Fitness for Brain Optimization for Late-Life Depression

NCT04670510 | Completed

• 2 other identifiers: STUDY20080088K23MH125074
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

Cognitive impairment and brain abnormalities are common and persist after depression remission in those with Late Life Depression (LLD), compounding dementia risk in both individuals with acute and remitted LLD (rLLD). In this study, investigators will examine systemic neural and cognitive benefits of aerobic exercise training in older adults with remitted LLD. This will generate preliminary data regarding neural targets of aerobic exercise training that may translate to cognitive benefits in those with rLLD, a population who remains at high risk for dementia despite successful treatment of depression.

Conditions

Depression in Old Age

Keywords

Depression; Exercise; Late-Life; Cognitive Impairment; Brain Health

Outcome Measures

Primary Outcomes (5)

• Change from baseline in Cardiovascular Fitness at 6 months

  Cardiorespiratory fitness will be measured via a cardiopulmonary exercise test (CPET) indicated by maximal VO2 on a motorized treadmill. while measuring oxygen utilization via Parvo Medics True one metabolic cart. The test follows a modified Balke protocol in which speed remains constant with the intensity being increased every two minutes via a raise of 2.0% of the incline. The speed was an agreed upon speed between participant and staff (between 2.0 and 4.0 mph). The test will conclude when the participant reaches 85% of age predicted maximal heart rate, rating of perceived exertion (RPE) equal to or greater than 15 for those who have blunted heart rate response due to beta block medication, or volitional termination by participant.

  Baseline and 6-months

• Changes from baseline in Brain Structure and Function at 6 months

  Brain imaging conducted with a 7 Tesla scanner. Of particular interest are changes in hippocampal volume. This measurement is reported in mm\^3, with higher numbers indicating higher levels of gray matter in the hippocampal region. Changes in prefrontal cortical thickness are also of interest, measured in mm. Brain functional network changes of interest are changes in intra- and inter-connectivity of the default-mode and executive control large-scale brain networks.

  Baseline and 6-months

• Changes from baseline in depressive symptoms at 6 months

  Given that all participants will have a recent history of depression, and may have lingering low level symptoms or may even relapse, depressive symptoms will be assessed using the Montgomery Asberg Depression Rating Scale (MADR; score ranges from 0 \[better\] to 60 \[worse\]), a clinician administered measure of depression severity.

  Baseline and 6-months

• Depressive Symptoms

  For the frequent assessment of depressive symptoms during the intervention while minimizing participant and clinician burden, the Patient Health Questionnaire-9 item version (PHQ-9; score ranges from 0 \[better\] to 27 \[worse\]), a self-report questionnaire, will be administered.

  Continuously up to every 6-weeks for 6 months

• Change from baseline in Cognitive Function at 6 months

  Assessed with a comprehensive Neuropsychological Battery. The primary cognitive outcome will be assessed using a composite score (mean) of standardized scores (Z-scores) from the following executive functioning tests from the NIH toolbox: 1) Dimensional Change Card Sort Test (set-shifting), Flanker Inhibitory Control and Attention Test (inhibition), List Sorting Working Memory Test (working memory).

  Baseline and 6-months

Secondary Outcomes (4)

• During-intervention physical activity levels

  Continuously up to every 2 months for 6 months

• Change from baseline in amount of physical activity at 6 months

  Baseline and 6-months

• Changes from baseline in intensity of physical activity at 6 months

  Baseline and 6-months

• Change from baseline in Subjective Cognitive Function at 6 months

  Baseline and 6-months

Study Arms (2)

Aerobic Exercise

EXPERIMENTAL

The Aerobic Exercise (AE) condition will involve 150-minutes of moderate-intensity AE per week for 6-months and will involve a graded decline in supervision. Supervised AE will occur in groups, though each participant's AE prescription will be personalized based on baseline exercise capacity, as assessed by a maximal cardiopulmonary fitness test. Supervised AE sessions will involve the treadmill, elliptical, and/or bike, and routines will be varied to promote adherence. Supervised AE sessions will gradually increase to 50-minutes per session; however, participants will be encouraged to engage in home-based AE sessions according to their own preference of length and frequency in order to achieve 150 minutes of AE per week.

