Sequenced Treatment in Adolescents With Major Depression (STAMD): a Multicenter Open-label Randomized Controlled Trial

Sponsor

First Affiliated Hospital of Chongqing Medical University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05814640

Collaborator

Second Xiangya Hospital of Central South University (Other)

520

Enrollment

Location

Arms

52.3

Anticipated Duration (Months)

9.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of this project is to investigate the effectiveness of existing common antidepressants and to provide new evidence for depressed children and adolescents who are not responding to their first treatment.

Condition or Disease	Intervention/Treatment	Phase
Depression Sequestra	Drug: Fluoxetine Drug: Sertraline Drug: Vortioxetine Drug: Duloxetine Drug: Aripiprazole Drug: Lithium Carbonate Drug: Olanzapine Behavioral: GCBT	Phase 1/Phase 2

Detailed Description

This is a open-label Sequential Multiple Assignment Randomized Trial (SMART) of 16 weeks duration with two levels of randomization, one in each of two 8-week stages. Stage1 is a randomized controlled trial; patients will be randomly assigned to one of the treatments with fluoxetine or combination. Subjects who fail to respond will enter the phase 2 randomization，where patients will be randomly assigned to oral sertraline, votioxetine, duloxetine or adding one of aripiprazole, lithium carbonate, and olanzapine to fluoxetine. The primary outcome for the treatment phase is the treatment remission rate and response rate. Secondary outcomes included: symptom scale; Quality of life; Sleep therapy; Symptoms of anxiety; Rumination and safety assessment.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

520 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

After receiving a specific drug and drug linkage therapy, the next stage of treatment is determined by the patient's response (efficacy and adverse reactions) and is scheduled according to the patient's wishes and random assignment.After receiving a specific drug and drug linkage therapy, the next stage of treatment is determined by the patient's response (efficacy and adverse reactions) and is scheduled according to the patient's wishes and random assignment.

Masking:

Double (Investigator, Outcomes Assessor)

Masking Description:

Both the patient and the psychiatrist know which group they are allocated to, while the outcome assessor and data analyst are kept blind to the allocation. The clinicians providing the intervention do not perform the assessment and are unaware of the results.

Primary Purpose:

Treatment

Official Title:

Sequenced Treatment in Adolescents With Major Depression (STAMD): a Multicenter Open-label Randomized Controlled Trial

Actual Study Start Date :

Feb 20, 2023

Anticipated Primary Completion Date :

Dec 31, 2025

Anticipated Study Completion Date :

Jul 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fluoxetine Dosage form: po Dosage: 10-60mg Frequency :qn Course of treatment: 8 weeks. At week 8, patients will be evaluated as "in remission" or "not in remission." "Patients who are not in remission" will be randomized to phase II treatment.	Drug: Fluoxetine Commonly used oral antipsychotics intervention therapy.
Experimental: group cognitive behavioral therapy（GCBT） GCBT was administered in addition to fluoxetine and consisted of 11 sessions for 8 weeks. It lasts 90 to 120 minutes, once or twice a week. At week 8, patients will be evaluated as "in remission" or "not in remission." "Patients who are not in remission" will be randomized to phase II treatment.	Behavioral: GCBT Commonly used intervention therapy of psychotherapy.
Experimental: Sertraline dosage form: po dosage:25-200mg frequency:qn duration: At Week 8, patients assessed as 'non-remission' will be given Sertraline as an switching treatment to fluoxetine.	Drug: Sertraline Commonly used oral antipsychotics intervention therapy.
Experimental: Votioxetine dosage form:po dosage:10-20mg frequency:qn duration: At Week8, patients assessed as 'non-remission' will be given votioxetine as an switching treatment to fluoxetine.	Drug: Vortioxetine Commonly used oral antipsychotics intervention therapy.
Experimental: Duloxetine dosage form: po dosage: 60-120mg frequency: qn duration: At Week 8, patients assessed as 'non-remission' will be given duloxetine as an add-on treatment to fluoxetine.	Drug: Duloxetine Commonly used oral antipsychotics intervention therapy.
Experimental: Aripiprazole dosage form: po dosage:2.5-15mg frequency:qn duration:At Week 8, patients assessed as 'non-remission' will be given aripiprazole as an add-on treatment to fluoxetine.	Drug: Aripiprazole Commonly used oral antipsychotics intervention therapy.
Experimental: Lithium carbonate dosage form:po dosage: 125-500mg frequency: qn duration: At Week 8, patients assessed as 'non-remission' will be given lithium carbonate as an add-on treatment to fluoxetine.	Drug: Lithium Carbonate Commonly used oral antipsychotics intervention therapy.
Experimental: Olanzapine dosage form:po dosage: 1.25-10mg frequency:qn duration: At Week 8, patients assessed as 'non-rremission' will be given olanzapine as an add-on treatment to fluoxetine.	Drug: Olanzapine Commonly used oral antipsychotics intervention therapy.

