Alzheimer Disease 2 Due to Apoe4 IsoformDYNAMICNCT04009629
Dementia Risk and Dynamic Response to Exercise
A study testing Moderate Intensity Aerobic Exercise in people with Alzheimer Disease 2 Due to Apoe4 Isoform and Healthy Aging, run by University of Kansas Medical Center at 1 site in United States.
Trial summary
Research suggests that physical exercise supports brain health and cognition as we age. The goal of this project is to examine the specific changes in brain blood flow and biological factors in the blood immediately after exercise in older adults who have the APOE4 gene, a genetic risk factor for developing… Read more about this study
- Who is it for?
- Ages 65 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease 2 Due to Apoe4 Isoform, Healthy Aging
- What is being tested?
- Moderate Intensity Aerobic Exercise
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Oct 2019to 28 Oct 2021
- 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 85 years
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- Age 65-85
- English speaking
- Normal or corrected hearing or vision,
- Without activity restrictions.
Who cannot join
- Clinically significant cognitive or psychiatric illness,
- Anti- coagulant use,
- High cardiovascular risk without physician clearance for exercise,
- Exercise-limiting musculoskeletal condition,
- MRI contraindications
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Kansas Alzheimer's Disease Center
Fairway, Kansas, 66205
About this study
Research suggests that physical exercise supports brain health and cognition as we age. The goal of this project is to examine the specific changes in brain blood flow and biological factors in the blood immediately after exercise in older adults who have the APOE4 gene, a genetic risk factor for developing Alzheimer's. Results from this study will help researchers and clinicians understand and measure changes in the body and brain as a function of exercise, and how those changes relate to Alzheimer's risk.
Read the detailed description
The brain and cardiovascular system share common risk factors for age-related diseases such as hypertension, hypercholesterolemia, and genetics (e.g. APOE4). Because of this link, much work has focused on the role of cerebrovascular health in reducing dementia risk. Regular aerobic exercise has well-established benefits for cardiovascular health and has been repeatedly linked to better cognition, brain health, and lower risk of Alzheimer's disease (AD). Despite strong evidence for sustained cognitive and brain outcomes, the mechanisms relating aerobic exercise with brain health and cognition remain imprecisely defined. Amongst many potential mechanisms, cerebral blood flow (CBF) and blood-based biomarkers, such as neurotrophins, are promising targets for their shared association to brain and cardiovascular health. Prior investigations have largely attempted to measure change in these mechanisms under resting conditions after an extended exercise intervention with mixed and conflicting results. Further, studies have often not accounted for genetic differences that may blunt the effect of exercise. Unlike prior work, our innovative approach is to begin by characterizing the dynamic changes that result from an acute exercise challenge. A single bout of aerobic exercise temporarily increases CBF and prompts neurotrophin release. These transient changes ultimately drive long-term physiologic adaptation to exercise. Therefore, the study team will characterize the dynamic response to an acute, standardized bout of aerobic exercise in a group of nondemented older adults, comparing those who do and do not carry the APOE4 allele. The first aim will test if CBF response to an acute exercise challenge is blunted in APOE4 carriers. The second aim will similarly test the acute exercise response of blood-based biomarkers such as brain derived neurotrophic factor, insulin-like growth factor, and vascular endothelial growth factor in APOE4 carriers versus non-carriers. The study team expects that more accurately understanding the acute effects will provide valuable insight into how aerobic exercise supports cognitive function and brain health. Armed with this knowledge the field can optimize biomarker measurement for future exercise intervention randomized controlled trials, informing our long-term goal of identifying precision exercise prescription for AD prevention.
- Being tested
- Moderate Intensity Aerobic Exercise
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Moderate Intensity Aerobic ExerciseBehavioural
Participants will exercise for 15 minutes in a moderate age-predicted heart rate range. The study team will employ an exercise device such as a treadmill, cycle, or recumbent stepper to maintain control over workload.
