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Exercise Effects on Brain Health and Learning From Minutes to Months (EXTEND)

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ClinicalTrials.gov Identifier: NCT03114150
Recruitment Status : Recruiting
First Posted : April 14, 2017
Last Update Posted : December 10, 2019
Sponsor:
Information provided by (Responsible Party):
Michelle W. Voss, University of Iowa

Tracking Information
First Submitted Date  ICMJE March 30, 2017
First Posted Date  ICMJE April 14, 2017
Last Update Posted Date December 10, 2019
Actual Study Start Date  ICMJE May 1, 2018
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 10, 2017)
Change in hippocampal-dependent learning [ Time Frame: Baseline, 24-weeks ]
Learning rate on constructs that have been examined in animal models including context acquisition, episodic associations, and spatial navigation.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 6, 2019)
  • Change in hippocampal-cortical functional connectivity [ Time Frame: Baseline, 30 minutes ]
    The strength of the correlation between the spontaneous functional magnetic resonance imaging (fMRI) signal in the hippocampus and cortical regions in a hippocampal-cortical memory system.
  • Change in hippocampal-cortical functional connectivity [ Time Frame: Baseline, 24-weeks ]
    The strength of the correlation between the spontaneous functional magnetic resonance imaging (fMRI) signal in the hippocampus and cortical regions in a hippocampal-cortical memory system.
  • Change in cardiorespiratory fitness [ Time Frame: Baseline, 24-weeks ]
    Cardiorespiratory fitness will be measured during a maximal exercise test. Oxygen uptake (VO2) will be measured from expired air samples taken at 30 second intervals until a peak VO2, the highest VO2, is attained at the point of test termination due to symptom limitation and/or volitional exhaustion.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 10, 2017)
  • Change in hippocampal-cortical functional connectivity [ Time Frame: Baseline, 30 minutes ]
    The strength of the correlation between the spontaneous functional magnetic resonance imaging (fMRI) signal in the hippocampus and cortical regions in a hippocampal-cortical memory system.
  • Change in hippocampal-cortical functional connectivity [ Time Frame: Baseline, 24-weeks ]
    The strength of the correlation between the spontaneous functional magnetic resonance imaging (fMRI) signal in the hippocampus and cortical regions in a hippocampal-cortical memory system.
  • Change in hippocampal blood flow [ Time Frame: Baseline, 30 minutes ]
    MRI (Arterial Spin Labeling) will be used to measure blood flow of the hippocampus and the hippocampal-cortical memory system.
  • Change in hippocampal blood flow [ Time Frame: Baseline, 24-weeks ]
    MRI (Arterial Spin Labeling) will be used to measure blood flow of the hippocampus and the hippocampal-cortical memory system.
  • Change in structural hippocampal-cortical connectivity [ Time Frame: Baseline, 24-weeks ]
    MRI will be used to assess the structural integrity of pathways in the hippocampal-cortical memory system.
  • Change in relational memory [ Time Frame: Baseline, 24-weeks ]
    Relational memory measure will include tests known to require the hippocampus, including verbal list learning, face-name memory, and spatial reconstruction. The outcome will be examined as a composite measure. The composite measure will be created by z-score normalizing scores for individual tests across all participants, and averaging the z-score normalized scores to create a composite score for each participant.
  • Change in executive function [ Time Frame: Baseline, 24-weeks ]
    Executive function measure will include tests of inhibitory control, updating, and switching. The outcome will be examined as a composite measure. The composite measure will be created by z-score normalizing scores for individual tests across all participants, and averaging the z-score normalized scores to create a composite score for each participant.
  • Change in cardiorespiratory fitness [ Time Frame: Baseline, 24-weeks ]
    Cardiorespiratory fitness will be measured during a maximal exercise test. Oxygen uptake (VO2) will be measured from expired air samples taken at 30 second intervals until a peak VO2, the highest VO2, is attained at the point of test termination due to symptom limitation and/or volitional exhaustion.
  • Change in functional fitness [ Time Frame: Baseline, 24-weeks ]
    Functional fitness for activities of daily living will be measured with the Senior Fitness Test.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Exercise Effects on Brain Health and Learning From Minutes to Months
Official Title  ICMJE Exercise to Improve Hippocampal Connectivity and Learning in Older Adults
Brief Summary Given the accelerating growth of older adults worldwide and the decline in cognitive function with aging, therapeutics that remediate age-related cognitive decline are needed more than ever. The proposed research seeks to better understand and enhance the detection of exercise effects on hippocampal network function and learning and memory, which decline with aging and Alzheimer's. Success would lead to new ways to detect benefits of exercise on cognitive aging and would lead to mechanistic insight on how such plasticity is possible while also informing prevention strategies.
Detailed Description Animal models robustly support that exercise protects brain areas vulnerable to aging such as the hippocampus and that these benefits lead to better learning. In contrast, there are mixed findings from human studies on the cognitive benefits of exercise with healthy older adults. This contrast indicates there is still a lack of understanding for how exercise could change the course of cognitive decline in aging adults. However, no human studies have comprehensively tested exercise effects on cognition in older adults with learning tasks inspired from basic exercise neuroscience. The objective in the proposed research is to fill this translational gap by determining if different types of exercise improve the same kinds of learning in older adults that have been shown to improve in animal models by improving hippocampal function. This will bring the investigators closer to a long-term goal of determining how exercise protects the brain from adverse effects of aging in order to develop interventions that minimize age-related cognitive decline. The overall hypothesis is that exercise improves learning when it increases functional hippocampal-cortical communication that otherwise declines with aging. The investigators will test this in a sample of healthy older adults by determining if increases in functional hippocampal-cortical connectivity from exercise training improve learning on an array of tasks that require the hippocampus for acquisition of new relational memories compared to conditions of the same tasks that should not require the hippocampus for learning and memory.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE Sedentary Lifestyle
Intervention  ICMJE
  • Behavioral: Cardiorespiratory fitness training
    Physical exercise of moderate intensity designed to improve cardiorespiratory fitness
  • Behavioral: Functional fitness training
    Physical exercise of light intensity designed to improve functional fitness
Study Arms  ICMJE
  • Experimental: Cardiorespiratory fitness training
    Cardiorespiratory fitness training will be a 24-week supervised cycling program designed to improve cardiorespiratory fitness, with supervision directly from the research team. All participants will first receive a one-on-one orientation with an exercise training specialist that has been trained by Dr. Gary Pierce in monitoring an exercise program for healthy older adults. Training will start with a 5 minute-warm-up, 20 minutes moderate intensity cycling and 30 minutes light intensity cycling, and 5 minute cool-down per session, for 3 sessions/week. In each additional week, 6 minutes of moderate intensity cycling per session will be added, until the total time for moderate intensity is 50 minutes per session by the start of week 5 (with additional 5 minute warm-up and 5 minute cool-down).
    Intervention: Behavioral: Cardiorespiratory fitness training
  • Active Comparator: Functional fitness training
    Functional fitness training will be a 24-week supervised exercise program designed to focus on functional flexibility and mobility, with supervision directly from our research team. All participants will first receive a one-on-one orientation with an exercise training specialist that has been trained by Dr. Gary Pierce in monitoring an exercise program for healthy older adults. Training will start with a 5 minute-warm-up, 20 minutes of light intensity cycling and 20 minutes of dynamic stretching to increase range of motion and functional fitness, for 3 sessions/week. In each additional week, additional stretches will be added to maintain variety and improve flexibility of all major muscle groups.
    Intervention: Behavioral: Functional fitness training
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 10, 2017)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Eligible to participate in an aerobic exercise intervention based on the Physical Activity Readiness Questionnaire, and corrected vision of 20/40.
  • Approval from a physician that monitored electrocardiography (ECG) response during a maximal aerobic fitness test that is part of the second study visit described below.
  • Exercising less than 60 minutes a week for the past calendar year

