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

Major Depressive Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05877885
• Other study ID #: 22-09025304
• Secondary ID: K23MH129882
• Status: Not yet recruiting
• Phase: N/A
• Start date: August 1, 2024
• Est. completion date: December 2028

Study information

• Verified date: May 2024
• Source: Weill Medical College of Cornell University
• Contact: Lauren Oberlin, PhD
• Phone: (646) 289-5204
• Email: leo4001[@]med.cornell.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 84
• Est. completion date: December 2028
• Est. primary completion date: November 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Apathy
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

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.
• 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.

Locations

Country	Name	City	State
United States	Lauren Elizabeth Oberlin	New York	New York
United States	Weill Cornell Medicine Institute of Geriatric Psychiatry	White Plains	New York

Sponsors (2)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)