<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/NCT03811860</url>
  </required_header>
  <id_info>
    <org_study_id>18-0289-A</org_study_id>
    <nct_id>NCT03811860</nct_id>
  </id_info>
  <brief_title>Lithium Therapeutic Drug Monitoring; Once Daily Vs Twice Daily Dosing and the Impact of Kidney Function</brief_title>
  <official_title>Lithium Therapeutic Drug Monitoring; Once Daily Vs Twice Daily Dosing and the Impact of Kidney Function</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mount Sinai Hospital, Canada</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mount Sinai Hospital, Canada</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Lithium is a mainstay in the treatment of bipolar disorder, and a frequently used adjunctive&#xD;
      therapy for major depressive disorder. It is accepted practice to monitor lithium serum&#xD;
      levels to monitor for efficacy and toxicity. However, studies on the difference in lithium&#xD;
      levels between once and twice daily dosing, which also assess the impact of kidney function&#xD;
      are scarce. The aim of this study is to quantify this pharmacokinetic difference, identify&#xD;
      the impact of kidney function, in the context of estimating effects to inform feasibility and&#xD;
      sample size needed for a larger well-powered study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Bipolar disorder is a chronic and recurring condition which causes functional impairment and&#xD;
      increases lifetime suicide risk. Major depressive disorder likewise confers a high burden of&#xD;
      illness on the affected population, and treatment is complicated by the fact 50-70% of&#xD;
      patients treated with an initial agent do not achieve full remission of symptoms. There are&#xD;
      numerous clinical practice guidelines which support the use of lithium as a first-line agent&#xD;
      for bipolar disorder, and as an adjunctive therapy for major depressive disorder. Therapeutic&#xD;
      ranges for lithium were established in the 1970s using multiple daily dose regimens, and&#xD;
      therefore should not be directly applied to patients taking lithium once daily. The current&#xD;
      standard of practice is to measure levels 12 hours post dose irrespective of once or twice&#xD;
      daily administration. There is some evidence that lithium levels drawn 12 hours post dose are&#xD;
      10 - 26% higher when dosing lithium once daily compared to twice daily, however, the impact&#xD;
      of kidney function on this difference has not been studied, and this difference in 12h post&#xD;
      levels has not been confirmed via prospective data. Guidance on therapeutic drug monitoring&#xD;
      (TDM) is vague with respect to interpretation of specific lithium blood levels for once daily&#xD;
      dosing. Physicians may reduce a patient's dose based on a lithium level that is seemingly&#xD;
      higher that target, even if the patient is clinically stable, putting the patient at risk for&#xD;
      re-emergence of symptoms. Though it is known that lithium is excreted by the kidney, the&#xD;
      impact of kidney function on the difference in lithium levels when dosed once daily compared&#xD;
      to twice daily is not well understood. The results of this pilot study will help identify the&#xD;
      impact of kidney function on lithium therapeutic drug monitoring in current practice, and&#xD;
      potentially lead to a larger multi-center study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">February 6, 2019</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">September 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Difference in lithium levels between once and twice daily dosing</measure>
    <time_frame>once 2 steady state levels have been taken (4-12 days of intervention)</time_frame>
    <description>The average of the difference in 12 hour post-dose serum level between the two dosing regimens (once daily and twice daily dosing)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Correlation between renal function and difference in lithium level</measure>
    <time_frame>once 2 steady state levels have been taken (4-12 days of intervention) and average creatinine clearance has been calculated</time_frame>
    <description>Calculated correlation coefficient (r) for renal function (as estimated by calculation of creatinine clearance via Cockroft Gault) and mean percent change in serum lithium concentration when transitioning between once and twice daily dosing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of selected concurrent medication use</measure>
    <time_frame>recorded upon enrollment, and every 4-6 days until study completion, up to 12 months</time_frame>
    <description>Frequency of thiazide diuretic, loop diuretic, NSAID, and ACE inhibitor/ARB use</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">15</enrollment>
  <condition>Bipolar Disorder</condition>
  <condition>Major Depressive Disorder</condition>
  <arm_group>
    <arm_group_label>Once Daily Dosing</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In this arm of the study, participants receive the prescribed dose of lithium once daily at bedtime. After 4-6 days, a steady state lithium serum level and serum creatinine are taken, and they crossover to the other arm (twice daily dosing, if they have not already done so). Frequency of selected medication use is noted.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Twice Daily Dosing</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In this arm of the study, participants receive the prescribed dose of lithium divided into two daily doses. After 4-6 days a steady state lithium serum level and serum creatinine are taken, and they crossover to the other arm (once daily dosing, if they have not already done so).Frequency of selected medication use is noted.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Lithium level</intervention_name>
    <description>The level of lithium in the serum</description>
    <arm_group_label>Once Daily Dosing</arm_group_label>
    <arm_group_label>Twice Daily Dosing</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Serum Creatinine</intervention_name>
    <description>The level of creatinine (as an indicator of kidney function, to approximate GFR) in the serum</description>
    <arm_group_label>Once Daily Dosing</arm_group_label>
    <arm_group_label>Twice Daily Dosing</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients admitted to the inpatient psychiatry unit at Mount Sinai Hospital&#xD;
             treated with lithium therapy (i.e. taking lithium before admission, or initiated on&#xD;
             lithium therapy during hospitalization)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  any patients who are currently pregnant&#xD;
&#xD;
          -  patients taking lithium three times daily&#xD;
&#xD;
          -  patients taking lithium with a specific dosing frequency for a documented clinical&#xD;
             reason.&#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_contact>
    <last_name>Virginia Fernandes, PharmD</last_name>
    <phone>416-586-4800</phone>
    <email>virginia.fernandes@sinaihealthsystem.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Dario A Moscoso, PharmD</last_name>
    <phone>416-586-4800</phone>
    <email>dario.moscoso@sinaihealthsystem.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Mount Sinai Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1X5</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Virginia Fernandes, PharmD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>January 10, 2019</study_first_submitted>
  <study_first_submitted_qc>January 18, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 22, 2019</study_first_posted>
  <last_update_submitted>March 6, 2019</last_update_submitted>
  <last_update_submitted_qc>March 6, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mount Sinai Hospital, Canada</investigator_affiliation>
    <investigator_full_name>Virginia Fernandes</investigator_full_name>
    <investigator_title>Clinical Practice Leader, Psychiatry</investigator_title>
  </responsible_party>
  <keyword>lithium</keyword>
  <keyword>pharmacokinetics</keyword>
  <keyword>renal</keyword>
  <keyword>kidney</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
    <mesh_term>Bipolar Disorder</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lithium Carbonate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>There is no such plan</ipd_description>
  </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/NCT03811860
org study id: 18-0289-A
nct id: NCT03811860
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Lithium is a mainstay in the treatment of bipolar disorder, and a frequently used adjunctive
      therapy for major depressive disorder. It is accepted practice to monitor lithium serum
      levels to monitor for efficacy and toxicity. However, studies on the difference in lithium
      levels between once and twice daily dosing, which also assess the impact of kidney function
      are scarce. The aim of this study is to quantify this pharmacokinetic difference, identify
      the impact of kidney function, in the context of estimating effects to inform feasibility and
      sample size needed for a larger well-powered study.
