AgingNCT03803904
Aerobic Exercise and Cerebrovascular Function
A study testing Spin in people with Aging, run by VA Office of Research and Development at 1 site in United States.
Trial summary
This proposal will evaluate two brain health measures, cerebrovascular perfusion and cerebrovascular reactivity (CVR), before and after a proven, interval-based, aerobic exercise intervention in older Veterans. Read more about this study
- Who is it for?
- Ages 65 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Aging
- What is being tested?
- Spin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2019to 15 Jan 2026
- 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 65 to 80 years
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- Adults aged 65-80 who do not regularly exercise
- defined as exercising less than 20 minutes twice per week
- Are willing and able to cooperate with assessments and interventions
- Participant will be quantified at or below the "poor" range for cardiovascular fitness as assessed by a volume of oxygen (VO2) test
- 26.0 ml/kg/min for males
- 21.0 ml/kg/min for females)
Show all 18Show fewer
- 26 on the MoCA to meet the criteria for cognitively intact
- Participants will be free from diseases affecting cognition or that would interfere with their ability to engage in aerobic exercise - including but not limited to:
- chronic heart
- liver
- kidney disease
- Free from diseases/injuries directly affecting brain functions - including but not limited to:
- significant closed head injury
- open intracranial wounds
- stroke
- epilepsy
- degenerative diseases of the nervous system
- All subjects will speak English as a primary language and will have at minimum a high school diploma so that behavioral/cognitive measures reflect effects of aging and aerobic exercise and not unfamiliarity with the English language or a lack of education
Who cannot join
- Potential participants with major psychiatric disorder - including but not limited to:
- psychosis
- major depression
- bipolar disorder
- Individuals with ongoing drug or alcohol abuse and severe hypertension (systolic BP > 200 or diastolic BP > 110 mm Hg or subjects taking three or more antihypertensive medications
- Participants must not have conditions incompatible with MRI - including but not limited to:
Show all 11Show fewer
- ferrous metal implants
- cardiac pacemakers or similar devices
- claustrophobia
- morbid obesity
- Persons engaging in significant skilled manual movements regularly will be excluded so that behavioral/motor measures reflect the effects of age and aerobic exercise and not the effects of frequent practice
Trial locations and contacts
1 site in 1 country.
United States1 site
Atlanta VA Medical and Rehab Center, Decatur, GA
Decatur, Georgia, 30033-4004
About this study
Official title: Graded Intensity Aerobic Exercise to Improve Cerebrovascular Function and Performance in Aged Veterans
This proposal will evaluate two brain health measures, cerebrovascular perfusion and cerebrovascular reactivity (CVR), before and after a proven, interval-based, aerobic exercise intervention in older Veterans. The hypothesis is that the 12-week aerobic exercise intervention (Spin) will increase perfusion and improve CVR in brain regions susceptible to age-related decline. This information will inform the impact of exercise on cerebrovascular health which is known to be negatively impacted in aging and implicated in the development of neurodegenerative disease. This information will also aid the investigators' continued efforts of clinical implementation of evidence-based exercise interventions in the local Atlanta VA and surround region.
Read the detailed description
To address the growing healthcare challenges of an aging Veteran population it is critical to understand effective rehabilitation techniques that mitigate age-related co-morbidity and improve quality of life. To date, exercise is one of a few proven interventions that attenuates age-related declines in brain health and function. A consistent but unexplained finding in many of these studies is a change in the cortical activation pattern during task, assessed using blood-oxygen-level dependent (BOLD) signal with fMRI that corresponds with improved task performance. Two key metrics of cerebrovascular health and functioning that are unexplored but may influence the documented changes in the BOLD response that is observed with post-aerobic activity are: 1) changes in resting or basal cerebral blood flow (perfusion) to key brain regions; and 2) changes in the ability of cerebrovasculature to dilate in the face of increased demand, termed cerebrovascular reactivity (CVR). The investigators' goal is to quantify the impact of aerobic exercise on cerebrovascular function and how both perfusion and CVR contributes to the BOLD signal during task-based fMRI. Consistent with the investigators' previous aging and exercise studies participants will complete one of two conditions; 1) an aerobic, interval-training intervention (Spin; n= 44), or 2) a non-aerobic, stretching control condition (Control; n=44). Cardiovascular fitness, arterial spin labeling for basal cerebral perfusion, CVR, task-based fMRI (cognitive-executive and motor), and behavioral outcomes will be assessed before and after the interventions. The specific aims will determine the effect of a 12-week aerobic exercise intervention on changes in cerebral perfusion and CVR in older Veterans. The investigators hypothesize that compared to the Control group, the aerobically-trained group will have increased basal perfusion and CVR in areas that demonstrate age-related decline and that have been demonstrated to be malleable to aerobic exercise (inferior frontal and motor cortices).
