Utility of Plasma Drug Level Monitoring and CYP2C19 Genotyping in Dose Personalization of Sertraline
Trial Snapshot
- Phase
- Not Applicable
- Status
- Withdrawn
- Sponsor
- University of Belgrade
- Enrollment
- 148
- Locations
- 3
- Primary Endpoint
- Change from Baseline Depression severity score at week 8
Study Overview
Brief Summary
The aims of this study are to:
- Determine the proportion of participants who are underdosed or overdosed under recommended dosing regimen of sertraline for the depression treatment (100 mg/day)
- Determine and quantify clinical benefits of personalized sertraline dosing regimen based on the sertraline blood level monitoring
- Retrospectively estimate whether the information on CYP2C19 genotype is useful in prediction of sertraline blood level.
Detailed Description
Sertraline is an antidepressant extensively metabolized by the polymorphic CYP2C19 enzyme. Based on CYP2C19 genotype, patients can be classified as:
- Normal metabolizers (Normal CYP2C19 enzyme capacity)
- Intermediate metabolizers (Decreased CYP2C19 enzyme capacity)
- Poor metabolizers (No CYP2C19 enzyme capacity)
- Ultra rapid metabolizers (Increased CYP2C19 enzyme capacity)
Adequate sertraline exposure is needed to achieve optimal clinical response in the treatment of depression: too low drug plasma levels can lead to the lack of pharmacological effect, whereas too high drug plasma levels increases the incidence of adverse effects. There is evidence that patients with variant CYP2C19 genotypes have abnormal sertraline exposure and could benefit from sertraline dose personalization, but precise evidence-based protocol for personalized dosing of sertraline has not been developed yet. This multicentric observational clinical trial is designed to collect crucial information for the development of such protocol that will be based on drug plasma level monitoring and/or CYP2C19 genotyping.
Course of the study will be as follows:
Initial Visit (V0):
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to 60 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Diagnosed Major Depressive Disorder
- •Starting monotherapy with sertraline
- •Signed written informed consent
Exclusion Criteria
- •Patient's requests to leave the study
- •Patients who had taken sertraline before
- •Severe liver function impairment (abnormal AST/ALT ratio)
- •Severe kidney function impairment (abnormal creatinine clearance)
- •History of drug addiction (sporadic use is permitted)
- •Suicide risk
- •Patients who are taking strong CYP2C19 inhibitors
- •Severe adverse drug reaction
Arms & Interventions
Standard dose
Patients are allocated to this group at visit V1 if 100 mg/day sertraline dose resulted in optimal sertraline exposure (20-40 ng/ml) as measured at VK. These patients continue to be treated with 100 mg/day during the V1-V2 period.
Intervention: Sertraline (Drug)
Adjusted dose
Patients are allocated to this group at visit V1 if 100 mg/day sertraline dose resulted in high (>40 ng/ml) or low (<20 ng/ml) sertraline exposure, as measured at VK. These patients continue to be treated with the adjusted sertraline dose, different from 100 mg/day, during the V1-V2 period.
Intervention: Sertraline (Drug)
Outcomes
Primary Outcomes
Change from Baseline Depression severity score at week 8
Time Frame: 8 Weeks
Measured with clinician reported 21-item Hamilton rating scale for depression (HAM-D). Scale gives a score from 0 to 52 where higher score represents higher depression severity and worse outcome.
Adverse drug reaction severity score at week 8
Time Frame: 8 Weeks
Measured with clinician reported UKU (Udvalg for Kliniske Undersogelser) side effect rating scale. Scale gives summary score from 0 to 3 where higher scores correspond to the greater side-effects severity and worse outcome.
Secondary Outcomes
- Adverse drug reaction severity score at week 4(4 Weeks)
- Number of participants with sertraline plasma concentrations outside the therapeutic window(at Week 2)
- Retrospectively determined regression formula for prediction of sertraline plasma levels at Vk based on CYP2C19 metabolizer status(8 Weeks)
- Change from Baseline Depression severity score at week 4(4 Weeks)
Investigators
Marin Jukic
Assistant Professor, PhD
University of Belgrade