Lithium Therapeutic Drug Monitoring; Once Daily Vs Twice Daily Dosing and the Impact of Kidney Function

Major Depressive Disorder Clinical Trial

Official title:

Lithium Therapeutic Drug Monitoring; Once Daily Vs Twice Daily Dosing and the Impact of Kidney Function

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03811860
• Other study ID #: 18-0289-A
• Status: Recruiting
• Phase: N/A
• Start date: February 6, 2019
• Est. completion date: December 2019

Study information

• Verified date: March 2019
• Source: Mount Sinai Hospital, Canada
• Contact: Virginia Fernandes, PharmD
• Phone: 416-586-4800
• Email: virginia.fernandes[@]sinaihealthsystem.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: December 2019
• Est. primary completion date: September 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients admitted to the inpatient psychiatry unit at Mount Sinai Hospital treated with lithium therapy (i.e. taking lithium before admission, or initiated on lithium therapy during hospitalization)

Exclusion Criteria:

• any patients who are currently pregnant

• patients taking lithium three times daily

• patients taking lithium with a specific dosing frequency for a documented clinical reason.

Related Conditions & MeSH terms

• Bipolar Disorder
• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Disease
• Major Depressive Disorder

Intervention

Diagnostic Test:
• Lithium level
The level of lithium in the serum
• Serum Creatinine
The level of creatinine (as an indicator of kidney function, to approximate GFR) in the serum

Locations

Country	Name	City	State
Canada	Mount Sinai Hospital	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Mount Sinai Hospital, Canada

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in lithium levels between once and twice daily dosing	The average of the difference in 12 hour post-dose serum level between the two dosing regimens (once daily and twice daily dosing)	once 2 steady state levels have been taken (4-12 days of intervention)
Secondary	Correlation between renal function and difference in lithium level	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	once 2 steady state levels have been taken (4-12 days of intervention) and average creatinine clearance has been calculated
Secondary	Frequency of selected concurrent medication use	Frequency of thiazide diuretic, loop diuretic, NSAID, and ACE inhibitor/ARB use	recorded upon enrollment, and every 4-6 days until study completion, up to 12 months