Sertraline for Bipolar depression

Inclusion criteria

• {"criterion_text":"- In- or out patients, at least 18 years of age."}
• {"criterion_text":"- Being willing and able to provide written informed consent. Having a legal guardian to cosign is allowed. Informed consent will be signed at visit 1, before any study procedure."}
• {"criterion_text":"- Female participants of child bearing potential must use effective contraception during the trial as per the requirements of the applicable SmPCs and should have a negative pregnancy test at visit 1 or 2 (before randomisation; section 8.2.1). Male subjects that will use valproate acid during the trial must use effective contraceptive measures during the trial (see section 8.2.1)."}
• {"criterion_text":"- Meeting diagnostic criteria for a primary diagnosis of bipolar depression (bipolar disorder type I and II currently in a depressive episode), according to DSM-5. The primary diagnosis will be confirmed by the Mini International Neuropsychiatric Interview (MINI v7.0.2)."}
• {"criterion_text":"- Participant experiences a current treatment failure due to lack of efficacy, as confirmed by a CGI-I ≥3; preferably this treatment is a first-line pharmacotherapeutic agent for the primary DSM-5 diagnosis, and was prescribed for at least 4 weeks within an effective dose range as specified in the Summary of Product Characteristics (SmPCs). However, other treatments are accepted as long as they are in line with clinical guidelines and protocols for BD."}
• {"criterion_text":"- Participant and clinician intend to change pharmacotherapeutic treatment."}
• {"criterion_text":"- A minimum symptom severity threshold needs to be present (moderate level; see below) and participant needs to experience functional impairment. - The minimum symptom severity threshold is a score of ≥20 on the Montgomery Åsberg Depression Rating Scale (MADRS). - Functional impairment is defined as a score of 5 or higher on any of the three scales of the Sheehan Disability Scale (SDS)."}

Exclusion criteria

• {"criterion_text":"- Being pregnant or breastfeeding."}
• {"criterion_text":"- Participant has a known intolerance to quetiapine or to all EIPT medication or to all TAU medication."}
• {"criterion_text":"- Meeting any of the contraindications for quetiapine, or to all EIPT medication or to all TAU medication options, as specified within the applicable SmPC, supported by clinically significant abnormal values on local laboratory tests, electrocardiogram (ECG) or physical examinations."}
• {"criterion_text":"- Participant has participated in another clinical trial in which the subject received an experimental or investigational drug or agent within 30 days before visit 1."}
• {"criterion_text":"- Participant experiences any other significant disease or disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial."}
• {"criterion_text":"- Participants with active suicidal ideation with some intent to act, without specific plan (“Yes” to question 4 of the Columbia-Suicide Severity Rating Scale (C-SSRS)) or active suicidal ideation with specific plan and intent (“Yes” to question 5 of the C-SSRS), followed by an assessment by the treating clinician who determines it is not safe for the subject to participate in the study."}
• {"criterion_text":"- Participants meet criteria for current substance use disorder, as confirmed by the Mini International Neuropsychiatric Interview (MINI v7.0.2). Nicotine dependency is allowed, as well as mild and moderate alcohol and/or cannabis use disorder (as defined by MINI v7.0.2). Severe alcohol and/or cannabis use disorder are not allowed."}
• {"criterion_text":"- Participants dependent on the sponsor, investigator or trial site must be excluded from participation in advance."}
• {"criterion_text":"- Participants with pre-existing severe liver damage (as tested within the local laboratory test at visit 1)."}
• {"criterion_text":"- Participants with a history of antidepressant‐induced mania or hypomania or recent rapid cycling (based on the medical file of the potential participant or the clinical judgment of the clinician)."}
• {"criterion_text":"- Participants have not been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities."}
• {"criterion_text":"- A score of 12 or higher on the Young Mania Rating Scale (YMRS) in order to exclude participants with predominant manic symptoms or mixed symptoms."}

Primary endpoints

• {"endpoint_text":"- Mean change from baseline (visit 2) in symptom severity as measured by the MADRS total score at six weeks (visit 4) will be compared between the two treatment arms (EIPT vs. TAU) for the lines of treatment separately (subgroup analysis wherein the focus will be on participants who had a first time treatment failure on their first-line treatment) and for the group as a whole (irrespective of line of treatment).","definition_or_measurement_approach":"Mean change from baseline (visit 2) in symptom severity measured by the MADRS total score at six weeks (visit 4); comparison between EIPT and TAU overall and in subgroup of first-line treatment failure."}

