range is 0-60. Higher score indicate more severe depressive symptoms.
measure: Young Mania Rating Scale (YMRS)
time frame: Day 1
description: YMRS will be used to assess hypo-/manic symptoms. Range is 0 to 60. Higher score indicate more severe manic symptoms.
measure: Insomnia Severity Index (ISI)
time frame: Day 1
description: A self-reported questionnaire of insomnia severity. Range is 08-28. Higher values represent higher levels of insomnia symptom severity.
measure: Medication use
time frame: Day 1
description: Daily doses and classes of medications (e.g. antipsychotics, mood stabilizers, benzodiazepines, etc.) prescribed per individual by the time of inclusion will be recorded.
measure: Actigraph
time frame: 1 week
description: Actigraph is a small device usually worn on the wrist that records the activity level of the body by sensing physical movement. The actigraph will be used to objectively assess sleep variables and daytime activity parameters.
measure: Sleep diary
time frame: 1 week
description: A self-reported record of the participants' sleeping and waking times.
measure: Xethru sleep radar
time frame: 1 week
description: Xethru sleep radar is a low-powered ultra-wideband sensor that allows contact-free assessment of sleep patterns and wakefulness with high accuracy compared to polysomnographic (PSG) recordings. The radar will stand on the participants' bedside tables
measure: Oximetry
time frame: 1 day (1 night during period of sleep assessment)
description: Oximetry is a measurement of the blood's oxygen saturation. It will be used to assess any indication of sleep apnea for one night during the period of sleep assessment
measure: The Functioning Assessment Short Test (FAST)
time frame: 7 days after inclusion
description: FAST will be used to assess functional outcomes. Range is 0-72. Higher values indicate greater disability
measure: Cognitive complaints in Bipolar disorder Rating Assessment (COBRA)
time frame: 7 days after inclusion
description: COBRA is an assessment of subjective cognitive dysfunction. Range is 0-48 and higher scores indicate more cognitive complaints.
measure: The Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN)
time frame: 7 days after inclusion
description: BRIAN is an assessment of circadian rhythms disturbance. Range is 1 to 72 and higher score indicate more severe disturbance of circadian rhythms.
measure: Alcohol use disorders identification test (AUDIT)
time frame: 7 days after inclusion
description: AUDIT is an assessment of the frequency and quantity of alcohol consumption where higher scores indicate higher levels of use.
measure: Drug use disorders identification test (DUDIT)
time frame: 7 days after inclusion
description: DUDIT is an assessment of the frequency and quantity of drug consumption where higher scores indicate higher levels of use.
measure: Number of participants With Metabolic syndrome
time frame: 7 days after inclusion
description: The World Health Organisation criteria for the metabolic syndrome will be used in the dichotomisation of the metabolic factors: Systolic blood pressure will be dichotomised as ≤ 140 mmHg or >140 mmHg and diastolic blood pressure as ≤ 90 mmHg or > 90 mmHg. Triglycerides will be classified as < 1.7 mmol/l or ≥ 1.7mmol/l. HDL cholesterol will be categorised as ≥ 1 mmol/l or <1 mmol/l for women and ≥ 0.90 mmol/l or <0.90 mmol/l for men. Fasting glucose will be defined as elevated when the plasma glucose levels is ≥7.0 mmol/l and two dichotomous groups will be created; < 7.0 mmol/l or ≥ 7.0 mmol/l. Waist circumference will be measured at the level of the umbilicus, and the hip girth will be measured at the level of maximal protrusion of the gluteal muscles. Waist-to-hip ratio will be dichotomised as ≤ 0.85 or > 0.85 for women and ≤ 0.90 or > 0.90 for men. The waist circumference will be categorised as ≤ 88 cm or > 0.88 for women and ≤ 102 cm or >102 cm for men.
measure: Numbers of participants With disturbances of Thyroid function
time frame: 7 days after inclusion
description: Normal thyroid function is considered thyroid stimulating hormone (TSH) levels in the range from 0.24 to 3.78 mIU/l and T4 levels in the range of 13.5 to 21.2 pmol/l.
Latent and subclinical biochemical hypothyroidism; with an elevation of TSH with T4 in the normal range.
Overt biochemical hypothyroidism: elevated TSH and a decrease of T4 levels. Biochemical hyperthyroidism and latent biochemical hyperthyroidism: TSH levels below the normal range with and without elevated T4.
arm group label: Bipolar patients
description: In euthymic state or with mild to moderate symptoms
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Randolf Vaagen
role: Study Director
affiliation: St Olavs Hospital, Division of Mental Health Care
last name: Anne Engum, phd
role: Principal Investigator
affiliation: St Olavs Hospital, Division of Mental Health Care
last name: Knut Langsrud
role: Study Director
affiliation: St Olavs Hospital, Division of Mental Health Care
last name: Kristin Svee
phone: +4795418907
email: kristin.svee@stolav.no
last name: Anne Engum, phd
facility: 
status: Recruiting
contact: 
country: Norway
responsible party type: Sponsor
mesh term: Bipolar Disorder