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

Not Applicable

Not yet recruiting

• Conditions: Apathy; Major Depressive Disorder
• Interventions: Behavioral: General Cognitive Training Intervention; Behavioral: Targeted Cognitive Training Intervention

• Registration Number: NCT05877885
• Lead Sponsor: AdventHealth

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-05-17
• Study First Submitted QC: 2023-05-17
• Study First Posted: 2023-05-26
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-11
• Last Update Posted: 2025-02-12
• Study Start: 2025-03-15
• Primary Completion: 2028-11-01
• Study Completion: 2028-12-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 84

Inclusion Criteria

1. Age 60+ years
2. Diagnosis of unipolar major depressive disorder without psychotic features, as assessed by the Mini International Neuropsychiatric Interview
3. Montgomery-Åsberg Depression Rating Scale (MADRS) score > or = 16.
4. Clinically significant apathy, determined by the Clinician-rated Apathy Evaluation Scale (C-AES > or = to 37)
5. 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.
6. 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.
7. Capacity to provide written consent for research assessment and treatment
8. Ability to follow written and verbal instructions (English) as assessed by the PI and/or study staff.
9. Total score of > 29 on the Telephone Interview for Cognitive Status (TICS)
10. Eligible to undergo MRI
11. Access to a computer or tablet with Wifi capabilities
12. Able to comply with all testing and study requirements and willingness to participate in the full study duration.

Exclusion Criteria

1. 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
2. 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.
3. 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).
4. 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.
5. 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.
6. Electroconvulsive therapy within the past 12 months
7. Recent history (within 6 months prior to screening/baseline) of Substance Use Disorder.
8. Participant is currently enrolled in ongoing concurrent cognitive rehabilitation (note that if a subject is enrolled in psychotherapy, this will not be grounds for exclusion)
9. Claustrophobia
10. Color Blindness
11. 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.
12. Travelling consecutively for 2+ weeks during the study period to a location that will preclude timely collection of post-treatment MRI data.
13. Contraindications to MRI scanning including cardiac pacemaker, heart valve replacement, vascular stent, cochlear implant, any other metallic biomedical implant contraindicating to MRI.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
General Cognitive Training Intervention	General Cognitive Training Intervention	-
Targeted Cognitive Training Intervention	Targeted Cognitive Training Intervention	-

Primary Outcome Measures

Name	Time	Method
Change in Resting State Functional Connectivity among the Salience, Executive Control, and Reward Networks	Baseline and Post-treatment (Week 4)	Calculated from resting state fMRI scan. Validation of target engagement.

Secondary Outcome Measures

Name	Time	Method
Change in Apathy Evaluation Scale (AES) score	Baseline, Mid-treatment (Week 2), and Post-treatment (Week 4)	The 18-item clinician-rated version of the Apathy Evaluation Scale (AES) will be used to measure apathy severity. Scores range from 18 (no apathy) to 72 (severe apathy).
Change in Stroop Interference score	Baseline, Mid-treatment (Week 2), and Post-treatment (Week 4)	Stroop interference will be calculated from the computerized Stroop Task to measure cognitive control.

Trial Locations

Locations (2)

AdventHealth Neuroscience Institute; 🇺🇸 Orlando, Florida, United States

Lauren Elizabeth Oberlin; 🇺🇸 Orlando, Florida, United States