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Healthy AgingflADexNCT06584656

Understanding Cerebral Blood Flow Dynamics for Alzheimer's Disease Prevention Through Exercise

A study testing Aerobic exercise condition and Resistance exercise condition in people with Healthy Aging and Cognitive Function 1, Social, run by Universidad de Granada at 2 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Dementia is one of the leading causes of disability worldwide. Underlying biological mechanisms are crucial in preclinical stages of Alzheimer's disease (AD). Alterations in cerebral blood flow (CBF) and their relationship with AD blood-based biomarkers may be fundamental at early stages of the pathology. Read more about this study

Who is it for?
Ages 68 to 83 yearsHealthy volunteers can take part
What is being tested?
Aerobic exercise condition and Resistance exercise condition
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
2 sitesSpain
Study dates
25 Sep 2024to 2 Jan 2025
Phase
Interventional
Are there results?
None posted in the registry

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 68 to 83 years
  • All sexes
  • Healthy volunteers accepted
  • Older adult

Who may be able to join

  • Older adults
  • Aged 68-83 years
  • Non-pathological cerebral beta-amyloid status (based on Centiloid cut-point <12 measured by PET-CT)
  • APOEe4 negative status
  • Willingness to participate in exercise interventions

Who cannot join

  • Pathological diagnosis related to physical or mental condition
  • No living in community settings during the study
  • MRI incompatibility
  • Ambulatory with pain or regular use of an assisted walking device
  • Severe cardiovascular or respiratory conditions
  • Participation in another clinical trial within the last 30 days

Trial locations and contacts

2 sites in 1 country.

Spain2 sites

  • University of Granada

    Granada, Andalusia, 18016

  • Mind, Brain, and Behaviour Research Centre (CIMCYC, Centro de Investigación Mente, Cerebro y Comportamiento)

    Granada, 18011

Other trials in Spain

About this study

Official title: Understanding Cerebral Blood Flow Dynamics for Alzheimer's Disease Prevention Through Exercise: the flADex Study

Dementia is one of the leading causes of disability worldwide. Underlying biological mechanisms are crucial in preclinical stages of Alzheimer's disease (AD). Alterations in cerebral blood flow (CBF) and their relationship with AD blood-based biomarkers may be fundamental at early stages of the pathology. Physical exercise is a trigger to modify these biological mechanisms. Therefore, flADex aims to examine the acute effects of different types of exercise (resistance vs. aerobic vs. control) on CBF, AD blood-based biomarkers, and its cognitive implications in older adults. The hypothesis is that acute resistance or aerobic exercise will fluctuate levels of blood-based biomarkers, and will exert acute CBF changes combined with cognitive implications.

Read the detailed description

The aging population is at an increasing risk of developing Alzheimer's Disease (AD), which is characterized by cognitive decline and memory loss. Current pharmacological treatments have targeted amyloid-beta (Aβ) and tau protein, and have largely failed to halt or reverse the progression of AD. This has led to a growing interest on examining additional underlying mechanisms responsible for the initiation of AD pathology in this preclinical stage, such as cerebral blood flow (CBF) alterations or peripheral levels of AD blood-based biomarkers. Parallelly, exercise might act as a trigger for these potential underlying mechanisms of AD in older adults. Thus, this study seeks to explore the acute effects of different type of exercise on CBF, blood-based biomarkers, and its cognitive implications in older adults.

FlADex is a counterbalanced crossover trial that will include 20 adults aged 68 to 83 with non-pathological brain amyloid status (<12 centiloid) and APOE e4 noncarriers. Each participant will be included in all study conditions in a randomized order: (i) moderate aerobic exercise (between 60-70 of the Maximal Heart Rate (HRmax); (ii); resistance exercise (4-6 Moderate intensity of Rate of Perceived Exertion) and (iii) control resting condition. Each condition, lasting 30 minutes, will be performed once. CBF will be assessed by magnetic resonance imaging using pseudo-continuous arterial spin labeling at pre-condition and at 3 consecutive times post-condition (at 20', 27' and 34' min). Blood-based biomarkers (Aβ42, Aβ40, p-tau217, p-tau181, GFAP, NfL, BDNF, IGF-1) will be measured pre-condition and post-condition (at 0', 50', 70' min). Cognitive outcomes (Flanker Test and Picture Sequence Memory Test) and mood status (feeling scale and POMS questionnaire) will be measured pre and post condition.

