Efficacy and Safety of Sertraline Combined With Lactobacillus Crispatus in Adolescents With Depression

Efficacy and Safety of Sertraline Combined With Lactobacillus Crispatus in Adolescents With Depression : A Multicenter Randomized Controlled Trial

The goal of this clinical trial is to evaluate the efficacy and safety of sertraline combined with Lactobacillus crispatus in adolescents aged 12-18 years with major depressive disorder. The main question it aims to answer is: Whether sertraline combined with Lactobacillus crispatus is superior to sertraline combined with placebo in reducing depressive symptoms and improving emotional symptoms in adolescents with depression.

If there is a comparison group: Researchers will compare sertraline combined with Lactobacillus crispatus with sertraline combined with placebo ( look-alike substance that contains no probiotics) to determine whether the addition of Lactobacillus crispatus provides greater therapeutic benefit in adolescents with depression.

Participants will: 1. Receive sertraline combined with Lactobacillus crispatus or sertraline combined with placebo for 8 weeks; 2. Attend clinic visits every 4 weeks for clinical assessments and safety monitoring

Study Overview

• Status: Not yet recruiting
• Conditions: Major Depressive Disorder (MDD); Probiotic Intervention
• Intervention / Treatment: Combination product: Sertraline combined with Lactobacillus crispatus; Combination product: Sertraline combined with placebo

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Teng Teng; Phone Number: +86 18883368354; Email: tengteng@hospital.cqmu.edu.cn

Study Locations

• China
  • Chongqing Municipality
    • Longgang, Chongqing Municipality, China, 404100
      • The Affiliated Dazu's Hospital of Chongqing Medical University
  • Yuzhong
    • Chongqing, Yuzhong, China, 400010
      • The Affiliated Hospital of Chongqing Medical University
      • Contact: Teng Teng; Phone Number: +18883368354; Email: tengteng@hospital.cqmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

• Aged 12-18 years
• Meets DSM-5 criteria for major depressive disorder (MDD) and is currently in a depressive episode according to the Kiddie Schedule for Affective Disorders and Schizophrenia - Present and Lifetime Version (K-SADS-PL) interviews
• Child Depression Rating Scale-Revised (CDRS-R) score ≥40 at baseline
• Clinical Global Impression Scale (CGI-S) score ≥ 4 at baseline

Exclusion criteria

• Presence of any comorbid psychiatric disorder according to DSM-5, other than anxiety disorders
• MDD with psychotic symptoms
• Young Mania Rating Scale (YMRS) >13 at baseline
• History of neurological disorders (e.g., epilepsy, traumatic brain injury), or the presence of serious physical illnesses (e.g., thyroid disease, lupus erythematosus, diabetes mellitus, clinically significant pulmonary, hepatic, or renal impairment, or major trauma)
• Nonresponse to at least two antidepressants with different mechanisms, and each administered at an adequate dose and for an adequate duration
• History of intolerance to sertraline or nonresponse to an adequate therapeutic course of sertraline
• Current high suicide risk
• History of alcohol or drug abuse or dependence
• Taking or administering antidepressants within 5 half-lives
• Use of probiotic-related food or medicine within 2 weeks before enrollment
• Systemic use of antibiotics or antifungals within 1 month before enrollment
• History of severe food allergy or known hypersensitivity to the Lactobacillus crispatus preparation or any of its components
• Adherence to vegetarian or other restrictive dietary patterns
• Pregnancy or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sertraline combined with Lactobacillus crispatus group	Combination product: Sertraline combined with Lactobacillus crispatus; Phase 1 (Weeks 1-4): Sertraline will be initiated at 25 mg/day and titrated according to clinical judgment, with a permissible dose range of 25-150 mg/day. By Week 4, the sertraline dose will reach a minimum of 150 mg/day. Concomitantly, Lactobacillus crispatus powder will be administered at 1 sachet/day (1×10⁹ CFU/sachet). Phase 2 (Weeks 5-8): Sertraline will be maintained at 150-200 mg/day, with dose adjustments guided by the psychiatrist's clinical judgment. Lactobacillus crispatus powder will remain at 1 sachet/day (1×10⁹ CFU/sachet).
Active Comparator: Sertraline combined with placebo group	Combination product: Sertraline combined with placebo; Phase 1 (Weeks 1-4): Sertraline will be initiated at 25 mg/day based on the psychiatrist's clinical assessment, with a permissible dose range of 25-150 mg/day. By Week 4, the sertraline dose will attain at least 150 mg/day, with concomitant placebo powder at 1 sachet/day. Phase 2 (Weeks 5-8): Sertraline will be maintained at 150-200 mg/day, with dose adjustments guided by the psychiatrist's clinical assessment. Placebo powder will be maintained at 1 sachet/day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Children's Depression Rating Scale - Revised (CDRS-R) scores	The Children's Depression Rating Scale-Revised (CDRS-R) is a semi-structured clinician-rated interview designed to assess the severity of depressive symptoms in children and adolescents. The total score ranges from 17 to 113, with higher scores indicating more severe depressive symptoms.	Assessments will be performed at baseline, week 4, and week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Baker Depression Scale（BDI） scores from baseline	The Beck Depression Inventory (BDI) is a self-report inventory measuring the severity of depression. It consists of 21 items with 4 answer options each. The total score ranges from 0 to 63, with higher scores indicating more severe depressive symptoms.	Assessments will be performed at baseline, week 4, and week 8
Change in the Screen for Child Anxiety-Related Emotional Disorders（SCARED）scores from baseline	The Screen for Child Anxiety-Related Emotional Disorders (SCARED) scale will be administered to assess anxiety symptoms. Responses are made on a 3-point scale: 0 = "not true or hardly ever true", 1 = "somewhat true or sometimes true," and 2 = "very true or often true". Higher total scores indicate higher levels of anxiety.	Assessments will be performed at baseline, week 4, and week 8
Change in Hamilton Anxiety Scale (HAMA）scores from baseline	The Hamilton Anxiety Scale (HAMA) will be used to assess anxiety symptoms. Responses are made on a 5-point Likert scale (0 = Not present, to 4 = Very severe). Higher total scores indicate more severe anxiety symptoms.	Assessments will be performed at baseline, week 4, and week 8
Change in suicide risk on the Columbia Suicide Severity Rating Scale (C-SSRS ) scores from baseline	The Columbia-Suicide Severity Rating Scale (C-SSRS) will be used assess the severity of suicidal ideation and suicidal behavior. It evaluates four core domains: suicidal ideation (5 items), intensity of ideation, (5-point scale), suicidal behaviors (actual, aborted, interrupted attempts, and preparatory acts), and lethality of suicide attempts. Higher scores indicate more severe suicidal ideation, and any suicidal behavior denotes elevated acute suicide risk.	Assessments will be performed at baseline, week 4, and week 8
Change in Young Mania Rating Scale (YMRS) scores from baseline	The Young Mania Rating Scale (YMRS) will be used to assess the severity of manic symptoms. It is a clinician-rated scale with 11 items. Total scores range from 0 to 60, with higher scores indicating more severe manic symptoms.	Assessments will be performed at baseline, week 4, and week 8
Changes in Ruminative Response Scale (RRS) scores from baseline	The Ruminative Response Scale (RRS) will be used to assess rumination. Responses are made on a 4-point Likert scale (1 = never to 4 = always), with total score ranges from 22 to 88. Higher scores indicate greater intensity of rumination.	Assessments will be performed at baseline, week 4, and week 8
Medication adherence	Medication adherence will be assessed by the pill count method. The adherence rate will be calculated according to the following formula: Adherence rate= (Number of dispensed tablets-Number of returned unused tablets)/ (Daily prescribed tablets × Days between two visits) ×100% Adherence ≥ 80% was defined as adequate adherence.	Assessments will be performed at week 4, and week 8
Changes in Connor-Davidson Resilience Scale (CD-RISC) scores from baseline	The Connor-Davidson Resilience Scale (CD-RISC) is used to measure psychological resilience. Responses are made on a 5-point Likert scale (0 = never to 4 = always). The total score can range from 0 to 100, with higher scores indicating greater resilience.	Assessments will be performed at baseline, week 4, and week 8
Changes in Pediatric Quality of Life Inventory™ Version 4.0 Scale (PedsQL™) scores from baseline	The Pediatric Quality of Life Inventory 4.0 generic core scales (PedsQL4.0) is a self-rated scale for assessing pediatric health-related quality of life. Responses are made on a 5-point Likert scale (1 = strongly disagree to 5 = strongly agree). Higher scores indicate better quality of life.	Assessments will be performed at baseline, week 4, and week 8
Change in Pittsburgh Sleep Quality Index (PSQI) scores from baseline	The Pittsburgh Sleep Quality Index (PSQI) will be used for evaluating subjective sleep quality. Responses are made on a 4-point Likert scale, with total score ranges from 0 to 21. Higher scores indicate poorer overall sleep quality.	Assessments will be performed at baseline, Week 4, and Week 8
Changes in Gastrointestinal Symptom Rating Scale (GSRS) scores from baseline	The Gastrointestinal Symptom Rating Scale (GSRS), a self-rated questionnaire, will be used to assess the severity of gastrointestinal symptoms. Responses are made on a 7-point Likert scale (1 = not at all to 7 = extremely severe). Higher scores indicate more severe gastrointestinal symptoms.	Changes from baseline to week 4 and week 8
Changes in Childhood Trauma Questionnaire (CTQ) scores from baseline	The Childhood Trauma Questionnaire (CTQ) will be used to assess childhood trauma. Responses were made on a 5-point Likert scale (1 = never to 5 = always). Higher scores indicate greater frequency and severity of child maltreatment experiences.	Assessments will be performed at baseline, week 4, and week 8
Changes in Clinical Global Impressions - Severity (CGI-S) scores from baseline	The Clinical Global Impressions-Severity (CGI-S), a clinician-rated outcome measure, was used to evaluate the overall severity of depressive symptoms. Higher CGI-S scores represent more severe overall illness.	Assessments will be performed at baseline, week 4, and week 8
Changes in Clinical global impressions-improvement (CGI-I) scores from baseline	The Clinical Global Impressions-Improvement (CGI-I) is an 8-point clinician-rated scale ranging from 0 to 7, which will be used to assess the overall improvement in depressive symptoms compared with baseline. Lower scores indicate greater clinical improvement.	Assessments will be performed at baseline, week 4, and week 8

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Chongqing Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: April 14, 2026
• First Submitted That Met QC Criteria: April 14, 2026
• First Posted (Actual): April 20, 2026

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: zz2025-535-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No