Alzheimer's Dementia (AD)AD-GUT-EXNCT07918417
Exercise in Alzheimer's Disease: Functional Biomarkers
A study testing High load, Moderate load and Healthy adults - High load in people with Alzheimer's Dementia (AD) and Alzheimer Disease (AD), run by European University Miguel de Cervantes at 1 site in Spain.
Trial summary
Alzheimer's disease (AD) is the leading cause of dementia worldwide and involves systemic alterations beyond the brain, such as loss of muscle strength, chronic low-grade inflammation, and gut microbiome dysbiosis. Read more about this study
- Who is it for?
- Ages 60 years and olderHealthy volunteers can take part
- Conditions the study is for
- Alzheimer's Dementia (AD), Alzheimer Disease (AD)
- What is being tested?
- High load, Moderate load and Healthy adults - High load
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteSpain
- Study dates
- 10 Nov 2026to 1 Dec 2027
- 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 60 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age ≥ 60 years
- Medical diagnosis of mild or moderate Alzheimer's disease based on clinical criteria and plasma biomarkers.
- Able to perform physical activity according to medical assessment
- Written informed consent from the participant or, when capacity is insufficient, from the legal representative
- Age ≥ 60 years
- No medical diagnosis of Alzheimer's disease or cognitive impairment according to clinical criteria
Show all 9Show fewer
- Preserved functional autonomy
- Able to perform physical activity according to medical assessment
- Written informed consent
Who cannot join
- Major surgery in the previous 3 months
- Total functional dependence
- Uncontrolled neuromuscular disease or severe heart disease
- Antibiotic, probiotic or corticosteroid treatment in the 4 weeks before biological sample collection
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Fabrzio Evangelista, Nurse contact
Spain1 site
Miguel de Cervantes European University
Valladolid, Valladolid, 47012
Francisco Javier Gutiérrez Pecharrómán, +34 983 001 000 ext. 22293, dit@uemc.es
Alejandro Santos Lozano, PhD
About this study
Official title: Physical Exercise in Alzheimer's Disease: Impact on Functional Biomarkers and the Muscle-Gut-Brain Axis
Alzheimer's disease (AD) is the leading cause of dementia worldwide and involves systemic alterations beyond the brain, such as loss of muscle strength, chronic low-grade inflammation, and gut microbiome dysbiosis. Physical exercise is a promising non-pharmacological therapy, and velocity-based resistance training has proven safe and effective in older adults. However, the effects of performing resistance exercises at high versus moderate velocity in people with AD remain unknown, and human evidence on how exercise modulates the gut microbiome in AD is very limited. This study aims to assess and compare the effects of two velocity-based resistance training modalities (high load at moderate velocity and moderate load at high velocity) versus usual care on the gut microbiome, systemic inflammation, plasma biomarkers, biological age, and intrinsic capacity in older adults with mild-to-moderate AD, using cognitively healthy older adults as a reference group.
Read the detailed description
Alzheimer's disease (AD) is the leading cause of dementia worldwide, affecting more than 50 million people, a figure projected to exceed 150 million by 2050, with a high economic and social burden that increases with disease severity. Beyond the accumulation of amyloid-β and hyperphosphorylated tau in the brain, AD involves systemic alterations even in early stages, including the progressive loss of muscle mass and strength (sarcopenia), chronic low-grade inflammation and disruption of the gut-brain axis. In this context, physical exercise has emerged as a high-impact adjuvant therapy capable of inducing relevant neurobiological and systemic adaptations. Among the available training modalities, velocity-based resistance training (i.e., controlling the execution velocity of each repetition to individualize the training load) has been shown to be safe and effective in older adults. However, the effects of executing resistance exercises at high velocity with moderate loads (e.g., 40-60% of one-repetition maximum [1RM]) versus moderate velocity with high loads (e.g., 60-80% 1RM) remain unexplored in people with AD. These exercise-induced adaptations can be monitored through circulating biomarkers that capture different biological responses: brain-derived neurotrophic factor (BDNF), a key mediator of neuronal survival and synaptic plasticity; the testosterone/cortisol ratio, an indicator of anabolic-catabolic balance; phosphorylated tau 217 (p-tau217), one of the most specific plasma markers of AD pathology; and Klotho, a protein linked to healthy aging with neuroprotective and anti-inflammatory functions. In parallel, the gut microbiome has gained prominence as a key modulator of the muscle-gut-brain axis. People with AD show reduced microbial diversity, an expansion of pro-inflammatory species and a reduction of short-chain fatty acid-producing bacteria, which compromise intestinal and blood-brain barrier integrity and amplify systemic inflammation. Although animal models consistently show that exercise promotes beneficial taxa and is associated with cognitive improvements, human studies have focused mainly on healthy older adults, and evidence in people diagnosed with AD is very limited. Moreover, molecular changes should translate into clinically relevant benefits. The World Health Organization's intrinsic capacity framework (cognition, locomotion, vitality, psychological and sensory domains) offers an integrative approach linking biological mechanisms with functional outcomes, together with sarcopenia, frailty, functional independence and caregiver burden. Therefore, this randomized controlled trial will compare two velocity-based resistance training modalities with usual care in older adults with mild-to-moderate AD, including a cognitively healthy reference group, to determine which modality has the greatest impact on the muscle-gut-brain axis, biological aging and intrinsic capacity, and whether these effects persist after detraining.