Bipolar disorder is a chronic and recurring condition which causes functional impairment and
      increases lifetime suicide risk. Major depressive disorder likewise confers a high burden of
      illness on the affected population, and treatment is complicated by the fact 50-70% of
      patients treated with an initial agent do not achieve full remission of symptoms. There are
      numerous clinical practice guidelines which support the use of lithium as a first-line agent
      for bipolar disorder, and as an adjunctive therapy for major depressive disorder. Therapeutic
      ranges for lithium were established in the 1970s using multiple daily dose regimens, and
      therefore should not be directly applied to patients taking lithium once daily. The current
      standard of practice is to measure levels 12 hours post dose irrespective of once or twice
      daily administration. There is some evidence that lithium levels drawn 12 hours post dose are
      10 - 26% higher when dosing lithium once daily compared to twice daily, however, the impact
      of kidney function on this difference has not been studied, and this difference in 12h post
      levels has not been confirmed via prospective data. Guidance on therapeutic drug monitoring
      (TDM) is vague with respect to interpretation of specific lithium blood levels for once daily
      dosing. Physicians may reduce a patient's dose based on a lithium level that is seemingly
      higher that target, even if the patient is clinically stable, putting the patient at risk for
      re-emergence of symptoms. Though it is known that lithium is excreted by the kidney, the
      impact of kidney function on the difference in lithium levels when dosed once daily compared
      to twice daily is not well understood. The results of this pilot study will help identify the
      impact of kidney function on lithium therapeutic drug monitoring in current practice, and
      potentially lead to a larger multi-center study.
allocation: Non-Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Difference in lithium levels between once and twice daily dosing
time frame: once 2 steady state levels have been taken (4-12 days of intervention)
description: The average of the difference in 12 hour post-dose serum level between the two dosing regimens (once daily and twice daily dosing)
measure: Correlation between renal function and difference in lithium level
time frame: once 2 steady state levels have been taken (4-12 days of intervention) and average creatinine clearance has been calculated
description: Calculated correlation coefficient (r) for renal function (as estimated by calculation of creatinine clearance via Cockroft Gault) and mean percent change in serum lithium concentration when transitioning between once and twice daily dosing
measure: Frequency of selected concurrent medication use
time frame: recorded upon enrollment, and every 4-6 days until study completion, up to 12 months
description: Frequency of thiazide diuretic, loop diuretic, NSAID, and ACE inhibitor/ARB use
arm group label: Once Daily Dosing
arm group type: Active Comparator
description: In this arm of the study, participants receive the prescribed dose of lithium once daily at bedtime. After 4-6 days, a steady state lithium serum level and serum creatinine are taken, and they crossover to the other arm (twice daily dosing, if they have not already done so). Frequency of selected medication use is noted.
arm group label: Twice Daily Dosing
arm group type: Active Comparator
description: In this arm of the study, participants receive the prescribed dose of lithium divided into two daily doses. After 4-6 days a steady state lithium serum level and serum creatinine are taken, and they crossover to the other arm (once daily dosing, if they have not already done so).Frequency of selected medication use is noted.
intervention type: Diagnostic Test
intervention name: Lithium level
description: The level of lithium in the serum
arm group label: Once Daily Dosing
arm group label: Twice Daily Dosing
intervention type: Diagnostic Test
intervention name: Serum Creatinine
description: The level of creatinine (as an indicator of kidney function, to approximate GFR) in the serum
arm group label: Once Daily Dosing
arm group label: Twice Daily Dosing
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Virginia Fernandes, PharmD
phone: 416-586-4800
email: virginia.fernandes@sinaihealthsystem.ca
last name: Dario A Moscoso, PharmD
phone: 416-586-4800
email: dario.moscoso@sinaihealthsystem.ca
facility: 
status: Recruiting
contact: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Mount Sinai Hospital, Canada
investigator full name: Virginia Fernandes
investigator title: Clinical Practice Leader, Psychiatry
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major
mesh term: Bipolar Disorder
mesh term: Lithium Carbonate
sharing ipd: No
ipd description: There is no such plan