| Study group | Role | What they receive |
|---|---|---|
| Exercise - apolipoprotein e4 carrier | Experimental | A single 15 minute bout of moderate intensity aerobic exercise for individuals with 1 or 2 copies of the APOE4 allele, the leading genetic risk factor for late-onset Alzheimer's dementia. Receives: Behavioral: Moderate Intensity Aerobic Exercise |
| Exercise - apolipoprotein e4 non-carrier | Experimental | A single 15 minute bout of moderate intensity aerobic exercise for individuals with 0 copies of the APOE4 allele, the leading genetic risk factor for late-onset Alzheimer's dementia. Receives: Behavioral: Moderate Intensity Aerobic Exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cerebral Blood Flow Area Under Curve
Cumulative cerebral blood flow measured by Arterial Spin Labeling MRI. The standard arterial spin labeling unit of measure is average milliliters per 100 grams of tissue per minute (mL/100g tissue/minute). For the present analysis, we summed perfusion over the entire acquisition period, 23.2 minutes, rather than averaging. Therefore the units are milliliters per 100 grams of tissue
Measured: ~24 minutes
Secondary outcomes (3)
Insulin-like Growth Factor-1 Change
Change in circulating Insulin-like Growth Factor-1 from pre-to-post exercise
Measured: Pre-to-post intervention (~15 minutes)
Vascular Endothelial Growth Factor Change
Change in circulating Vascular Endothelial Growth Factor from pre-to-post exercise
Measured: Pre-to-post intervention (~15 minutes)
Brain Derived Neurotrophic Factor Change
Change in circulating Brain Derived Neurotrophic Factor from pre-to-post exercise
Measured: Pre-to-post intervention (~15 minutes)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jul 2019
- Study start25 Oct 2019
- Primary completion28 Oct 2021
- Study completion28 Oct 2021
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Alzheimer Disease 2 Due to Apoe4 IsoformStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Single visit, case-control study identified as an intervention due to the use of a single bout of aerobic exercise under NIH rules (grants.nih.gov/policy/clinical-trials/definition.htm)
- Masking
- None (open label)
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Kansas Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Eric D Vidoni, PT, PHD, Principal investigator, University of Kansas Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04009629
- Sponsor's protocol ID
- STUDY00142822
- Other IDs
- R21AG061548
- Acronym
- DYNAMIC
- Status last verified
- May 2022
- First submitted
- 2 Jul 2019
- Last updated
- 3 May 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified data may be shared with unaffiliated investigators after completion of data collection and a reasonable amount of analysis and dissemination time. Contact the PI for further information.
Publications
Vidoni ED, Morris JK, Palmer JA, Li Y, White D, Kueck PJ, John CS, Honea RA, Lepping RJ, Lee P, Mahnken JD, Martin LE, Billinger SA. Dementia risk and dynamic response to exercise: A non-randomized clinical trial. PLoS One. 2022 Jul 8;17(7):e0265860. doi: 10.1371/journal.pone.0265860. eCollection 2022.
PubMed 35802628White D, John CS, Kucera A, Truver B, Lepping RJ, Kueck PJ, Lee P, Martin L, Billinger SA, Burns JM, Morris JK, Vidoni ED. A methodology for an acute exercise clinical trial called dementia risk and dynamic response to exercise. Sci Rep. 2021 Jun 17;11(1):12776. doi: 10.1038/s41598-021-92177-0.
PubMed 34140586
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dementia Risk and Dynamic Response to Exercise
- ClinicalTrials.gov ID
- NCT04009629
- Acronym / sponsor ID
- DYNAMIC / STUDY00142822
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- University of Kansas Medical CenterUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 25 Oct 2019 (actual)
- Primary completion
- 28 Oct 2021 (actual)
- Study completion
- 28 Oct 2021 (actual)
- First posted
- 5 Jul 2019 (actual)
- Results
- Posted 3 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Research suggests that physical exercise supports brain health and cognition as we age. The goal of this project is to examine the specific changes in brain blood flow and biological factors in the blood immediately after exercise in older adults who have the APOE4 gene, a genetic risk factor for developing Alzheimer's. Results from this study will help researchers and clinicians understand and measure changes in the body and brain as a function of exercise, and how those changes relate to Alzheimer's risk.
Detailed description
The brain and cardiovascular system share common risk factors for age-related diseases such as hypertension, hypercholesterolemia, and genetics (e.g. APOE4). Because of this link, much work has focused on the role of cerebrovascular health in reducing dementia risk. Regular aerobic exercise has well-established benefits for cardiovascular health and has been repeatedly linked to better cognition, brain health, and lower risk of Alzheimer's disease (AD). Despite strong evidence for sustained cognitive and brain outcomes, the mechanisms relating aerobic exercise with brain health and cognition remain imprecisely defined. Amongst many potential mechanisms, cerebral blood flow (CBF) and blood-based biomarkers, such as neurotrophins, are promising targets for their shared association to brain and cardiovascular health. Prior investigations have largely attempted to measure change in these mechanisms under resting conditions after an extended exercise intervention with mixed and conflicting results. Further, studies have often not accounted for genetic differences that may blunt the effect of exercise. Unlike prior work, our innovative approach is to begin by characterizing the dynamic changes that result from an acute exercise challenge. A single bout of aerobic exercise temporarily increases CBF and prompts neurotrophin release. These transient changes ultimately drive long-term physiologic adaptation to exercise. Therefore, the study team will characterize the dynamic response to an acute, standardized bout of aerobic exercise in a group of nondemented older adults, comparing those who do and do not carry the APOE4 allele. The first aim will test if CBF response to an acute exercise challenge is blunted in APOE4 carriers. The second aim will similarly test the acute exercise response of blood-based biomarkers such as brain derived neurotrophic factor, insulin-like growth factor, and vascular endothelial growth factor in APOE4 carriers versus non-carriers. The study team expects that more accurately understanding the acute effects will provide valuable insight into how aerobic exercise supports cognitive function and brain health. Armed with this knowledge the field can optimize biomarker measurement for future exercise intervention randomized controlled trials, informing our long-term goal of identifying precision exercise prescription for AD prevention.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Single visit, case-control study identified as an intervention due to the use of a single bout of aerobic exercise under NIH rules (grants.nih.gov/policy/clinical-trials/definition.htm)
| Arm | Type | Receives |
|---|---|---|
| Exercise - apolipoprotein e4 carrier | Experimental | Behavioral: Moderate Intensity Aerobic ExerciseA single 15 minute bout of moderate intensity aerobic exercise for individuals with 1 or 2 copies of the APOE4 allele, the leading genetic risk factor for late-onset Alzheimer's dementia. |
| Exercise - apolipoprotein e4 non-carrier | Experimental | Behavioral: Moderate Intensity Aerobic ExerciseA single 15 minute bout of moderate intensity aerobic exercise for individuals with 0 copies of the APOE4 allele, the leading genetic risk factor for late-onset Alzheimer's dementia. |
Who may qualify
- Ages
- 65 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (4 listed)
- Age 65-85
- English speaking
- Normal or corrected hearing or vision,
- Without activity restrictions.
Key exclusion criteria (5 listed)
- Clinically significant cognitive or psychiatric illness,
- Anti- coagulant use,
- High cardiovascular risk without physician clearance for exercise,
- Exercise-limiting musculoskeletal condition,
- MRI contraindications
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 |
|---|---|---|
| Moderate Intensity Aerobic ExerciseParticipants will exercise for 15 minutes in a moderate age-predicted heart rate range. The study team will employ an exercise device such as a treadmill, cycle, or recumbent stepper to maintain control over workload. | Behavioural | Exercise - apolipoprotein e4 carrier, Exercise - apolipoprotein e4 non-carrier |
Primary outcome
Cerebral Blood Flow Area Under Curve
Time frame: ~24 minutes
Cumulative cerebral blood flow measured by Arterial Spin Labeling MRI. The standard arterial spin labeling unit of measure is average milliliters per 100 grams of tissue per minute (mL/100g tissue/minute). For the present analysis, we summed perfusion over the entire acquisition period, 23.2 minutes, rather than averaging. Therefore the units are milliliters per 100 grams of tissue
3 secondary outcomes
Insulin-like Growth Factor-1 Change
Time frame: Pre-to-post intervention (~15 minutes)
Vascular Endothelial Growth Factor Change
Time frame: Pre-to-post intervention (~15 minutes)
Brain Derived Neurotrophic Factor Change
Time frame: Pre-to-post intervention (~15 minutes)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35802628Vidoni ED, Morris JK, Palmer JA, Li Y, White D, Kueck PJ, John CS, Honea RA, Lepping RJ, Lee P, Mahnken JD, Martin LE, Billinger SA. Dementia risk and dynamic response to exercise: A non-randomized clinical trial. PLoS One. 2022 Jul 8;17(7):e0265860. doi: 10.1371/journal.pone.0265860. eCollection 2022.
- Derived from this study: PubMed 34140586White D, John CS, Kucera A, Truver B, Lepping RJ, Kueck PJ, Lee P, Martin L, Billinger SA, Burns JM, Morris JK, Vidoni ED. A methodology for an acute exercise clinical trial called dementia risk and dynamic response to exercise. Sci Rep. 2021 Jun 17;11(1):12776. doi: 10.1038/s41598-021-92177-0.
- Individual participant dataSharing planned: Yes. De-identified data may be shared with unaffiliated investigators after completion of data collection and a reasonable amount of analysis and dissemination time. Contact the PI for further information.
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.
Eric D Vidoni, PT, PHD principal investigator
University of Kansas Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Moderate Intensity Aerobic Exercise in people with Alzheimer Disease 2 Due to Apoe4 Isoform and Healthy Aging, run by University of Kansas Medical Center 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 4 inclusion and 5 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 3 May 2022. 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 3 May 2022). 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?
Cerebral Blood Flow Area Under Curve (time frame: ~24 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04009629, which also lists 2 linked publications.
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 3 May 2022; AzTrials last refreshed its copy on 27 Oct 2026.