High Intensity ExerciseCYCLE-ADNCT04748861
CYCLE-AD (CYcling to Cease or Limit the Effects of Alzheimer's Disease)
A study testing Indoor Cycling (IC) in people with High Intensity Exercise and Normal Cognition, run by The Cleveland Clinic at 1 site in United States.
Trial summary
The overall goal of the CYCLE-AD trial is to determine the role of long-term, high intensity exercise in slowing or delaying the onset of cognitive and AD-related brain changes in e4 carriers. Read more about this study
- Who is it for?
- Ages 65 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- High Intensity Exercise, Normal Cognition, Exercise Intervention
- What is being tested?
- Indoor Cycling (IC)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Oct 2021to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- Healthy elders, ages 65-80 years, inclusive
- No cognitive impairment based on screening examination
- APOE ε4 genotype
- Inactive; defined as exercising less than 3x per week at moderate-vigorous intensity
- Fluent in English (a requirement for neurocognitive testing)
- Does not plan to travel for more than 2 consecutive weeks over the course of the study
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- Demonstrate ability to safely mount and dismount Peloton stationary cycle
- In-home Wi-Fi (Peloton system requires Wi-Fi to transmit exercise data)
- Medical clearance by the study doctor to participate in exercise program
- Participant must meet Peloton height and weight safety requirements
Who cannot join
- Any significant neurologic disease, including dementia, mild cognitive impairment, Parkinson's disease, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, stroke, multiple sclerosis, or history of significant head trauma with a reported loss of consciousness for greater than 30 minutes.
- Significant medical illnesses/conditions that is unstable and/or uncontrolled (lung or kidney disease, cancer).
- History of schizophrenia or bipolar disorder.
- Major Depression within the past year.
- History of alcohol or substance abuse or dependence within the past 2 years.
- Current use of Alzheimer's disease medications, including cholinesterase inhibitors and memantine.
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- Any unstable or severe cardiovascular disease or asthmatic condition.
- History of imaging confirmed transient ischemic attack or a score of >4 on the modified Hachinski ischemic scale.
- Significant abnormalities in laboratory blood tests that is considered to be a contraindication to exercise.
- Exclusion criteria specific to MR scanning (weight inappropriate for height, ferrous objects within the body, pregnancy, and a history of claustrophobia).
- A musculoskeletal issue (arthritis, osteoporosis, back problem) that would limit one's ability to engage in exercise
Trial locations and contacts
1 site in 1 country.
About this study
Official title: CYCLE-AD: Randomized Controlled Trial to Assess the Efficacy of Indoor Cycling in Slowing Disease Progression in Healthy Older Persons at Genetic Risk for Alzheimer's Disease
The overall goal of the CYCLE-AD trial is to determine the role of long-term, high intensity exercise in slowing or delaying the onset of cognitive and AD-related brain changes in e4 carriers. Successful translation and demonstration of the effectiveness of a scalable home-based exercise intervention capable of slowing or delaying disease onset will transform AD treatment, improve patient outcomes and quality of life, and reduce health care costs.
Read the detailed description
The apolipoprotein E epsilon 4 (APOE e4) allele is the most important genetic risk factor for late onset Alzheimer's disease (AD). A recent review by the World Health Organization highlighted the potential protective role of physical activity and exercise against cognitive decline, all-cause dementia, AD, and vascular dementia in healthy individuals. In an 18-month longitudinal observational study, investigators showed that sedentary e4 carriers experience significant declines in episodic memory and hippocampal volume compared to 4 carriers who engaged in moderate PA. Importantly, among 4 non-carriers, no significant longitudinal changes in cognition and brain imaging were observed whether the non-carriers were sedentary or engaged in moderate PA, suggesting that PA has a specific neuroprotective role in delaying the progression of AD in e4 carriers. Based on the results, a pragmatic, randomized controlled trial with blinded clinical and imaging outcomes is proposed to determine the impact of a home based, high intensity exercise intervention in healthy, cognitively intact e4 carriers between the ages of 65 and 80 years. The CYCLE-AD (CYcling to Cease or Limit the Effects of Alzheimer's Disease) trial will recruit otherwise healthy sedentary carriers randomized to one of two groups (n=75 each): 1) an Indoor Cycling (IC) group that participates in high-intensity interval training (HIIT; 60-90% of heart rate reserve) in their home via the commercially available Peloton® cycling system or 2) a Usual and Customary Care (UCC) group, in which participants engage in their habitual level of PA. Investigators hypothesize that an 18-month high-intensity aerobic exercise regimen will slow AD-related disease progression in sedentary elders at genetic risk for AD. Participants in the intervention group will engage in exercise 3x/week (minimum 90 minutes/week) for 18 months. Primary outcome measures, obtained at study entry and at 18 months, will include comprehensive cognitive testing and brain MR imaging to assess disease progression and a comprehensive PA/fitness assessment to measure the degree of change in physical fitness due to high intensity aerobic exercise.