Exclusion Criteria:

  • Not between the ages of 55 and 80 years old
  • Not fluent in English
  • Score < 20 (out of 30) on the Montreal Cognitive Assessment (MoCA)
  • Inability to comply with experimental instructions
  • Qualify as "high risk" for acute cardiovascular event by the published standards of the American College of Sports Medicine
  • Previous diagnosis of neurological, metabolic, or psychiatric condition, and no previous brain injury associated with loss of consciousness
  • Inability to complete an MRI
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 55 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Michelle W Voss, PhD 319-335-2057 michelle-voss@uiowa.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03114150
Other Study ID Numbers  ICMJE 201705800
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: In accord with NIH regulations, the investigators will make the data and relevant documentation available to other investigators upon acceptance of the main findings from the study for publication. The investigators will share analysis tools as they are developed. Because the collected data are to remain anonymous, only a subject number will identify all data. To further protect the privacy and confidentiality of the data, data and documentation will be made available only under a data-sharing agreement that provides for restrictions for the transferring of data to others and a commitment that the data will be used for research purposes only and not for a profit-making enterprise.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Analytic Code
Time Frame: We will share baseline neuroimaging data and phenotypic data upon completion of data collection. We will share the intervention outcome data after we have published our results from each primary aim.
Access Criteria: We will share on an open platform such as OpenNeuro (https://openneuro.org/).
Responsible Party Michelle W. Voss, University of Iowa
Study Sponsor  ICMJE Michelle W. Voss
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Michelle W Voss, PhD University of Iowa
PRS Account University of Iowa
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP