Efficacy, Safety, and Acceptability of Internet-based Cognitive Behavioral Therapy

NCT05554289 | Completed

• 1 other identifier: ICBT2021
• Study Type: interventional
• Target: 315
• Locations: 1 country
• Sites: 11

Brief Summary

This is a prospective, randomized, multicenter, double-blind, placebo-controlled phase III trial evaluating the efficacy and safety of WL-iCBT - a smartphone-based digital therapeutic combining cognitive behavioral therapy and attention bias modification. The study enrolls 315 participants aged 18-60 with mild-to-moderate MDD (MADRS score 18-30) across 11 clinical centers in China. Participants will be randomized to receive either active WL-iCBT or placebo software for 8 weeks, followed by a 26-week observational extension phase. Primary endpoint is change in MADRS score from baseline to Week 8. Secondary endpoints include treatment response rate, remission rate, anxiety symptoms (HAMA), functional impairment (SDS), and cognitive function (PDQ-D), and Clinical Global Impression rating scale (CGI). Safety monitoring includes AE/SAE recording and device deficiency assessment. Acceptability will be assessed by device performance evaluation.

Conditions

Depression

Keywords

Cognitive behavioral therapy; Cognitive bias modification; Digital therapeutics

Outcome Measures

Primary Outcomes (1)

• Change in Montgomery-Asberg Depression Rating Scale (MADRS) Score

  Improvement in MADRS total score 8 weeks from baseline. MADRS is a clinician-rated scale that measures the severity of depressive symptoms. The scale consists of 10 items, each rated 0-6, with a total score range of 0-60. Higher scores indicate more severe depression symptoms. A decrease in score represents improvement.

  Week 8 (end of treatment)

Secondary Outcomes (10)

• MADRS Treatment Response Rate

  Week 4, Week 8 (end of treatment), and Week 34 (26 weeks post-treatment)

• MADRS Remission Rate

  Week 4, Week 8 (end of treatment), and Week 34 (26 weeks post-treatment)

• Change in Montgomery-Asberg Depression Rating Scale (MADRS) Score

  Week 4 (end of treatment) and Week 34 (26 weeks post-treatment)

• Change in Hamilton Anxiety Scale (HAMA) Score

  Week 4, Week 8 (end of treatment), and Week 34 (26 weeks post-treatment)

• Change in Clinical Global Impression (CGI) Score

  Week 4, Week 8 (end of treatment), and Week 34 (26 weeks post-treatment)

Study Arms (2)

Depression Auxiliary Intervention Treatment Software (WL-iCBT)

EXPERIMENTAL

Participants in this arm receive the Depression Auxiliary Intervention Treatment Software (WL-iCBT) for 8 weeks. The software employs mobile-based cognitive behavioral therapy through a smartphone interface with structured interactive multimedia content. Participants use the software once daily for 10-15 minutes, completing 56 sessions over the 8-week treatment period. The intervention consists of eight progressive modules covering rational understanding of depression, methods for regulating negative emotions, and cognitive behavioral training. The software also includes attention bias modification training through "Finding Pleasure" and "Positive Action" exercises. Following the 8-week treatment period, participants enter the 26-week observational follow-up phase with no continued intervention from the study.

Device: Depression Auxiliary Intervention Treatment Software (WL-iCBT)

Placebo Control Software (WL-iHE)

PLACEBO COMPARATOR

Participants in this arm receive a placebo control version of the software (WL-iHE) for 8 weeks. The control software mimics the appearance and usage pattern of the active intervention but lacks the therapeutic cognitive behavioral therapy components. Participants use the software once daily for 10-15 minutes, completing 56 sessions over the 8-week treatment period. The control software has the same user interface and time requirements as the active intervention but does not deliver the structured cognitive behavioral therapy content or attention bias modification training. Following the 8-week treatment period, participants enter the 26-week observational follow-up phase with no continued intervention from the study.

Device: Placebo Control Software (WL-iHE)

Interventions

Depression Auxiliary Intervention Treatment Software (WL-iCBT) DEVICE

The Depression Auxiliary Intervention Treatment Software (WL-iCBT) is a mobile application for smartphones that delivers cognitive behavioral therapy (CBT) and cognitive bias modification (CBM) through structured interactive multimedia methods, including animations, videos, audio, and interactive exercises.