Other: On-site AE; Other: At-home AE

Social Engagement

ACTIVE COMPARATOR

The Social Engagement (SE) condition will be designed to control for the social component of the AE intervention (i.e., supervised on-site sessions with professional staff, frequent phone contact from study staff). A variety of enjoyable group-based activities centered around the dimensions of wellness (spiritual wellness, physical wellness, emotional wellness, etc.) will be scheduled throughout the intervention. This condition will involve once weekly meetings (grand total of \~26 sessions). Some participants will meet in-person and others will meet remotely via zoom (this will vary week to week) to increase flexibility to accommodate participant availability to attend as many sessions as possible.

Other: Social Engagement (SE)

Interventions

On-site AE OTHER

Participants will attend on-site supervised AE sessions 3 times per week for the first 6 weeks, twice weekly for weeks 7-12; once weekly for weeks 13-18. All supervised sessions will start and end with 5-minute warm-up and cool-down and will involve exercise on the treadmill, elliptical, and/or bike. During AE sessions, participants will exercise so that their heart rate is approximately 65% of their peak heart rate and gradually increase the intensity of exercise so that their heart rate is between 70 and 85% of their peak heart rate. All participants will wear heart rate monitors and encouraged to exercise in their target heart rate zone. Supervised AE sessions will gradually increase to 50-minutes per session

Aerobic Exercise

At-home AE OTHER

Participants will increase at-home AE during the 6-month intervention period with weeks 19-26 occurring entirely at-home. As participants transition to home-based exercise, they will be equipped with a polar heart rate monitor and will be instructed to use this to record average heart rate during each exercise session. On a log sheet, they will record both average heart rate during exercise and average subjective rating of perceived exertion (RPE) during each exercise session.

Aerobic Exercise

Social Engagement (SE) OTHER

To control for the social component of the AE intervention participants in the SE group will be invited to attend at total of 25 group meetings over the course of the 6-month study period.

Social Engagement

Eligibility Criteria

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

You may qualify if:

• Men and women 60+ years
• Major Depressive Episode in older adulthood (since age 55)
• Current level of depressive symptoms does not meet criteria for a Major Depressive Episode
• Ambulatory without pain or the assistance of walking devices
• Able to speak and read English
• Exercise level of \<100 minutes per week on average
• Medical clearance by primary care physician (PCP)
• Living in community for duration of the study
• Reliable means of transportation
• No diagnosis of a neurological disease
• Eligible to undergo MRI

You may not qualify if:

• Current diagnosis of a Major Depressive Episode
• Psychosis
• Significant suicide risk (i.e., current, active suicidal ideation with a plan)
• Electroconvulsive therapy within the past 12 months
• Engaging in moderate-intensity exercise \>100 minutes per week on average
• Current treatment for cancer - except non-melanoma skin
• Neurological condition (MS, Parkinson's, Dementia, MCI) or brain injury (Stroke)
• Substance Use disorder in the past 3-months
• Current treatment for congestive heart failure, angina, uncontrolled arrhythmia, deep vein thromboses (DVT) or other cardiovascular event
• Myocardial infarction, coronary artery bypass grafting, angioplasty or other cardiac condition in the past year including uncontrolled hypertension
• Regular use of an assisted walking device
• Presence of metal implants (pacemaker, stents) that would be MR ineligible
• Claustrophobia
• Color Blindness
• Significant visual or hearing impairments that would preclude neuropsychological assessment or communication with study staff via a virtual format (videoteleconference)

Sponsors & Collaborators

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

Study Sites (1)

UPMC Western Psychiatric Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Depression; Motor Activity; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Swathi Gujral, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of the Department of Psychiatry at the University of Pittsburgh, School of Medicine

Study Record Dates

• First Submitted: December 10, 2020
• First Posted: December 17, 2020
• Study Start: August 4, 2021
• Primary Completion: October 22, 2025
• Study Completion: October 22, 2025
• Last Updated: November 28, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

US (1)