Research over the last few decades have driven the continual promotion of exercise as one of the most impactful interventions of central nervous system health and function. At the forefront of much of this research is the use of task-based fMRI BOLD to quantify beneficial changes in cortical function following aerobic exercise. While transformative, the true impact of this research is limited in scope until the investigators can define the influence of cerebrovascular function on the well-documented beneficial change in BOLD response. The investigators do know that older adults who are physically active have improved vascular health but do not know the full impact of an exercise intervention on cerebrovascular health. If the hypotheses of improved perfusion and CVR is supported it would inform current intervention strategies and would add important additional information about the potential of exercise to improve brain health in aging. This would have implications for aging Veterans at risk for neurodegenerative disease brought on by cerebrovascular dysfunction.
- Conditions
- Aging
- Being tested
- Spin
- Keywords
- exercise, brain health
- Medical subject headings
- Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SpinOther
The intervention will take place three times a week for 12 weeks and will be led by a qualified instructor (an Exercise Physiologist with five years of experience conducting the intervention). The duration of each session will be increased by 1-2 minutes to a maximum time of 45 minutes per session based on the progression of the participants and the recommendation of the instructor. Because participants are initially sedentary and detrained, exercise intensity will begin at low levels (50% of maximal heart rate reserve, HRR) but will be increased by 5% every week (if deemed necessary by the instructor) to a maximum of 75% maximal HRR.
| Study group | Role | What they receive |
|---|---|---|
| Spin | Experimental | The intervention will take place three times a week for 12 weeks and will be led by a qualified instructor (an Exercise Physiologist with five years of experience conducting the intervention). The duration of each session will be increased by 1-2 minutes to a maximum time of 45 minutes per session based on the progression of the participants and the recommendation of the instructor. Because participants are initially sedentary and detrained, exercise intensity will begin at low levels (50% of maximal heart rate reserve, HRR) but will be increased by 5% every week (if deemed necessary by the instructor) to a maximum of 75% maximal HRR. Receives: Other: Spin |
| Control | Active comparator | Participants in the control group will be equalized (frequency and duration) to the Spin group for contact and monitoring. As such they will report to the same facility and interact with the same experienced interventionist; however instead of progressive Spin exercise they will participate in sessions focused on balance and stretching. Similar to the aerobic intervention, these exercises will take place in a group setting and heart rate will be consistently monitored during each session to verify heart rate does not reach 50% HRR. Receives: Other: Spin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cerebrovascular Reactivity (CVR) Using a Hypercapnic CO2 Response Test Change
CVR will be assessed using 5% CO2 challenge while continuously acquiring MR images. This method has been extensively used and is the most suitable vasoactive stimulus. Briefly, the CO2 air (5% CO2, 21% O2 and 74% N2) will be administered via an air bag with a valve to switch between room air and CO2 air in the bag. A mouth piece and a nose clip will be used to achieve mouth-only breathing. A research staff member will be inside the magnet room throughout the experiment to switch the valve and to monitor the subject. Physiologic parameters, including end-tidal (Et) CO2 and breathing rate will be monitored and recorded during the experiments. The percentage of change in Blood-Oxygen-Level-Dependent (BOLD) signal per millimeter of mercury is the metric used to quantify CVR. It measures how much the BOLD signal changes in response to a 1 mmHg change in the end-tidal partial pressure of carbon dioxide.
Measured: At the Pre-intervention assessment and 12-weeks following at the Post intervention assessment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2019
- Study start1 Apr 2019
- Primary completion1 Jun 2025
- Study completion15 Jan 2026
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 AgingStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Joe R. Nocera, PhD, Principal investigator, Atlanta VA Medical and Rehab Center, Decatur, GA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03803904
- Sponsor's protocol ID
- E2825-R
- Status last verified
- May 2026
- First submitted
- 9 Jan 2019
- Last updated
- 9 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Graded Intensity Aerobic Exercise to Improve Cerebrovascular Function and Performance in Aged Veterans
- ClinicalTrials.gov ID
- NCT03803904
- Acronym / sponsor ID
- E2825-R
- Conditions
- Aging
- Keywords
- exercise, brain health
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 1 Apr 2019 (actual)
- Primary completion
- 1 Jun 2025 (actual)
- Study completion
- 15 Jan 2026 (actual)
- First posted
- 15 Jan 2019 (actual)
- Results
- Posted 5 Mar 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This proposal will evaluate two brain health measures, cerebrovascular perfusion and cerebrovascular reactivity (CVR), before and after a proven, interval-based, aerobic exercise intervention in older Veterans. The hypothesis is that the 12-week aerobic exercise intervention (Spin) will increase perfusion and improve CVR in brain regions susceptible to age-related decline. This information will inform the impact of exercise on cerebrovascular health which is known to be negatively impacted in aging and implicated in the development of neurodegenerative disease. This information will also aid the investigators' continued efforts of clinical implementation of evidence-based exercise interventions in the local Atlanta VA and surround region.
Detailed description
To address the growing healthcare challenges of an aging Veteran population it is critical to understand effective rehabilitation techniques that mitigate age-related co-morbidity and improve quality of life. To date, exercise is one of a few proven interventions that attenuates age-related declines in brain health and function. A consistent but unexplained finding in many of these studies is a change in the cortical activation pattern during task, assessed using blood-oxygen-level dependent (BOLD) signal with fMRI that corresponds with improved task performance. Two key metrics of cerebrovascular health and functioning that are unexplored but may influence the documented changes in the BOLD response that is observed with post-aerobic activity are: 1) changes in resting or basal cerebral blood flow (perfusion) to key brain regions; and 2) changes in the ability of cerebrovasculature to dilate in the face of increased demand, termed cerebrovascular reactivity (CVR). The investigators' goal is to quantify the impact of aerobic exercise on cerebrovascular function and how both perfusion and CVR contributes to the BOLD signal during task-based fMRI. Consistent with the investigators' previous aging and exercise studies participants will complete one of two conditions; 1) an aerobic, interval-training intervention (Spin; n= 44), or 2) a non-aerobic, stretching control condition (Control; n=44). Cardiovascular fitness, arterial spin labeling for basal cerebral perfusion, CVR, task-based fMRI (cognitive-executive and motor), and behavioral outcomes will be assessed before and after the interventions. The specific aims will determine the effect of a 12-week aerobic exercise intervention on changes in cerebral perfusion and CVR in older Veterans. The investigators hypothesize that compared to the Control group, the aerobically-trained group will have increased basal perfusion and CVR in areas that demonstrate age-related decline and that have been demonstrated to be malleable to aerobic exercise (inferior frontal and motor cortices).
Research over the last few decades have driven the continual promotion of exercise as one of the most impactful interventions of central nervous system health and function. At the forefront of much of this research is the use of task-based fMRI BOLD to quantify beneficial changes in cortical function following aerobic exercise. While transformative, the true impact of this research is limited in scope until the investigators can define the influence of cerebrovascular function on the well-documented beneficial change in BOLD response. The investigators do know that older adults who are physically active have improved vascular health but do not know the full impact of an exercise intervention on cerebrovascular health. If the hypotheses of improved perfusion and CVR is supported it would inform current intervention strategies and would add important additional information about the potential of exercise to improve brain health in aging. This would have implications for aging Veterans at risk for neurodegenerative disease brought on by cerebrovascular dysfunction.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Spin | Experimental | Other: SpinThe intervention will take place three times a week for 12 weeks and will be led by a qualified instructor (an Exercise Physiologist with five years of experience conducting the intervention). The duration of each session will be increased by 1-2 minutes to a maximum time of 45 minutes per session based on the progression of the participants and the recommendation of the instructor. Because participants are initially sedentary and detrained, exercise intensity will begin at low levels (50% of maximal heart rate reserve, HRR) but will be increased by 5% every week (if deemed necessary by the instructor) to a maximum of 75% maximal HRR. |
| Control | Active comparator | Other: SpinParticipants in the control group will be equalized (frequency and duration) to the Spin group for contact and monitoring. As such they will report to the same facility and interact with the same experienced interventionist; however instead of progressive Spin exercise they will participate in sessions focused on balance and stretching. Similar to the aerobic intervention, these exercises will take place in a group setting and heart rate will be consistently monitored during each session to verify heart rate does not reach 50% HRR. |
Who may qualify
- Ages
- 65 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (18 listed)
- Adults aged 65-80 who do not regularly exercise
- Are willing and able to cooperate with assessments and interventions
- Participant will be quantified at or below the "poor" range for cardiovascular fitness as assessed by a volume of oxygen (VO2) test
- 26 on the MoCA to meet the criteria for cognitively intact
- Participants will be free from diseases affecting cognition or that would interfere with their ability to engage in aerobic exercise - including but not limited to:
Key exclusion criteria (11 listed)
- Potential participants with major psychiatric disorder - including but not limited to:
- Individuals with ongoing drug or alcohol abuse and severe hypertension (systolic BP > 200 or diastolic BP > 110 mm Hg or subjects taking three or more antihypertensive medications
- Participants must not have conditions incompatible with MRI - including but not limited to:
- Persons engaging in significant skilled manual movements regularly will be excluded so that behavioral/motor measures reflect the effects of age and aerobic exercise and not the effects of frequent practice
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 |
|---|---|---|
| SpinThe intervention will take place three times a week for 12 weeks and will be led by a qualified instructor (an Exercise Physiologist with five years of experience conducting the intervention). The duration of each session will be increased by 1-2 minutes to a maximum time of 45 minutes per session based on the progression of the participants and the recommendation of the instructor. Because participants are initially sedentary and detrained, exercise intensity will begin at low levels (50% of maximal heart rate reserve, HRR) but will be increased by 5% every week (if deemed necessary by the instructor) to a maximum of 75% maximal HRR. | Other | Control, Spin |
Primary outcome
Cerebrovascular Reactivity (CVR) Using a Hypercapnic CO2 Response Test Change
Time frame: At the Pre-intervention assessment and 12-weeks following at the Post intervention assessment
CVR will be assessed using 5% CO2 challenge while continuously acquiring MR images. This method has been extensively used and is the most suitable vasoactive stimulus. Briefly, the CO2 air (5% CO2, 21% O2 and 74% N2) will be administered via an air bag with a valve to switch between room air and CO2 air in the bag. A mouth piece and a nose clip will be used to achieve mouth-only breathing. A research staff member will be inside the magnet room throughout the experiment to switch the valve and to monitor the subject. Physiologic parameters, including end-tidal (Et) CO2 and breathing rate will be monitored and recorded during the experiments. The percentage of change in Blood-Oxygen-Level-Dependent (BOLD) signal per millimeter of mercury is the metric used to quantify CVR. It measures how much the BOLD signal changes in response to a 1 mmHg change in the end-tidal partial pressure of carbon dioxide.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Joe R. Nocera, PhD principal investigator
Atlanta VA Medical and Rehab Center, Decatur, GA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Spin in people with Aging, run by VA Office of Research and Development 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 18 inclusion and 11 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 9 Jun 2026. 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 5 Mar 2026). 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?
Cerebrovascular Reactivity (CVR) Using a Hypercapnic CO2 Response Test Change (time frame: At the Pre-intervention assessment and 12-weeks following at the Post intervention assessment). 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 9 Jun 2026.