Clinical Trials Logo

Clinical Trial Summary

This randomized control trial will examine whether a 12 month monitored exercise intervention improves brain health in cognitively normal older adults. This trial will also address several important unanswered questions: (1) Are the recommended public health guidelines of 150 minutes/week of exercise sufficient for improving cognitive performance? (2) Does exercise influence brain structure and/or function? (3) Is there a dose-response effect of exercise on the above variables such that greater amounts of exercise brings about greater benefits in cognitive and brain health? (4) What are the mechanisms by which exercise influences brain health? and (5) What factors attenuate or magnify the effects of exercise on brain and cognitive health and contribute to the individual variability in intervention outcomes?

Clinical Trial Description

The investigators are conducting a 12-month, multi-site, randomized dose-response exercise trial (i.e., brisk walking) in 639 cognitively normal adults between 65-80 years of age. Participants will be randomized to a (a) moderate intensity aerobic exercise condition at the public health recommended dose of 150 minutes/week (N=213), (b) a moderate intensity exercise condition at 225 minutes/week (N=213), or (c) a light intensity stretching-and-toning control condition for 150 minutes per week (N=213). Participants will meet 3 days/week for site-based exercise and do home-based activity on two more days of the week for 12 months. A comprehensive state-of-the-science battery of cognitive, MRI, amyloid imaging, physiological biomarkers, cardiorespiratory fitness, physical function, and quality of life measures will be assessed at baseline and after completion of the intervention. Due to Covid-19 pandemic, the exercise intervention was moved to fully home based during the months of March 2020 through August 2020. During this time, study participants were mailed wrist based heart rate monitors to track intensity. Exercise videos were developed and released to study participants to enhance adherence to the prescribed volume of exercise. Study participants were contacted weekly to obtain weekly exercise volume, mode and intensity. From August 2020 to end of the trial, participants will have flexibility to complete randomized goal of exercise. The study recommends three supervised sessions per week but will work with study participants who feel unsafe exercising in one of the study locations. The outcome measures to be collected during March 2020 and July 2020 were delayed in those subjects had original intervention end date during this time. For these study participants, many signed a study consent extension and continued the intervention until study sites were allowed to re-open after careful planning and approved mitigation plans at each respective university. Once approved to re-open, participants were scheduled for their post assessment outcome collection. Specific Aims include: 1. Cognitive Enhancement: Using a comprehensive neuropsychological battery and the NIH Toolbox, the investigators will test (a) whether a 12-month moderate intensity exercise intervention improves cognitive performance in older adults and (b) whether the improvements occur in a dose-dependent manner. Hypothesis: PA will enhance cognitive performance non-uniformly with the greatest effects occurring for executive and declarative memory functions. The investigators also predict that these improvements will follow a dose-dependent trajectory with 225 minutes/week of PA demonstrating greater improvements than 150 minutes/week of PA. 2. Brain Augmentation: The investigators will test (a) whether a 12-month PA intervention augments MRI markers of brain health and (b) whether changes happen in a dose-dependent manner. Hypothesis: PA will most profoundly influence the volume, microstructural white matter integrity, cerebral blood flow, and connectivity of regions supporting declarative memory (e.g., hippocampus) and executive function (e.g., prefrontal cortex; PFC). Further, the investigators predict that 225 minutes/week will result in greater effects than 150 minutes/week. The investigators predict that these changes in brain outcomes will mediate the cognitive improvements in Aim 1. 3. Biomediators: The investigators will test the hypothesis that cardiometabolic, inflammatory, and neurotrophic changes mediate improvements in brain and cognition. Hypothesis: (1) decreases in pro-inflammatory cytokines, (2) decreases in central adiposity, arterial stiffness, and insulin resistance, and (3) increases in brain-derived neurotrophic factor (BDNF) levels will statistically mediate changes in cognitive performance (Aim 1) and brain health (Aim 2), and that the strength of this mediating relationship might vary as a function of certain apriori moderating variables of interest 4. Moderators: To examine subgroups (i.e., individual differences) that attenuate or magnify the effect of the intervention on cognitive, brain, and physiological systems to better understand the factors that predict 'responders' versus 'non-responders' to the intervention. The investigators will examine three categories of variables: (1) demographic (e.g., age) (2) genetic (e.g., APOE), and (3) baseline Aβ burden. Hypothesis: The favorable effects of PA on brain and cognition will be greatest for older individuals with greater Aβ burden, and in those with a genetic susceptibility for accelerated cognitive decline. 5. Amyloid Diminution: We will test (a) assess Amyloid deposition changes in response to physical activity and (b) whether changes occur in a dose-dependent manner and (c) examine baseline Amyloid as a moderator of intervention effects and (d) examine changes in Amyloid as a mediator of changes in brain and cognition. Hypothesis: We predict that Aβ burden will be attenuated over the course of the intervention for the aerobic exercise groups compared to control group. Further, we predict that 225 minutes/week of aerobic exercise will result in a greater effect on Aβ than 150 minutes/week 6. Exploratory Aims: The investigators will explore (a) whether baseline brain health metrics predict adherence and compliance to 12-months of PA, and (b) the utility of multi-modal brain imaging analytical approaches to more comprehensively understand the effects of PA on the aging brain. ;

Study Design

Related Conditions & MeSH terms

NCT number NCT02875301
Study type Interventional
Source University of Pittsburgh
Status Active, not recruiting
Phase Phase 3
Start date September 6, 2017
Completion date December 31, 2023

See also
  Status Clinical Trial Phase
Recruiting NCT04632485 - Early Detection of Vascular Dysfunction Using Biomarkers From Lagrangian Carotid Strain Imaging
Terminated NCT04556032 - Effects of Ergothioneine on Cognition, Mood, and Sleep in Healthy Adult Men and Women N/A
Completed NCT04998695 - Health Effects of Consuming Olive Pomace Oil N/A
Completed NCT04107441 - AX-8 Drug Safety, Tolerability and Plasma Levels in Healthy Subjects Phase 1
Completed NCT04065295 - A Study to Test How Well Healthy Men Tolerate Different Doses of BI 1356225 Phase 1
Completed NCT01442831 - Evaluate the Absorption, Metabolism, And Excretion Of Orally Administered [14C] TR 701 In Healthy Adult Male Subjects Phase 1
Recruiting NCT04967157 - Cognitive Effects of Citicoline on Attention in Healthy Men and Women N/A
Completed NCT05030857 - Drug-drug Interaction and Food-effect Study With GLPG4716 and Midazolam in Healthy Subjects Phase 1
Recruiting NCT04714294 - Evaluate the Safety, Tolerability and Pharmacokinetics Characteristics of HPP737 in Healthy Volunteers Phase 1
Recruiting NCT04494269 - A Study to Evaluate Pharmacokinetics and Safety of Tegoprazan in Subjects With Hepatic Impairment and Healthy Controls Phase 1
Completed NCT04539756 - Writing Activities and Emotions N/A
Recruiting NCT04098510 - Concentration of MitoQ in Human Skeletal Muscle N/A
Completed NCT03308110 - Bioavailability and Food Effect Study of Two Formulations of PF-06650833 Phase 1
Completed NCT04052711 - A Randomized, Controlled Study to Evaluate the Sensitizing Potential of FMX-101 in Healthy Volunteers Using a Repeat Insult Patch Test Design Phase 1
Terminated NCT00001844 - Study of New Magnetic Resonance Methods
Completed NCT04451811 - A PK Dose Proportionality Study of OPL-002 in Healthy Volunteers Phase 1
Completed NCT04319926 - Adhesion Performance Study of Lidocaine Topical System 1.8% Compared to Generic Lidocaine Patch 5% in Healthy, Adult, Human Subjects Phase 1
Completed NCT03160261 - Effect of Exenatide on Cortisol Secretion Phase 4
Completed NCT05005065 - Evaluation of the Pharmacokinetics/Pharmacodynamics and Safety/Tolerability of IN-C005 and IN-A001 in Healthy Caucasians Phase 1
Completed NCT03662100 - A Study of Two Formulations of LY3074828 in Healthy Participants Phase 1