Fitness for Brain Optimization for Late-Life Depression (FIT BOLD)
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ClinicalTrials.gov Identifier: NCT04670510 |
Recruitment Status :
Recruiting
First Posted : December 17, 2020
Last Update Posted : August 18, 2023
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Tracking Information | |||||||||
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First Submitted Date ICMJE | December 10, 2020 | ||||||||
First Posted Date ICMJE | December 17, 2020 | ||||||||
Last Update Posted Date | August 18, 2023 | ||||||||
Actual Study Start Date ICMJE | August 4, 2021 | ||||||||
Estimated Primary Completion Date | March 2026 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Same as current | ||||||||
Change History | |||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | Fitness for Brain Optimization for Late-Life Depression | ||||||||
Official Title ICMJE | Aerobic Exercise for Optimizing Cognitive and Brain Health in Remitted Late-Life Depression | ||||||||
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. | ||||||||
Detailed Description | Significance: The population of adults aged >65 years in United States is expected to nearly double between 2012 and 2050, with a projected estimate of 83.7 million adults aged >65 years by 2050. The prevalence of depressive symptoms among older adults ranges 15 - 27% in the community and up to 37% in primary care settings. Though subclinical depressive symptoms are more prevalent than Major Depression (MDD) among older adults (MDD: 5.5% prevalence), rates of MDD in older people have been rising over the past two decades. Late-life depression (LLD) results in enormous economic, public health, and caregiver burden. This high economic cost consists of both direct and indirect costs (e.g., increased use of medical resources, need for unpaid family caregiving). Further, LLD exacerbates chronic medical illness burden and confers the greatest risk for mortality across all mental health conditions in aging. LLD also increases disability risk, with one report estimating 79% of LLD having functional limitations. Importantly, those with LLD are at a twofold increased risk for dementia relative to the general aging population, which has catastrophic implications for the long-term economic and public health burden of LLD. Background: Older adults with LLD are particularly predisposed to accelerated rates of cognitive decline and progression to dementia. While nearly half of those with LLD have significant cognitive impairment, cognitive deficits are inadequately addressed using conventional antidepressant treatments. Exercise has emerged as the leading non-pharmacological approach to improve cognition and reduce dementia risk in aging. AE interventions in older adults, over as short as 6-months, have been shown to improve performance in cognitive functions (i.e., executive function) and brain regions and networks (i.e., PFC, HC, DMN) that are most sensitive to the neurotoxic effects of LLD. However, our knowledge of AE-related cognitive and brain changes in aging are primarily drawn from AE trials conducted in populations at low risk for dementia. Though an emerging literature supports the benefits of AE for cognitive and brain health in those with MCI, these studies systemically exclude psychiatric populations. By excluding those with LLD, existing studies are overlooking a subsample of older adults at ultra-high risk for dementia for whom the cognitive and neural benefits of AE training may be particularly consequential. This necessitates a better understanding of the potential of AE training to target systemic brain features and cognition in those who have had LLD. Impact: This study will probe whether AE -related systemic brain changes may be mechanistic targets for improving cognition in those with rLLD. It cannot be assumed that AE effects on brain health will be consistent across populations with varying levels of brain-related abnormalities. This study allows for an initial exploration of the extent to which AE effects on cognitive and brain health in those with rLLD are similar to and distinct from AE effects on cognitive and brain health in older adults who 1) are cognitively normal or 2) do not have a history of LLD, for whom the majority of the AE brain health and cognition literature is based. Study Aims: Aim 1. Examine AE effects on structural and functional neuroimaging markers of brain health in rLLD. H1a. AE relative to SE will result in greater preservation of gray matter integrity in areas shown to be abnormal in LLD (HC and PFC) but not in the occipital cortex or thalamus. H1b. AE relative to SE will result in enhanced functional connectivity within the DMN and cross-network connectivity between the DMN and ECN. H1a. Separate ANCOVA models will be used to examine intervention group differences in change in HC and thalamus volume (mm3) and cortical thickness of PFC regions (i.e., dorsolateral PFC, medial orbitofrontal cortex, and ACC) and the occipital cortex, from baseline to 6-months, all of which will be estimated using semiautomated segmentation methods. H1b. Primary analysis of resting state functional magnetic resonance (fMRI) data will involve ANCOVAs to examine group differences in change in within-network DMN connectivity and cross-network DMN-ECN connectivity using summary network connectivity measures. Linear mixed models testing group x time interaction effect for PCC-whole brain voxel-wise connectivity maps will be used in secondary analyses. Aim 2. Examine AE effects on cognitive functioning in rLLD. H2. AE relative to SE will improve cognitive performance, showing the greatest effect for executive functioning. Primary analyses will use ANCOVA models to examine group differences in change in performance for each cognitive domain from baseline to 6-months. Secondary analyses will involve random slopes and random intercept models for repeated longitudinal data to examine group differences in trajectory of change in performance for each cognitive domain over 6-months across three timepoints (baseline, 3-months, 6-months). Exploratory analyses will also involve a comparison of group differences in trajectory of change in objective cognitive performance relative to subjective reports of cognitive functioning. (Exploratory) Aim 3. Explore the extent to which AE-related structural and functional brain changes are associated with AE-related cognitive changes in those with rLLD. H3. AE-related changes in HC and/or PFC integrity and/or DMN connectivity will be associated with AE-related cognitive changes. H3. Pearson's correlations will be used to examine the association between change in brain outcomes showing an effect of AE training and change in performance for cognitive domains showing an effect of AE training. |
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Study Type ICMJE | Interventional | ||||||||
Study Phase ICMJE | Not Applicable | ||||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Investigator, Outcomes Assessor) Primary Purpose: Basic Science |
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Condition ICMJE | Depression in Old Age | ||||||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE |
50 | ||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||
Estimated Study Completion Date ICMJE | June 2026 | ||||||||
Estimated Primary Completion Date | March 2026 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 60 Years and older (Adult, Older Adult) | ||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | United States | ||||||||
Removed Location Countries | |||||||||
Administrative Information | |||||||||
NCT Number ICMJE | NCT04670510 | ||||||||
Other Study ID Numbers ICMJE | STUDY20080088 K23MH125074 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | No | ||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | Swathi Gujral, University of Pittsburgh | ||||||||
Original Responsible Party | Same as current | ||||||||
Current Study Sponsor ICMJE | University of Pittsburgh | ||||||||
Original Study Sponsor ICMJE | Same as current | ||||||||
Collaborators ICMJE | National Institute of Mental Health (NIMH) | ||||||||
Investigators ICMJE |
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PRS Account | University of Pittsburgh | ||||||||
Verification Date | August 2023 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |