Sedentary LifestyleEXTENDNCT03114150
Exercise Effects on Brain Health and Learning From Minutes to Months
A study testing Cardiorespiratory fitness training and Functional fitness training in people with Sedentary Lifestyle, run by Michelle W. Voss at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 55 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Sedentary Lifestyle
- What is being tested?
- Cardiorespiratory fitness training and Functional fitness training
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 122 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2018to 21 Jun 2023
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Exercise to Improve Hippocampal Connectivity and Learning in Older Adults
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.
Read the 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.
- Conditions
- Sedentary Lifestyle
- Being tested
- Cardiorespiratory fitness training, Functional fitness training
- Keywords
- physical activity, aging, learning and memory, exercise, brain
- Medical subject headings
- Sedentary Behavior, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cardiorespiratory fitness trainingBehavioural
Physical exercise of moderate intensity designed to improve cardiorespiratory fitness
Functional fitness trainingBehavioural
Physical exercise of light intensity designed to improve functional fitness
| Study group | Role | What they receive |
|---|---|---|
| Cardiorespiratory fitness training | Experimental | 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). Receives: Behavioral: Cardiorespiratory fitness training |
| Functional fitness training | Active comparator | 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. Receives: Behavioral: Functional fitness training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Hippocampal-dependent Learning
Learning rate on constructs that have been examined in animal models including context acquisition, episodic associations, and spatial navigation. The primary outcome is reported for the spatial navigation task that is associated with hippocampal structure and function, which is learning in the wayfinding condition. We report change in slope for wayfinding learning trials. The slope is computed based on the proportion of items correctly recalled on a map, over four learning trials. For each trial, proportion correct can range from 0 to 1, and a higher number represents faster learning, which is better.
Measured: Baseline, 24-weeks
Secondary outcomes (3)
Change in Hippocampal-cortical Functional Connectivity
The change in 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.
Measured: Baseline, 30 minutes
Change in Hippocampal-cortical Functional Connectivity
The change in 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.
Measured: Baseline, 24-weeks
Change in Cardiorespiratory Fitness
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 maximal VO2 is reported for descriptive results.
Measured: Baseline, 24-weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2017
- Study start1 May 2018
- Primary completion21 Jun 2023
- Study completion21 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Sedentary LifestyleStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 122 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michelle W. Voss
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor-investigator, Michelle W. Voss, University of Iowa
- Investigators
- Michelle W Voss, PhD, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03114150
- Sponsor's protocol ID
- 201705800
- Other IDs
- 1R01AG055500-01
- Acronym
- EXTEND
- Status last verified
- Jul 2025
- First submitted
- 30 Mar 2017
- Last updated
- 13 Aug 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exercise to Improve Hippocampal Connectivity and Learning in Older Adults
- ClinicalTrials.gov ID
- NCT03114150
- Acronym / sponsor ID
- EXTEND / 201705800
- Conditions
- Sedentary Lifestyle
- Keywords
- physical activity, aging, learning and memory, exercise, brain
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 122 participants (actual)
- Lead sponsor
- Michelle W. VossUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 1 May 2018 (actual)
- Primary completion
- 21 Jun 2023 (actual)
- Study completion
- 21 Jun 2023 (actual)
- First posted
- 14 Apr 2017 (actual)
- Results
- Posted 13 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cardiorespiratory fitness training | Experimental | Behavioral: Cardiorespiratory fitness trainingCardiorespiratory 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). |
| Functional fitness training | Active comparator | Behavioral: Functional fitness trainingFunctional 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. |
Who may qualify
- Ages
- 55 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cardiorespiratory fitness trainingPhysical exercise of moderate intensity designed to improve cardiorespiratory fitness | Behavioural | Cardiorespiratory fitness training |
| Functional fitness trainingPhysical exercise of light intensity designed to improve functional fitness | Behavioural | Functional fitness training |
Primary outcome
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. The primary outcome is reported for the spatial navigation task that is associated with hippocampal structure and function, which is learning in the wayfinding condition. We report change in slope for wayfinding learning trials. The slope is computed based on the proportion of items correctly recalled on a map, over four learning trials. For each trial, proportion correct can range from 0 to 1, and a higher number represents faster learning, which is better.
3 secondary outcomes
Change in Hippocampal-cortical Functional Connectivity
Time frame: Baseline, 30 minutes
Change in Hippocampal-cortical Functional Connectivity
Time frame: Baseline, 24-weeks
Change in Cardiorespiratory Fitness
Time frame: Baseline, 24-weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michelle W Voss, PhD principal investigator
University of Iowa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cardiorespiratory fitness training and Functional fitness training in people with Sedentary Lifestyle, run by Michelle W. Voss at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Hippocampal-dependent Learning (time frame: Baseline, 24-weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2025.