- Being tested
- Indoor Cycling (IC)
- Keywords
- APOE ε4 allele, indoor cycling, exercise intervention, healthy elders, genetic risk for Alzheimer's Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Indoor Cycling (IC)Other
Participants will ride a Peloton bike 3x/week for 18 months.
| Study group | Role | What they receive |
|---|---|---|
| Indoor Cycling (IC) | Experimental | Participants will engage in high-intensity interval training (HIIT; 60-90% of heart rate reserve) in their home via the commercially available Peloton® cycling system or 2) 3x/week (minimum 90 minutes/week) for 18 months. Receives: Other: Indoor Cycling (IC) |
| Usual and Customary Care (UCC) | No intervention | Participants engage in their habitual level of physical activity. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rey Auditory Verbal Learning Test Total Recall Trials 1-5 (RAVLT1-5).
Determine the effects of an IC intervention on cognitive functioning
Measured: 18 months
Total Hippocampal Volume (THV)
Determine the effects of an IC intervention on MR brain imaging
Measured: 18 months
V̇O2max
Determine the effects of an IC intervention on PA/fitness testing
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2021
- Study start20 Oct 2021
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for High Intensity ExerciseStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A pragmatic, randomized controlled trial with blinded clinical and imaging outcomes
- Masking
- Triple blind
- Who is masked
- Care provider, Investigator, Outcomes assessor
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), University of Maryland, College Park, National Institute on Aging (NIA)
- Responsible party
- Principal investigator, Stephen Rao, The Cleveland Clinic
- Investigators
- Stephen Rao, PhD, Principal investigator, The Cleveland ClinicJay Alberts, PhD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04748861
- Sponsor's protocol ID
- IRB20-1198
- Other IDs
- 1R01AG070736-01
- Acronym
- CYCLE-AD
- Status last verified
- Aug 2026
- First submitted
- 3 Feb 2021
- Last updated
- 12 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CYCLE-AD: Randomized Controlled Trial to Assess the Efficacy of Indoor Cycling in Slowing Disease Progression in Healthy Older Persons at Genetic Risk for Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT04748861
- Acronym / sponsor ID
- CYCLE-AD / IRB20-1198
- Keywords
- APOE ε4 allele, indoor cycling, exercise intervention, healthy elders, genetic risk for Alzheimer's Disease
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 150 participants (actual)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), University of Maryland, College Park, National Institute on Aging (NIA)
- Study start
- 20 Oct 2021 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 10 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The overall goal of the CYCLE-AD trial is to determine the role of long-term, high intensity exercise in slowing or delaying the onset of cognitive and AD-related brain changes in e4 carriers. Successful translation and demonstration of the effectiveness of a scalable home-based exercise intervention capable of slowing or delaying disease onset will transform AD treatment, improve patient outcomes and quality of life, and reduce health care costs.