- Conditions
- Alzheimer's Dementia (AD), Alzheimer Disease (AD)
- Being tested
- High load, Moderate load, Healthy adults - High load, Healthy adults - Moderate load
- Keywords
- resistance training, Gut microbiome, Intrinsic capacity, Biological age
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High loadOther
Supervised resistance training programme lasting 12 weeks, with 3 sessions per week of 60 minutes each. Each session consists of a 15-minute mobility warm-up, in which one set of 10 repetitions with a load of 10% of body weight is performed for each exercise; a 35-minute main part with five exercises performed on guided resistance machines (leg press, leg extension, leg curl, chest press and seated row) in circuit format at 60-80% of one-repetition maximum (1RM); and a 10-minute cool-down with mobility and flexibility exercises. Training volume will be progressively increased throughout the programme by increasing the number of repetitions and sets per exercise.
Moderate loadOther
Supervised resistance training programme lasting 12 weeks, with 3 sessions per week of 60 minutes each. Each session consists of a 15-minute mobility warm-up, in which one set of 10 repetitions with a load of 10% of body weight is performed for each exercise; a 35-minute main part with five exercises performed on guided resistance machines (leg press, leg extension, leg curl, chest press and seated row) in circuit format at 40-60% of one-repetition maximum (1RM); and a 10-minute cool-down with mobility and flexibility exercises. Training volume will be progressively increased throughout the programme by increasing the number of repetitions and sets per exercise.
Healthy adults - High loadOther
One acute session of 60 minutes each. The session consists of a 15-minute mobility warm-up, in which one set of 10 repetitions with a load of 10% of body weight is performed for each exercise; a 35-minute main part with five exercises performed on guided resistance machines (leg press, leg extension, leg curl, chest press and seated row) in circuit format at 60% of one-repetition maximum (1RM); and a 10-minute cool-down with mobility and flexibility exercises.
Healthy adults - Moderate loadOther
One acute session of 60 minutes each. The session consists of a 15-minute mobility warm-up, in which one set of 10 repetitions with a load of 10% of body weight is performed for each exercise; a 35-minute main part with five exercises performed on guided resistance machines (leg press, leg extension, leg curl, chest press and seated row) in circuit format at 40% of one-repetition maximum (1RM); and a 10-minute cool-down with mobility and flexibility exercises.
| Study group | Role | What they receive |
|---|---|---|
| Alzheimer's disease - High load | Experimental | Participants with mild-to-moderate AD perform 12 weeks of supervised based resistance training at 60-80% 1RM, 3 sessions/week, plus usual care. Followed by 12 weeks of detraining. Receives: Other: High load |
| Alzheimer's disease - Moderate load | Experimental | Participants with mild-to-moderate AD perform 12 weeks of supervised based resistance training at 40-60% 1RM, 3 sessions/week, plus usual care. Followed by 12 weeks of detraining. Receives: Other: Moderate load |
| Alzheimer's disease - Usual care | No intervention | Participants with mild-to-moderate AD continue their usual care only (cognitive therapy, music therapy or other routine therapies). |
| Healthy reference group | Other | Cognitively healthy adults aged ≥ 60 years, not randomized for the longitudinal phase and not undergoing structured exercise. At week 1 they will be randomized to a single high-load session, a single moderate-load session or no exercise for the acute sub-study. Receives: Other: Healthy adults - High load; Other: Healthy adults - Moderate load |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gut microbiome
Participants will collect a stool sample at home using a commercial collection kit (REAL Stool Sample Collection Microbiome kit, Durviz S.L., Valencia, Spain). Samples will be divided into three aliquots and stored at -80ºC within 2 hours of collection. Microbial DNA will be extracted and the gut microbiome will be analysed by next-generation sequencing of the 16S rRNA gene.
Measured: Baseline, week 12 of intervention
Inflammation indices - Systemic Inflammation Response Index
Fasting venous blood samples will be collected by a qualified nurse from the antecubital vein and complete blood count will be assessed by flow cytometry to assess the Systemic Inflammation Response Index (SIRI) .