FlADex trial will shed light on the acute effects of different types of exercises on CBF and AD blood-based biomarkers before beta-amyloid accumulation. We expect that aerobic and resistance exercise will have different effects on CBF dynamics and AD blood biomarker levels over time in older adults

Being tested
Aerobic exercise condition, Resistance exercise condition
Keywords
Alzheimer's Disease, Exercise, Cerebral Blood Flow, Biomarkers, Aging, Magnetic resonance imaging
Medical subject headings
Alzheimer Disease, Motor Activity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Aerobic exercise conditionBehavioural

    Aerobic session will last 30 min. The average intensity of the aerobic sessions will be 60-70% of the Maximal Heart Rate. Therefore, participant will perform a continuous moderate intensity aerobic bout of exercise on a cycle ergometer.

  • Resistance exercise conditionBehavioural

    Resistance exercise will last 30 min at 4-6 RPE (OMNI-Resistance Exercise Scale of Perceived Exertion from 0-10). The bout of resistance exercise will include a combination of upper and lower body exercises using elastic bands and the participants' body weight as the primary resistance. Eight different exercises will be performed per set, with 40 seconds per exercise, for a total of 3 sets. The exercises are based on basic movement patterns and include: glute bridge, front plank, standing face pull, incline push-up, squat, pallof press, walking lunge and seated shoulder press.

Study groups in NCT06584656
Study groupRoleWhat they receive
Aerobic exercise groupExperimental-Aerobic group. 30 min at 60-70% of the Maximal Heart Rate, moderate intensity on cycle.
Receives: Behavioral: Aerobic exercise condition
Resistance exercise groupExperimental30 min at 4-6 RPE (OMNI-Resistance Exercise Scale of Perceived Exertion), 3 sets of 8 exercise/set, 40 sec/exercise. Moderate intensity using elastic bands and body weight.
Receives: Behavioral: Resistance exercise condition
ControlNo intervention30 min seated watching a neutral documentary without cognitive engagement

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Cerebral Blood Flow (CBF)

    Specific acquisition parameters for Pseudo continuous Arterial Spin Labeling (pCASL) sequence are used to determinate global and regional CBF in resting condition. Structural T1 sequence (only pre-condition) is used to coregisted the pCASL and delineate regions of interest for CBF. Time-of-flight angiography (TOF) (before pCASL pre-condition and before first pCASL post-condition) sequence is used to identify the carotid arteries. The unit of measurement of the CBF is expressed as milliliters per 100 grams of brain tissue per minute (mL/100 g/min).

    Measured: 30 minutes before the experimental condition; and 20 minutes, 27 minutes and 34 minutes minutes after the experimental condition

Secondary outcomes (8)

  1. Change in Alzheimer disease blood-based biomarkers (Aβ42/40 ratio)

    The following biomarkers will be assessed: Amyloid-beta 42 (Aβ42), Amyloid-beta 40 (Aβ40). Aβ42 and Aβ40 will be combined to report Aβ42/40 ratio. Unit of measurement: Aβ42/40 is a ratio (no units) and represents the relative concentration of Aβ42 to Aβ40.

    Measured: 5 minutes before the experimental condition; and 0 minutes, 50 minutes and 70 minutes after the experimental condition

  2. Change in Alzheimer disease blood-based biomarkers (p-tau217, p-tau181, NfL and GFAP)

    The following biomarkers will be assessed: phosphorylated tau protein at positions 217 and 181 (p-tau217, p-tau181), Glial Fibrillary Acidic Protein (GFAP) and Neurofilament Light Chain (NfL). Unit of measurement: p-tau217, p-tau181, NfL and GFAP are commonly measured in picograms per milliliter (pg/mL).

    Measured: 5 minutes before the experimental condition; and 0 minutes, 50 minutes and 70 minutes after the experimental condition

  3. Change in growth factors (BDNF)

    Brain-Derived Neurotrophic Factor (BDNF) will be measured. Unit of measurement: BDNF is commonly measured in picograms per milliliter (pg/mL).

    Measured: 5 minutes before the experimental condition; and 0 minutes, 50 minutes and 70 minutes after the experimental condition

  4. Change in growth factors (IGF-1)

    Insulin-Like Growth Factor 1 (IGF-1) will be measured. Unit of measurement: IGF-1 is commonly measured in nanograms per milliliter (ng/mL).

