Smartphone-Delivered Cognitive Behavioral Digital Therapeutic for Children and Adolescents With Major Depressive Disorder: Protocol for a Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

JMIR Res Protoc. 2026 Nov 13;15:e103430. doi: 10.2196/103430.

ABSTRACT

BACKGROUND: Depression is a leading contributor to morbidity and disability in children and adolescents. Cognitive behavioral therapy (CBT) is a guideline-recommended first-line treatment, but access is constrained by therapist supply, distance, and stigma. Internet-based CBT is a scalable adjunct in adults, yet regulatory-grade evidence in Chinese pediatric samples remains limited.

OBJECTIVE: This trial will determine whether a smartphone-delivered CBT-based digital therapeutic is superior to a matched health-education placebo in reducing depressive symptoms in Chinese children and adolescents with major depressive disorder (MDD), and characterize its safety.

METHODS: This is a prospective, multicenter, double-blind, placebo-controlled superiority trial at 4 tertiary-A hospitals in mainland China. Children and adolescents aged 8-17 years meeting DSM-5 (Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition]) criteria for current MDD without psychotic features and scoring above 30 on the Children’s Depression Rating Scale-Revised (CDRS-R) at screening will be randomized 1:1 to the investigational digital therapeutic (Model WL-PD) or a visually matched health-education placebo. Both arms receive 8 weeks of structured content on an identical schedule; participants with CDRS-R ≥57 additionally receive open-label fluoxetine under weight-banded dosing. The primary end point is CDRS-R total-score reduction from baseline to week 8. Secondary end points include CDRS-R change at weeks 1 to 6; response and remission rates; Clinical Global Impression scores; the Children’s Depression Inventory; the Conners’ Parent Symptom Questionnaire; and a week-8 device-performance evaluation. Safety end points include adverse-event, serious adverse-event, and device-defect incidence. The planned sample of 214 participants (107 per arm) is powered at 80% to detect a between-arm difference of 4.6 CDRS-R points (assumed control SD 10.7) with a 1-sided α of .025 and 20% inflation for attrition. The primary analysis is an analysis of covariance on the full analysis set adjusting for baseline CDRS-R, severity category, fluoxetine exposure, and site; superiority is declared if the lower bound of the 2-sided 95% CI excludes zero, with a mixed model for repeated measures as a sensitivity analysis.

RESULTS: The trial opened to enrollment in March 2026; recruitment is ongoing, with a planned close in December 2026. The last week-8 visit is expected in the first quarter of 2027, and the primary analysis the following year.

CONCLUSIONS: The trial addresses 3 recognized gaps in the pediatric digital therapeutics literature: a rigorous, structurally matched blinded control condition, recruitment beyond a single site, and integration of guideline-concordant pharmacotherapy. Because recruitment is confined to tertiary hospitals and excludes participants with prominent suicidality or comorbidity, findings will apply to supervised use in specialist services rather than unselected community care.

TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2600120453; https://tinyurl.com/3xzaajhp.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/103430.

PMID:43024878 | DOI:10.2196/103430