Secondary endpoints

• {"endpoint_text":"- 1.a. Change from baseline (visit 2) in the severity sub-score of the Clinical Global Impression Scale (CGI) at visit 4; EIPT vs TAU. 1.b. Improvement sub-score of the Clinical Global Impression Scale (CGI) at visit 4; EIPT vs TAU.","definition_or_measurement_approach":"CGI severity and improvement sub-scores at visit 4 compared between arms."}
• {"endpoint_text":"- Changes from baseline (visit 2) in total Hospital Anxiety and Depression Scale (HADS) total score and anxiety and depression subscales at visit 4; EIPT vs TAU.","definition_or_measurement_approach":"HADS total and subscale scores at visit 4 compared between arms."}
• {"endpoint_text":"- Change from baseline (visit 2) in quality of life and functioning measures (Q-LES-Q-SF, LAPS, QLS-100 and SDS ) at visit 4; EIPT vs TAU.","definition_or_measurement_approach":"Changes in Q-LES-Q-SF, LAPS, QLS-100 and SDS at visit 4 compared between arms."}
• {"endpoint_text":"- Changes from baseline (visit 2) on Trail Making Test, Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test as well as the Perceived Deficits Questionnaire at visit 4; EIPT vs TAU.","definition_or_measurement_approach":"Neurocognitive tests (TMT, DSST, RAVLT) and PDQ at visit 4 compared between arms."}
• {"endpoint_text":"- Presence of symptomatic remission at visit 4; EIPT vs TAU. Remission is defined as a MADRS score ≤ 12.","definition_or_measurement_approach":"Remission defined as MADRS ≤ 12 assessed at visit 4; compare proportions between arms."}
• {"endpoint_text":"- Presence of reported adverse events (related and unrelated to treatment) as measured through General Assessment of Side Effects Scale (GASE) and reported spontaneously at visit 4; EIPT vs TAU.","definition_or_measurement_approach":"Adverse events captured via GASE and spontaneously reported; compare incidence between arms."}
• {"endpoint_text":"- Concomitant medication use throughout the study; EIPT vs TAU.","definition_or_measurement_approach":"Recording and comparison of concomitant medication use across study duration between arms."}
• {"endpoint_text":"- Premature treatment discontinuation before visit 4 and time to treatment discontinuation and reported reason of discontinuation; EIPT vs TAU.","definition_or_measurement_approach":"Time to and reasons for treatment discontinuation before visit 4 compared between arms."}
• {"endpoint_text":"- Changes on the Columbia-Suicide Severity Rating Scale (C-SSRS) throughout the study; EIPT vs TAU.","definition_or_measurement_approach":"C-SSRS scores tracked over the study; compare changes between arms."}
• {"endpoint_text":"- Occurrence of (hypo)manic episodes throughout the study (including V5); EIPT vs TAU. Scores of 12 or higher means that a participant is in a (hypo)manic episode of bipolar disorder.","definition_or_measurement_approach":"Occurrence of (hypo)manic episodes defined by YMRS ≥ 12 across study visits; compare between arms."}

Methods

• Italy: recruitment arrangements and poster materials (documents: K1_Recruitment arrangements_Italy; K2_Recruitment Material_Poster_Italy)
• Austria (Innsbruck): recruitment arrangements and posters (documents: K1_Recruitment Arrangements_02_Innsbruck; K2_Recruitment Material_Poster_BD_German)
• Germany: recruitment arrangements, posters, flyers and website text (documents: K1_Recruitment arrangements_Germany; K2_Recruitment Material_Poster; K2_Recruitment Material_Flyer_08_Munster; K1_Recruitment arrangements website text_07_Mainz)
• Greece (Athens): recruitment arrangements (document: K1_Recruitment Arrangements_Athens_16)
• Spain (Barcelona): recruitment arrangements and poster materials (documents: K1_Recruitment arrangements_14_Barcelona; K2_Recruitment material poster_14_Barcelona)
• Use of GP letters and patient cards for recruitment/participant information (documents: L2_Other information material_GP letter_redacted; L2_Other subject information_Patient card_Italy and equivalents per country)

Italy

Earliest CTIS Part Ii Submission Date

19-10-2023

Latest Decision Or Authorization Date

08-01-2026

Processing Time Days

812

Number Of Sites

4

Number Of Participants

130

Greece

Earliest CTIS Part Ii Submission Date

27-11-2024

Latest Decision Or Authorization Date

08-01-2026

Processing Time Days

407

Number Of Sites

1

Number Of Participants

35

Austria

Earliest CTIS Part Ii Submission Date

28-11-2023

Latest Decision Or Authorization Date

29-12-2025

Processing Time Days

762

Number Of Sites

1

Number Of Participants

25

Germany

Earliest CTIS Part Ii Submission Date

12-12-2023

Latest Decision Or Authorization Date

30-12-2025

Processing Time Days

749

Number Of Sites

5

Number Of Participants

145

Spain

Earliest CTIS Part Ii Submission Date

10-12-2023

Latest Decision Or Authorization Date

05-01-2026

Processing Time Days

757

Number Of Sites

1

Number Of Participants

15

Primary sponsor

Full Name

Universitair Medisch Centrum Utrecht

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Contract research organisations

Name

Kairos

Responsibilities

[code 7]

Name

Castor EDC

Responsibilities

Randomisation module

Third parties

• {"country":"Germany","full_name":"Fraunhofer-Institut für Algorithmen und Wissenschaftliches","duties_or_roles":"[code 7]","organisation_type":"Industry"}
• {"country":"Germany","full_name":"Kairos","duties_or_roles":"[code 7]","organisation_type":"Industry"}
• {"country":"Netherlands","full_name":"Castor EDC","duties_or_roles":"Randomisation module","organisation_type":"Industry"}
• {"country":"Germany","full_name":"Ludwig Maximilian University Of Munich","duties_or_roles":"Laboratory Management","organisation_type":"Educational Institution"}