Also known as: WL-iCBT Mobile Application, Wanglinuanyang, WanderLab Nuanyang

Depression Auxiliary Intervention Treatment Software (WL-iCBT)

Placebo Control Software (WL-iHE) DEVICE

The placebo control software (WL-iHE) is a mobile application that mimics the appearance and usage pattern of the active intervention software but lacks the therapeutic cognitive behavioral therapy components. The software has a similar user interface and time requirements, with participants using it once daily for 10-15 minutes, completing a total of 56 sessions over the 8-week treatment period. Unlike the active intervention, the placebo software does not deliver structured cognitive behavioral therapy content or cognitive bias modification training, instead providing general health education information without specific depression treatment techniques.

Also known as: WL-iHE Mobile Application, Health Education Placebo Software for Depression

Placebo Control Software (WL-iHE)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Voluntary participation in the trial with signed informed consent
• Age 18-60 years (inclusive), any gender
• Clinical diagnosis of Major Depressive Disorder (MDD) according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria, confirmed by the Mini-International Neuropsychiatric Interview (M.I.N.I.7.0.2), with either single episode or recurrent episodes without psychotic features
• Montgomery-Asberg Depression Rating Scale (MADRS) score ≥18 and \<30 at screening
• No antidepressant medication within 2 weeks prior to screening (6 weeks for fluoxetine), and assessed by the investigator as able to maintain without antidepressant medication during the trial period
• Education level of primary school or above, able to understand the content of assessment scales, and proficient in using smartphones

You may not qualify if:

• Current clinical diagnosis meeting DSM-5 criteria for psychiatric disorders other than Major Depressive Disorder (confirmed by M.I.N.I.7.0.2)
• Treatment-resistant depression (defined as patients who failed to respond to adequate doses and duration (at least 4 weeks at maximum recommended dose) of 2 or more antidepressants with different chemical structures)
• History of alcohol and drug dependence
• Pregnant or lactating women, or men or women planning pregnancy during the clinical trial period
• Obvious suicidal attempt or behavior, with a score ≥4 on item 10 "Suicidal Thoughts" of the MADRS scale
• Patients who have received other antidepressant treatments within 3 months prior to enrollment, including Chinese herbal medicine, modified electroconvulsive therapy, transcranial magnetic stimulation, biofeedback therapy, light therapy, acupuncture, and other physical or systematic psychological treatments
• Patients who explicitly express unwillingness to participate in psychological therapy or believe psychological therapy is ineffective
• Patients who have participated in or are currently participating in drug clinical trials within 3 months prior to screening, or in other device clinical trials within 1 month prior to screening
• Other conditions deemed unsuitable for enrollment by the investigator

Sponsors & Collaborators

• Adai Technology (Beijing) Co., Ltd.: lead

Study Sites (11)

Shenzhen Kangning Hospital

Shenzhen, Guangdong, China

Location

The Fifth Affiliated Hospital of Sun Yat-sen University

Zhuhai, Guangdong, China

Location

The First Hospital of Hebei Medical University

Shijiazhuang, Hebei, China

Location

Zhumadian Second People's Hospital

Zhumadian, Henan, China

Location

The Second Xiangya Hospital of Central South University

Changsha, Hunan, China

Location

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shannxi, China

Location

Chengdu Fourth People's Hospital (Chengdu Mental Health Center)

Chengdu, Sichuan, China

Location

The First Affiliated Hospital of Kunming Medical University

Kunming, Yunan, China

Location

Zhejiang Provincial Tongde Hospital

Hangzhou, Zhejiang, China

Location

Ningbo Kangning Hospital

Ningbo, Zhejiang, China

Location

Quzhou Third Hospital

Quzhou, Zhejiang, China

Location

MeSH Terms

Conditions

Depression

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2022
• First Posted: September 26, 2022
• Study Start: April 21, 2023
• Primary Completion: March 15, 2024
• Study Completion: October 25, 2024
• Last Updated: September 24, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (11)