Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics

NCT05877885 | Recruiting DMC

• 2 other identifiers: 22-09025304K23MH129882
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this randomized controlled trial is to evaluate the potential of a customized digital cognitive training intervention to target aspects of brain function in apathy of late-life depression and reduce symptoms of apathy and related cognitive and behavioral deficits. The investigators hypothesize that 4 weeks of a customized digital cognitive training program will lead to changes in brain connectivity, apathy severity, and cognitive control performance.

Conditions

Major Depressive Disorder; Apathy

Outcome Measures

Primary Outcomes (1)

• Change in Resting State Functional Connectivity among the Salience, Executive Control, and Reward Networks

  Calculated from resting state fMRI scan. Validation of target engagement.

  Baseline and Post-treatment (Week 4)

Secondary Outcomes (2)

• Change in Apathy Evaluation Scale (AES) score

  Baseline, Mid-treatment (Week 2), and Post-treatment (Week 4)

• Change in Stroop Interference score

  Baseline, Mid-treatment (Week 2), and Post-treatment (Week 4)

Study Arms (2)

Targeted Cognitive Training Intervention

EXPERIMENTAL

Behavioral: Targeted Cognitive Training Intervention

General Cognitive Training Intervention

ACTIVE COMPARATOR

Behavioral: General Cognitive Training Intervention

Interventions

Targeted Cognitive Training Intervention BEHAVIORAL

In this intervention, participants will complete 25-30 minutes of cognitive training per day, 5 days/week (but up to 7 days/week) for 4 weeks. The training protocol will be delivered via the Posit Science Platform, and includes tasks that emphasize training of sustained attention, salience detection, and dimensions of cognitive control. During the 4 week intervention, participants will have weekly 10-20 minute visits with a Care Manager to provide clinical monitoring of symptoms and structured support to participants.

Targeted Cognitive Training Intervention

General Cognitive Training Intervention BEHAVIORAL

In this intervention, participants will complete 25-30 minutes of cognitive activities per day, 5 days/week (but up to 7 days/week) for 4 weeks. The training protocol will be delivered via the Posit Science Platform. The intervention protocol will include computerized cognitive activities designed to provide general cognitive stimulation. During the 4 week intervention, participants will have weekly 10-20 minute visits with a Care Manager to provide clinical monitoring of symptoms and structured support to participants.

General Cognitive Training Intervention

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 60+ years
• Diagnosis of unipolar major depressive disorder without psychotic features, as assessed by the Mini International Neuropsychiatric Interview
• Montgomery-Åsberg Depression Rating Scale (MADRS) score \> or = 16.
• Clinically significant apathy, determined by the Clinician-rated Apathy Evaluation Scale (C-AES \> or = to 37)
• Off antidepressants or on a stable dose of an antidepressant for 8 weeks and do not intend to change the dose in the next 5 weeks.
• On a stable dose of other psychotropic medications, deemed by the investigator to be associated with brain networks of interest, for at least 8 weeks.
• Capacity to provide written consent for research assessment and treatment
• Ability to follow written and verbal instructions (English) as assessed by the PI and/or study staff.
• Total score of \> 29 on the Telephone Interview for Cognitive Status (TICS)
• Eligible to undergo MRI
• Access to a computer or tablet with Wifi capabilities
• Able to comply with all testing and study requirements and willingness to participate in the full study duration.

You may not qualify if:

• History or presence of psychiatric diagnoses other than major depressive disorder without psychotic features, persistent depressive disorder, generalized anxiety disorder, social anxiety disorder, or specific phobia
• Use of cholinesterase inhibitors or psychoactive drugs other than antidepressants or benzodiazepines, including antipsychotics, that in the opinion of the Investigator may confound study data/assessments.
• Presence or history of significant neurologic or neurodegenerative disorder (e.g., Alzheimer's disease and other dementias, amnestic Mild Cognitive Impairment, history of stroke, Multiple Sclerosis, Parkinson's disease, epilepsy).
• Any other acute medical condition (e.g., cardiac, renal, or respiratory failure; severe chronic obstructive pulmonary disease; metastatic cancer; or debilitated states or less common medical illnesses) that may influence brain systems of interest or interfere with participation or interpretation of the study results.
• Participant is currently considered at risk for attempting suicide by the Investigator, has made a suicide attempt within the past year, or is currently demonstrating active suicidal ideation or self-injurious behavior.
• Electroconvulsive therapy within the past 12 months
• Recent history (within 6 months prior to screening/baseline) of Substance Use Disorder.
• Claustrophobia
• Color Blindness
• Sensory or physical impairment that would preclude cognitive testing or participation in the intervention (e.g., upper limb paralysis) as reported by the participant or observed by the Investigator.
• Travelling consecutively for 2+ weeks during the study period to a location that will preclude timely collection of post-treatment MRI data.
• Contraindications to MRI scanning including cardiac pacemaker, heart valve replacement, vascular stent, cochlear implant, any other metallic biomedical implant contraindicating to MRI.

Sponsors & Collaborators

• AdventHealth: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

AdventHealth Neuroscience Institute

Orlando, Florida, 32804, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major; Lethargy

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Lauren Oberlin, PhD

  AdventHealth

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lauren Oberlin, PhD

CONTACT

(860) 690-8441; lauren.oberlin@adventhealth.com

Study Design

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

Study Record Dates

• First Submitted: May 17, 2023
• First Posted: May 26, 2023
• Study Start: September 19, 2025
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: October 22, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, ANALYTIC CODE
• Time Frame: Beginning 3 months following publication of primary outcomes, ending 5 years following publication of primary outcomes.
• Access Criteria: Data will be made available to researchers who provide a methodologically sound proposal, to achieve the aims in the approved proposal. Proposals should be directed to the study PI, Lauren Oberlin, at lauren.oberlin@adventhealth.com

Locations

US (1)