Confirmatory Efficacy Trial of Attention Bias Modification for Depression

Confirmatory Efficacy Trial of a Traditional vs. Gamified Attention Bias Modification for Depression

The goal of this clinical trial is to compare the efficacy of two related, but different ABM (Attention Biased Modification) treatments for depression in adults with elevated symptoms of depression. The main aims are:

• Aim 1:examine whether gamified ABM leads to greater change in the primary and secondary outcomes than sham ABM
• Aim 1: establish that gamified ABM is at least as effective as traditional ABM.
• Aim 2: identify moderators of ABM efficacy and mechanisms responsible for its efficacy.
• Aim 3: Identify the durability of ABM on depression symptoms during short-term follow-up

Participants will complete self-report questionnaires, complete eye-tracking tasks, and be clinically assessed through interviews by clinician researchers.

If there is a comparison group: Researchers will compare sham, traditional, and gamified treatment groups to see if they moderate symptoms of depression.

Study Overview

• Status: Not yet recruiting
• Conditions: Depression
• Intervention / Treatment: Behavioral: Gamified Attention Bias Modification; Behavioral: Sham Attention Bias Modification; Behavioral: Traditional Attention Bias Modification

Detailed Description

The overall goal of this project is to conduct a well-powered confirmatory efficacy trial comparing a gamified, attention bias modification (ABM) mobile application and traditional ABM to sham ABM among adults with elevated symptoms of depression. The proposed R01 efficacy trial follows the NIMH intervention development sequence as it builds upon prior NIMH-funded experimental therapeutics work, specifically R21MH092430 "Attention training for Major Depressive Disorder" and R33MH109600 "Development of attention bias modification for depression". This prior work demonstrates that active ABM engages and alters negative attention bias and there is a preliminary efficacy signal that ABM reduces depression. Although traditional ABM is efficacious for the treatment of depression, "gamified" forms of ABM have the potential to be more accessible and engaging than traditional ABM. Pilot work suggests that a gamified ABM can reduce negative affect; however, its effectiveness for depression has not yet been established. Thus, investigators are proposing to conduct a well-powered, confirmatory efficacy trial to determine ABM's potential for the treatment of depression. In Aim 1, the investigators will examine the efficacy of ABM in a large sample of adults (N = 600) with elevated symptoms of depression. The investigators hypothesize that gamified and traditional ABM will lead to significantly greater reductions in self-reported and interviewer-rated depression symptoms than sham ABM. The investigators further hypothesize that traditional ABM will be non-inferior to gamified ABM (treatment superiority between the ABM conditions will also be tested). In Aim 2, the investigators will examine putative moderators and mediators of ABM. Based on ABM research with anxious populations, it is predicted that people with a strong initial attentional bias for sad stimuli will experience greater reductions in depression in response to either gamified or traditional ABM than sham ABM. In terms of mediation, compared to sham ABM, the investigators hypothesize that gamified and traditional ABM will: (1) decrease negative attentional bias measured behaviorally with reliable eye tracking methods; (2) significantly reduce depression; and (3) improve depression symptoms via their influence on negative attentional bias. Selection of the putative mediators is informed by our prior R33 ABM trial, where it was found that gaze bias away from sad stimuli mediated the effect of traditional ABM on depression symptom change. In Aim 3, an exploratory aim, the investigators will estimate the durability of ABM by collecting post-treatment symptom data 1-, 2-, 3-, and 6-months after ABM completion. Symptom change and reliable recovery across a six-month follow-up period will be estimated. Currently, the durability of ABM effects for depression is unknown, as few well-powered ABM studies for depression have obtained follow-up data. This trial would provide the most definitive data to date regarding whether ABM for depression is a promising treatment for depression.

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Christopher G Beevers, PhD; Phone Number: 5124717557; Email: beevers@utexas.edu

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78705
      • Institute for Mental Health Research
      • Contact: Email: beevers@utexas.edu
      • Contact: Christopher G Beevers, PhD; Email: beevers@utexas.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Provided informed consent
• Fluent in English
• Scored 13 or greater on the QIDS-SR at the baseline assessment
• Between the ages of 18 to 70
• Have had no changes in medication and dosage in the past 12 weeks (if currently on antidepressant medication)

Exclusion Criteria:

• Reported suicidal behavior or significant suicidal ideation within the past six months using the Columbia-Suicide Severity Rating Scale (C-SSRS)
• Met criteria for current or past bipolar or psychotic disorders
• Current (i.e., within the past 12 months) substance use disorders of moderate or greater severity on the Mini International Neuropsychiatric Interview (MINI)
• Currently taking opioid analgesics or systemic corticosteroid use as these medications
• Currently receiving psychotherapy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Sham Attention Bias Modification; Sham and traditional ABM interventions will be identical in all respects with one critical exception. For sham ABM, after stimuli offset the target will appear with equal probability (50%) in the location of the neutral or the dysphoric stimulus.	Behavioral: Sham Attention Bias Modification; Sham attention bias modification designed to match the active ABM condition in all respects except for the shifting attention away from negative stimuli in active attention bias modification.
Active Comparator: Traditional Attention Bias Modification; This ABM variant is a web-based program delivered to participants via a computer. It presents pairs of stimuli to the right and left visual fields from two stimulus categories: sad or neutral facial expressions from the Pictures of Facial Affect (POFA) collection and dysphoric or neutral scenes from or from the International Affective Picture System (IAPS) collection.	Behavioral: Traditional Attention Bias Modification; Each ABM trial begins with a central fixation cross for 1500ms, followed by a pair of POFA or IAPS stimuli (see Figure 3). POFA pairs will be presented for 3000ms, while IAPS pairs will be presented for 4500ms (due to the increased image complexity of IAPS images relative to POFA images). Longer stimulus duration times were selected based on evidence that attention biases for sad stimuli are prolonged in depression. Following offset of the images, either a single or double asterisk probe appears in the location of one of the images and will remain until a participant response or 10,000ms. In active ABM, the probe had an 80% probability of appearing in the location of the neutral stimulus. Investigators selected 80% rather than 100% to allow for computing attention bias during training and to facilitate task engagement. At the end of each ABM session, participants are provided feedback regarding their task performance relative to their last five sessions in a visual format.
Experimental: Gamified Attention Bias Modification; This ABM variant will be completed on participants' mobile devices (iOS or Android). During app use, they will be presented with sad-happy stimulus pairs followed by target probes (tracing a path) always appearing at the happy stimulus location.	Behavioral: Gamified Attention Bias Modification; Each trial consists of the fixation stage, facial cue stage, and response stage. At the fixation stage, an image appears (a colorful medallion) for 500 ms. The fixation appears randomly within a fixed rectangular field on the user's smartphone screen, and is always at the midpoint between the two face cues that will appear in the next stage. Next, after the cue disappears, two animated faces appear on the screen, one happy and one sad, with a 1000ms duration. Immediately after they disappear, a target probe (a trail) appears in the location of the happy face cue. The path remains (up to 3 seconds) until participants respond by tracing it starting from the point at which the face cue disappeared. They are instructed to quickly but accurately trace the path with their finger and receive visual and haptic feedback during tracing to indicate they are tracing accurately, followed by the path disappearing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
QIDS (Quick Inventory of Depression Symptoms) SR-16	The Quick Inventory of Depressive Symptoms (QIDS) is a 16-item measure (self-report and clinician-rated versions) for adults with depression with solid psychometric properties and substantial data supporting sensitivity to change. The QIDS assesses the criterion domains used to diagnose a major depressive disorder. The participant must score a minimum of 13 on the QIDS-SR at the baseline assessment to qualify for participation. Total QIDS scores range from 0 to 27, with higher scores reflecting greater severity of depression, and thus, worst outcomes for our study.	Screening, Baseline, Weeks 1-4 (Acute Period), Weeks 12-28 (Follow-Up Period)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sheehan Disability Scale (SDS)	Self-report measure of symptom-related disability. SDS total score ranges from 0 (unimpaired) to 30 (highly impaired). Higher scores mean a worse outcome.	Baseline, Weeks 1-4 (Acute Period), Weeks 12-28 (Follow-Up Period)
Snaith-Hamilton Pleasure Scale (SHAPS)	Self-report measure of anhedonia severity. SHAPS total score ranges from 0 to 14, with higher scores meaning worse outcomes.	Baseline, Weeks 1-4 (Acute Period), Weeks 12-28 (Follow-Up Period)
Hamilton Depression Rating Scale (HAM-D)	Interviewer-rated measure of depression symptom severity. Scoring for this assessment can range from a minimum total score of 0 (least severe) and a maximum score of 52 (most severe). Higher scores mean worse outcomes.	Baseline, Weeks 1-4 (Acute Period), Weeks 12-28 (Follow-Up Period)
Generalized Anxiety Disorder (GAD-7)	Self-report measure of anxiety symptom severity. GAD-7 total score for the seven items ranges from 0 to 21, with higher scores indicating worse outcomes.	Baseline, Weeks 1-4 (Acute Period), Weeks 12-28 (Follow-Up Period)
Perseverative Thinking Questionnaire (PTQ)	A content-independent measures of repetitive negative thinking. PTQ total score for 15 items ranges from 0 to 60, with higher scores indicating worse outcomes.	Baseline, Weeks 1-4 (Acute Period), Weeks 12-28 (Follow-Up Period)

Collaborators and Investigators

• Sponsor: University of Texas at Austin
• Collaborators: Arcade Therapeutics
• Investigators: Principal Investigator: Christopher G Beevers, PhD, UT Austin

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: April 1, 2024
• First Submitted That Met QC Criteria: April 8, 2024
• First Posted (Actual): April 11, 2024

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: attention bias modification; depression treatment; digital mental health treatment
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder
• Other Study ID Numbers: R01GABM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Investigators will share data via the NDAR and code via the Texas Data Repository (https://dataverse.tdl.org/dataverse/mdl). The data is expected to become available at the end of the trial (~ 5 years from now). Qualified researchers, as determined by the NIH's NDAR, will have access to the data. Anyone can access the code. The Study Protocol will be shared via a publication in a protocol journal within the next year.
• IPD Sharing Time Frame: Data is expected to become available at the end of the clinical trial (approximately five years from now) with no end date.
• IPD Sharing Access Criteria: Qualified researchers, as determined by the NIH's NDAR, will have access to the data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

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