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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Major Depressive Disorder; Apathy
• Intervention / Treatment: Behavioral: Targeted Cognitive Training Intervention; Behavioral: General Cognitive Training Intervention

• Study Type: Interventional
• Enrollment (Estimated): 84
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lauren Oberlin, PhD; Phone Number: 707 (646) 289-5204; Email: leo4001@med.cornell.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Lauren Elizabeth Oberlin
      • Contact: Lauren E Oberlin, PhD; Phone Number: 707 646-289-5204; Email: leo4001@med.cornell.edu
      • Principal Investigator: Lauren Oberlin, PhD
    • White Plains, New York, United States, 10605
      • Weill Cornell Medicine Institute of Geriatric Psychiatry
      • Contact: Lauren E Oberlin, PhD; Phone Number: 707 646-289-5204; Email: leo4001@med.cornell.edu
      • Principal Investigator: Lauren Oberlin, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 60+ years
2. Diagnosis of unipolar major depressive disorder without psychotic features, as assessed by the Structured Clinical Interview for DSM-5 (SCID)
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. DRS total score > 129 or DRS scaled score of 5 based on age and education-adjusted normative data49
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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Targeted Cognitive Training Intervention	Behavioral: Targeted Cognitive Training Intervention; 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.
Active Comparator: General Cognitive Training Intervention	Behavioral: General Cognitive Training Intervention; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Apathy Evaluation Scale (AES) score	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).	Baseline, Mid-treatment (Week 2), and Post-treatment (Week 4)
Change in Stroop Interference score	Stroop interference will be calculated from the computerized Stroop Task to measure cognitive control.	Baseline, Mid-treatment (Week 2), and Post-treatment (Week 4)

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Lauren Oberlin, PhD, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: May 17, 2023
• First Submitted That Met QC Criteria: May 17, 2023
• First Posted (Actual): May 26, 2023

Study Record Updates

• Last Update Posted (Actual): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: 22-09025304; K23MH129882 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data that will be shared includes all of the individual participant data collected during the trial, after deidentification.
• IPD Sharing Time Frame: Beginning 3 months following publication of primary outcomes, ending 5 years following publication of primary outcomes.
• IPD Sharing 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 leo4001@med.cornell.edu.
• 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