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

NCT ID: NCT05554289

Last Updated: 2025-09-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 315 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-21
• Study Completion Date: 2024-10-25

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.

Detailed Description

This investigation is a combined study that consists of an 8-week randomized controlled trial and a 26-week extended observational follow-up. It adopts a superiority design. Participants are stratified and randomly assigned in a 1:1 ratio. They are divided into two groups. One group is the active intervention group, which uses the WL-iCBT software. This software provides structured cognitive behavioral therapy (CBT) modules and attention bias modification training. The other group is the control group, which uses a placebo software. The placebo software has a matched interface but contains non-therapeutic content.

The intervention protocol requires participants to have 56 sessions over 8 weeks. Each day, they have one session, and each session lasts for 10-15 minutes. To meet the requirements, participants need to complete at least 42 sessions. The blinding of the trial is maintained through identical device interfaces for both groups.

The assessment timeline is divided into two phases. During the core treatment phase, which lasts from Week 0 to Week 8, assessments are carried out at baseline, Week 4 (±7 days), and Week 8 (±7 days). In the 26-week extended observation phase quarterly follow-ups are conducted for relapse monitoring and long-term safety assessment.

There are key assessments in this study. The primary endpoint is the change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to Week 8. The secondary endpoints include the MADRS response rate, which is defined as a ≥50% improvement; the MADRS remission rate, which means a score ≤10; changes in the Hamilton Anxiety Rating Scale (HAMA); functional improvement as measured by the Sheehan Disability Scale (SDS); clinician assessments using the Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I); and scores on the Perceived Deficiencies of Depression Questionnaire (PDQ-D) for cognitive function.

Safety monitoring is an important part of the study. All adverse events (AE) and serious adverse events (SAE) are recorded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 27.0. Device-related adverse events are also assessed. Thyroid function is monitored through measuring thyroid-stimulating hormone (TSH) levels, and suicide risk is tracked via Item 10 of the MADRS.

The study population has specific characteristics. Participants are diagnosed with major depressive disorder (MDD) according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, which are confirmed by the Mini-International Neuropsychiatric Interview (MINI) 7.0.2. Those with treatment-resistant depression, those using psychotropic medications, and those with comorbid psychiatric disorders are excluded from the study.

The statistical plan of the study involves a sample size of 315 participants, with 155 in each group, taking into account a 20% dropout rate. There are three analysis sets: the Full Analysis Set (FAS), the Per Protocol Set (PPS), and the Safety Set (SS). The primary analysis uses a mixed-model for repeated measures (MMRM) to analyze the change in MADRS scores, with a superiority margin greater than 0. This integrated design enables a comprehensive evaluation of both the acute therapeutic effects and the sustained outcomes while maintaining the integrity of the trial throughout the extended observation period.

Conditions

Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Depression Auxiliary Intervention Treatment Software (WL-iCBT)

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.

Group Type: EXPERIMENTAL

Depression Auxiliary Intervention Treatment Software (WL-iCBT)

Intervention Type: 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.

Placebo Control Software (WL-iHE)

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.

Group Type: PLACEBO_COMPARATOR

Placebo Control Software (WL-iHE)

Intervention Type: 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.

Interventions

Depression Auxiliary Intervention Treatment Software (WL-iCBT)

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.

Intervention Type: DEVICE

Placebo Control Software (WL-iHE)

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.

Intervention Type: DEVICE

Other Intervention Names

WL-iCBT Mobile Application; Wanglinuanyang; WanderLab Nuanyang; WL-iHE Mobile Application; Health Education Placebo Software for Depression

Eligibility Criteria

Inclusion Criteria

1. Voluntary participation in the trial with signed informed consent

2. Age 18-60 years (inclusive), any gender

3. 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

4. Montgomery-Asberg Depression Rating Scale (MADRS) score ≥18 and <30 at screening

5. 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

6. Education level of primary school or above, able to understand the content of assessment scales, and proficient in using smartphones

Exclusion Criteria

1. Current clinical diagnosis meeting DSM-5 criteria for psychiatric disorders other than Major Depressive Disorder (confirmed by M.I.N.I.7.0.2)

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)

3. History of alcohol and drug dependence

4. Pregnant or lactating women, or men or women planning pregnancy during the clinical trial period

6. Obvious suicidal attempt or behavior, with a score ≥4 on item 10 "Suicidal Thoughts" of the MADRS scale

7. 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

8. Patients who explicitly express unwillingness to participate in psychological therapy or believe psychological therapy is ineffective

9. 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

10. Other conditions deemed unsuitable for enrollment by the investigator

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Adai Technology (Beijing) Co., Ltd.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Shenzhen Kangning Hospital

Shenzhen, Guangdong, China

The Fifth Affiliated Hospital of Sun Yat-sen University

Zhuhai, Guangdong, China

The First Hospital of Hebei Medical University

Shijiazhuang, Hebei, China

Zhumadian Second People's Hospital

Zhumadian, Henan, China

The Second Xiangya Hospital of Central South University

Changsha, Hunan, China

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shannxi, China

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

Chengdu, Sichuan, China

The First Affiliated Hospital of Kunming Medical University

Kunming, Yunan, China

Zhejiang Provincial Tongde Hospital

Hangzhou, Zhejiang, China

Ningbo Kangning Hospital

Ningbo, Zhejiang, China

Quzhou Third Hospital

Quzhou, Zhejiang, China

Countries

China

Other Identifiers

ICBT2021

Identifier Type: -

Identifier Source: org_study_id