Detailed description
The apolipoprotein E epsilon 4 (APOE e4) allele is the most important genetic risk factor for late onset Alzheimer's disease (AD). A recent review by the World Health Organization highlighted the potential protective role of physical activity and exercise against cognitive decline, all-cause dementia, AD, and vascular dementia in healthy individuals. In an 18-month longitudinal observational study, investigators showed that sedentary e4 carriers experience significant declines in episodic memory and hippocampal volume compared to 4 carriers who engaged in moderate PA. Importantly, among 4 non-carriers, no significant longitudinal changes in cognition and brain imaging were observed whether the non-carriers were sedentary or engaged in moderate PA, suggesting that PA has a specific neuroprotective role in delaying the progression of AD in e4 carriers. Based on the results, a pragmatic, randomized controlled trial with blinded clinical and imaging outcomes is proposed to determine the impact of a home based, high intensity exercise intervention in healthy, cognitively intact e4 carriers between the ages of 65 and 80 years. The CYCLE-AD (CYcling to Cease or Limit the Effects of Alzheimer's Disease) trial will recruit otherwise healthy sedentary carriers randomized to one of two groups (n=75 each): 1) an Indoor Cycling (IC) group that participates in high-intensity interval training (HIIT; 60-90% of heart rate reserve) in their home via the commercially available Peloton® cycling system or 2) a Usual and Customary Care (UCC) group, in which participants engage in their habitual level of PA. Investigators hypothesize that an 18-month high-intensity aerobic exercise regimen will slow AD-related disease progression in sedentary elders at genetic risk for AD. Participants in the intervention group will engage in exercise 3x/week (minimum 90 minutes/week) for 18 months. Primary outcome measures, obtained at study entry and at 18 months, will include comprehensive cognitive testing and brain MR imaging to assess disease progression and a comprehensive PA/fitness assessment to measure the degree of change in physical fitness due to high intensity aerobic exercise.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- A pragmatic, randomized controlled trial with blinded clinical and imaging outcomes
| Arm | Type | Receives |
|---|---|---|
| Indoor Cycling (IC) | Experimental | Other: Indoor Cycling (IC)Participants will engage in high-intensity interval training (HIIT; 60-90% of heart rate reserve) in their home via the commercially available Peloton® cycling system or 2) 3x/week (minimum 90 minutes/week) for 18 months. |
| Usual and Customary Care (UCC) | No intervention | –Participants engage in their habitual level of physical activity. |
Who may qualify
- Ages
- 65 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (10 listed)
- Healthy elders, ages 65-80 years, inclusive
- No cognitive impairment based on screening examination
- APOE ε4 genotype
- Inactive; defined as exercising less than 3x per week at moderate-vigorous intensity
- Fluent in English (a requirement for neurocognitive testing)
Key exclusion criteria (11 listed)
- Any significant neurologic disease, including dementia, mild cognitive impairment, Parkinson's disease, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, stroke, multiple sclerosis, or history of significant head trauma with a reported loss of consciousness for greater than 30 minutes.
- Significant medical illnesses/conditions that is unstable and/or uncontrolled (lung or kidney disease, cancer).
- History of schizophrenia or bipolar disorder.
- Major Depression within the past year.
- History of alcohol or substance abuse or dependence within the past 2 years.
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 |
|---|---|---|
| Indoor Cycling (IC)Participants will ride a Peloton bike 3x/week for 18 months. | Other | Indoor Cycling (IC) |
Primary outcome
Rey Auditory Verbal Learning Test Total Recall Trials 1-5 (RAVLT1-5).
Time frame: 18 months
Determine the effects of an IC intervention on cognitive functioning
Total Hippocampal Volume (THV)
Time frame: 18 months
Determine the effects of an IC intervention on MR brain imaging
V̇O2max
Time frame: 18 months
Determine the effects of an IC intervention on PA/fitness testing
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2026.
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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.
Stephen Rao, PhD principal investigator
The Cleveland Clinic
Jay Alberts, PhD principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Indoor Cycling (IC) in people with High Intensity Exercise and Normal Cognition, run by The Cleveland Clinic 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 10 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: under way, not looking for participants, as of the sponsor's last update on 12 Aug 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?
This study is still under way. Results are not available in the source record yet.
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?
Rey Auditory Verbal Learning Test Total Recall Trials 1-5 (RAVLT1-5). (time frame: 18 months). The study lists 3 primary outcomes in all. 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 12 Aug 2026.