    Measured: 5 minutes before the experimental condition; and 0 minutes, 50 minutes and 70 minutes after the experimental condition

  5. Change in episodic memory

    Episodic memory will be assessed using the Picture Sequence Memory Test from the Cognitive NIH Toolbox. The Cognitive NIH Toolbox is a computer-based battery which is available in Spanish. The Picture Sequence Memory Test measures episodic memory by deriving the participant's score from the cumulative number of adjacent pairs of pictures remembered correctly over two learning trials. The variable used for the for the PSMT is the theta score: The number of adjacent pairs placed correctly for each of trials 1 and 2 is converted to a theta score. This is a representation of the given participant estimated ability in the task.

    Measured: 15 minutes before the experimental condition; and 60 minutes after the experimental condition

  6. Change in inhibition/attention

    The Flanker task measures inhibitory control and attention by using the inverse efficiency score of incongruent trials. The inverse efficiency score is calculated as reaction time/accuracy (RT/ACC).

    Measured: 15 minutes before the experimental condition; and 60 minutes after the experimental condition

  7. Mood status

    Mood status will be evaluated using the validated scale Profile of Mood States (POMS). The POMS scale is a psychological assessment tool used to measure and evaluate a person's mood states. It consists of a questionnaire with a list of 15 adjectives or mood descriptors, where individuals rate how they have been feeling on a scale typically ranging from "Not at all" to "Extremely". We use an abbreviated version of the scale with 15 ítems. The ítems are divided into 5 dimensions: depression, vigour, anger, tension and fatigue. The final score is: ([depression]+[anger]+[tension]+[fatigue]) - [vigour].

    Measured: POMS will be measured 60 minutes before the experimental condition; and 70 minutes after the experimental condition

  8. Feeling scale

    Emotional response will be evaluated using the feeling scale (FS). The FS is an 11-point scale ranging from -5 (very bad) to +5 (very good) used to measure an individual's emotional feeling in terms of pleasure or displeasure at a specific moment.

    Measured: Feeling scale will be measured 1 minute before the experimental condition; and 1 minute after the experimental condition

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Sep 2024
  2. Study start25 Sep 2024
  3. Primary completion2 Jan 2025
  4. Study completion2 Jan 2025

Resources

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
Crossover
Masking
Double blind
Who is masked
Investigator, Outcomes assessor
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06584656
Sponsor's protocol ID
PID2022-137399OB-I0
Acronym
flADex
Status last verified
Mar 2025
First submitted
6 Aug 2024
Last updated
25 Mar 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: The protocol, statistical analyses plan and data management plan will be sharing open access. Data files including IPD, and corresponding data dictionaries, will be shared under restricted access and upon reasonable request (contact Irene Esteban-Cornejo) due to privacy issue and GDPR regulations. In principle, all collected IPD will be available for sharing under the \&#34;as open as possible, as closed as necessary\&#34; principle. The shared data files will be pseudonymized, only include participants who provided informed consent for sharing, and sharing is only possible when the data is used for research purposes regarding exercise, and brain health. This is stated at the informed consent files that the participants signed when they agree to participate.

Publications

  • Martin-Fuentes I, Fernandez-Gamez B, Vidal-Almela S, Caro-Rus A, Solis-Urra P, Sanchez-Aranda L, Fernandez-Ortega J, Sanchez-Martinez J, Coca-Pulido A, Olvera-Rojas M, Barranco-Moreno EJ, Marin-Alvarez JD, Bakker EA, Toval A, Bellon D, Sclafani A, Karikari TK, Erickson KI, Gomez-Rio M, Ortega FB, Esteban-Cornejo I. Understanding Cerebral Blood Flow Dynamics for Alzheimer's Disease Prevention Through Acute Exercise (flADex): Protocol for a Randomized Crossover Trial. Brain Behav. 2025 Nov;15(11):e70636. doi: 10.1002/brb3.70636.

    PubMed 41172131

Questions about this trial

What is this clinical trial studying?

A study testing Aerobic exercise condition and Resistance exercise condition in people with Healthy Aging and Cognitive Function 1, Social, run by Universidad de Granada at 2 sites in Spain.

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 5 inclusion and 6 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 25 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Spain. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 Cerebral Blood Flow (CBF) (time frame: 30 minutes before the experimental condition; and 20 minutes, 27 minutes and 34 minutes minutes after the experimental condition). 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 NCT06584656, which also lists 1 linked publication.

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 25 Mar 2025.

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