Outcome Measures

Primary Outcome Measures

Change in CDRS-R (Children's Depression Rating Scale) scores from baseline [Baseline of treatment period, 2 weeks, 1 month, 2 months, 3 months，4months; The follow-up period was 1 month, 3 months, 6 months and 12 months]
Clinical response (≥ 50% reduction in CDRS-R scores from baseline)

Secondary Outcome Measures

Change in BDI-II (Baker Depression Scale) scores from baseline [Baseline of treatment period, 1 month, 2 months, 3 months，4 months; The follow-up period was 1 month, 3 months, 6 months and 12 months]
Change in BDI-II (Baker Depression Scale) scores from baseline
Change in SCARED (The Screen for Child Anxiety-Related Emotional Disorders) scores from baseline [Baseline of treatment period, 1 month, 2 months, 3 months，4 months; The follow-up period was 1 month, 3 months, 6 months and 12 months]
Improvement in anxiety (SCARED minus the scores）
Change in suicide risk from baseline on the C-SSRS (Columbia Suicide Severity Rating Scale) [Baseline of treatment period, 1 month, 2 months, 3 months，4 months; The follow-up period was 1 month, 3 months, 6 months and 12 months]
The severity of the suicide risk
Change in PSQI (Pittsburgh Sleep Quality Index) scores from baseline [Baseline of treatment period, 2 month, 4 months; The follow-up period was 1 month, 3 months, 6 months and 12 months]
Improvement in sleep status (PSQI minus the scores）
Change in PedsQL4.0 (The Pediatric Quality of Life Inventory) scores from baseline [Baseline of treatment period, 2 month, 4 months; The follow-up period was 1 month, 3 months, 6 months and 12 months]
Improvement of children's quality of life（PedsQL4.0 minus the scores)
Change in CGI-S (Clinical Global Impressions-Severity Scales) scores from baseline [Baseline of treatment period, 1 month, 2 months, 3 months，4 months.]
Improvement in overall clinical impression severity
Change in CGI-I (Clinical Global Impressions-Improvement Scales) scores from baseline [The treatment period was 1 month, 2 months, 3 months，4 months.]
Improvement of clinical general Impression scale
Change in RSS (Ruminative Responses Scale) [The treatment period was 1 month, 2 months.]
The level of improvement in negative thinking
Change in HCL-32（Hypomania Symptom Checklist-32） [Baseline of treatment period, 1 month, 2 months, 3 months，4 months; The follow-up period was 1 month, 3 months, 6 months and 12 months]
Assess the patient's hypomanic state

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 13 - 18
As assessed by K-SADS-PL, it meets the DSM-V criteria for MDD with non-psychotic symptoms
Score≥40 on the CDRS-R
Participants with suicidal ideation are eligible, as long as clinicians consider outpatient treatment to be safe
Sufficient audio-visual level to complete this study
Written informed consent was obtained from patients and at least one of their parents

Exclusion Criteria:

History of bipolar disorder, schizophrenia, autism, eating disorders, primary obsessive compulsive disorder, pervasive developmental disorder, or psychosis not otherwise specified
History of serious physical illnesses
Substance abuse or dependence
Current depressive episode with clear suicidal plans or suicidal behavior
Requires inpatient treatment for psychiatric disorders
Severe mental disorders requiring
2 or more failed trials of antidepressant drugs: each trial for at least 8 weeks, with the last 4 weeks at full dose (e.g. fluoxetine 40mg/d, citalopram 40mg/d, escitalopram 20mg/d, sertraline 150mg/d )
History of clear-cut intolerability of, or lack of effect with, an adequate trial of at least one protocol treatment option
Taking any medicine that contraindicates in combination with or interferes with the efficacy of the treatment
Taking or administering antidepressants within 5 half-lives
Received modified electroconvulsive therapy within 12 months
If female, is pregnant