Personalized Sertraline Dosing in Patients With Depression

NCT05210153 | Unknown DMC FDA Drug

• 1 other identifier: 6066800-S
• Study Type: observational
• Target: 148
• Locations: 1 country
• Sites: 3

Brief Summary

The aims of this study are to:

1. 1.Determine the proportion of participants who are underdosed or overdosed under recommended dosing regimen of sertraline for the depression treatment (100 mg/day)
2. 2.Determine and quantify clinical benefits of personalized sertraline dosing regimen based on the sertraline blood level monitoring
3. 3.Retrospectively estimate whether the information on CYP2C19 genotype is useful in prediction of sertraline blood level.

Conditions

Depressive Disorder, Major

Keywords

Sertraline; Cytochrome p 450 cyp2c19; Precision medicine; Psychiatry; Pharmacogenetics; Serotonin Uptake Inhibitors

Outcome Measures

Primary Outcomes (2)

• Change from Baseline Depression severity score at week 8

  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.

  8 Weeks

• Adverse drug reaction severity score at week 8

  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.

  8 Weeks

Secondary Outcomes (4)

• 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

• Adverse drug reaction severity score at week 4

  4 Weeks

Other Outcomes (23)

• Perception of stress score at baseline

  Baseline

• Perception of stress score at week 4

  4 Weeks

• Perception of stress score at week 8

  8 Weeks

Study Arms (2)

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.

Drug: Sertraline

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.

Drug: Sertraline

Interventions

Sertraline DRUG

Drug: Sertraline, a selective serotonin reuptake inhibitor (SSRI), is commercially known as Sidata® or Zoloft® in Serbia. The recommended dose for Major depressive disorder is 100 mg/day. It is recommended to start therapy with 50 mg/day, and in the case of lack of therapeutic effect dose should be increased in 50 mg increments every 2 weeks until intended pharmacological effect is reached. Dose can be increased up to the maximum dose is 200 mg/day. Sertraline is also indicated for treatment of Obsessive-compulsive disorder, Generalized anxiety disorder, Social anxiety disorder (Social phobia), Panic disorder (with or without agoraphobia) and Post-traumatic Stress Disorder by Medicines and Medical Devices Agency of Serbia. Drug levels are expected to be 50% higher in CYP2C19 poor metabolizers as compared to normal metabolizers, but no specific dosing recommendations are given by the Medicines and Medical Devices Agency of Serbia.

Also known as: Zoloft, Lustral

Adjusted dose; Standard dose

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Study population includes outpatients suffering from Major Depressive disorder who are previously untreated, and are seeking medical help for the first time.

You may qualify if:

• Diagnosed Major Depressive Disorder
• Starting monotherapy with sertraline
• Signed written informed consent

You may not qualify if:

• Patient's requests to leave the study
• Patients who had taken sertraline before
• Dementia
• 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

Sponsors & Collaborators

• University of Belgrade: lead
• Clinical Centre of Serbia: collaborator
• Institute of Mental Health, Serbia: collaborator
• Military Medical Academy, Belgrade, Serbia: collaborator

Study Sites (3)

Clinical Centre of Serbia

Belgrade, 11000, Serbia

RECRUITING

Institute of Mental Health

Belgrade, 11000, Serbia

RECRUITING

Military Medical Academy

Belgrade, 11000, Serbia

NOT YET RECRUITING

Related Publications (3)

• Pennebaker JW, Susman JR. Disclosure of traumas and psychosomatic processes. Soc Sci Med. 1988;26(3):327-32. doi: 10.1016/0277-9536(88)90397-8.

  PMID: 3279521 BACKGROUND

• Braten LS, Haslemo T, Jukic MM, Ingelman-Sundberg M, Molden E, Kringen MK. Impact of CYP2C19 genotype on sertraline exposure in 1200 Scandinavian patients. Neuropsychopharmacology. 2020 Feb;45(3):570-576. doi: 10.1038/s41386-019-0554-x. Epub 2019 Oct 24.

  PMID: 31649299 BACKGROUND

• Milosavljevic F, Bukvic N, Pavlovic Z, Miljevic C, Pesic V, Molden E, Ingelman-Sundberg M, Leucht S, Jukic MM. Association of CYP2C19 and CYP2D6 Poor and Intermediate Metabolizer Status With Antidepressant and Antipsychotic Exposure: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2021 Mar 1;78(3):270-280. doi: 10.1001/jamapsychiatry.2020.3643.

  PMID: 33237321 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Two ml of plasma for the measurement of drug concentrations at visits at week 2, week 4 and week 8. Two ml of serum for biochemical analyses of liver and kidney function, cortisol levels, lipid status and glucose levels at visits at week 2, week 4 and week 8. "Buffy coat" taken from the 5 ml blood sample for DNA extraction and CYP2C19 genotyping, at any visit.

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Sertraline

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

1-Naphthylamine; Amines; Organic Chemicals; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Central Study Contacts

Marin M Jukić, PhD

CONTACT

+381 11 3951 314; marin.jukic@pharmacy.bg.ac.rs

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, PhD

Study Record Dates

• First Submitted: December 21, 2021
• First Posted: January 27, 2022
• Study Start: July 16, 2020
• Primary Completion: September 1, 2023
• Study Completion: November 1, 2023
• Last Updated: November 8, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Starting from the time of publication of the main summary study results.
• Access Criteria: IPD will be accessible to everyone.

Locations

SE (3)