SIRI = (neutrophils × monocytes) / lymphocytes
All cell counts will be expressed as ×10⁹ cells/L or equivalent.
Measured: Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Plasma biomarkers - Brain-derived neurotrophic factor
Plasma concentrations of Brain-derived neutrophic factor (BDNF) will be measured by Enzyme-Linked ImmunoSorbent Assay (ELISA). Fasting venous blood samples will be collected by a qualified nurse from the antecubital vein into EDTA-treated vacutainers and centrifuged at 1500g for 10 minutes. Plasma will then undergo a second centrifugation at 2500g for 15 minutes and be stored in cryogenic vials at -80ºC. Results will be expressed in pg/mL or ng/mL.
Measured: Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Inflammation indices - Aggregate Index of Systemic Inflammation
Fasting venous blood samples will be collected by a qualified nurse from the antecubital vein and complete blood count will be assessed by flow cytometry to assess the Aggregate Index of Systemic Inflammation (AISI).
AISI = (neutrophils × monocytes × platelets) / lymphocytes
All cell counts will be expressed as ×10⁹ cells/L or equivalent.
Measured: Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Plasma biomarkers - p-tau217
Plasma concentrations of p-tau217 will be measured by ELISA. Fasting venous blood samples will be collected by a qualified nurse from the antecubital vein into EDTA-treated vacutainers and centrifuged at 1500g for 10 minutes. Plasma will then undergo a second centrifugation at 2500g for 15 minutes and be stored in cryogenic vials at -80ºC. Results will be expressed in pg/mL or ng/mL.
Measured: Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Plasma biomarkers - Klotho
Plasma concentrations of klotho will be measured by ELISA. Fasting venous blood samples will be collected by a qualified nurse from the antecubital vein into EDTA-treated vacutainers and centrifuged at 1500g for 10 minutes. Plasma will then undergo a second centrifugation at 2500g for 15 minutes and be stored in cryogenic vials at -80ºC. Results will be expressed in pg/mL or ng/mL.
Measured: Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Plasma biomarkers - Testosterone/cortisol ratio
Plasma ratio of testosterone/cortisol will be assessed by ELISA. Fasting venous blood samples will be collected by a qualified nurse from the antecubital vein into EDTA-treated vacutainers and centrifuged at 1500g for 10 minutes. Plasma will then undergo a second centrifugation at 2500g for 15 minutes and be stored in cryogenic vials at -80ºC. Results will be expressed in pg/mL or ng/mL.
Measured: Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Biological age
Fasting venous blood samples will be collected by a qualified nurse from the antecubital vein and analysed at the Hospital Universitario Río Hortega laboratory. PhenoAge clock based on crhonological age and nine blood biomarkers: albumin, creatinine, glucose, C-reactive protein, lymphocyte %, mean corpuscular volume, red blood cell distribution width, alkaline phosphatase and white blood count).
PhenoAge acceleration (years) will be computed as the residual from regression PhenoAge on chronological age.
Measured: Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Secondary outcomes (22)
Intrinsic capacity - Cognition
Cognition will be measured by Mini-Mental State Examination (0-35 points).
Measured: Baseline, week 1 of intervention (only verbal fluency), week 12 of intervention and week 12 of detraining
Intrinsic capacity - Cognition
Cognition will also be measured by Clock Drawing Test (0-10 points)
Measured: Baseline, week 1 of intervention (only verbal fluency), week 12 of intervention and week 12 of detraining
Intrinsic capacity - Cognition
Cognition will also be measured verbal fluency (words/min).
Measured: Baseline, week 1 of intervention (only verbal fluency), week 12 of intervention and week 12 of detraining
Intrinsic capacity - Locomotion
Locomotion will be assessed using the Short Physical Performance Battery (0-12 points).
Measured: Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Locomotion
Locomotion will be also assessed using the sit-to-stand muscle power (W) measured by PowerFrail app.
Measured: Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Vitality
Vitality will be measured by Mini-Nutritional Assessment (0-30 points).
Measured: Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Vitality
Vitality will also be measured by peak expiratory peak flow (L/min).
Measured: Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Vitality
Vitality will also be measured by handgrip strength (kg).
Measured: Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Psychological
Psychological domain will be assessed using the Cornell Scale for Depression in Dementia (0-38 points).
Measured: Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Psychological
Psychological domain will also be assessed using the Geriatric Depression Scale-10 (0-10 points).
Measured: Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Psychological
Psychological domain will also be assessed using the Neuropsychiatric inventory.
Measured: Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Sensory capacity
Sensory domain will be assessed by self-, clinician- or caregiver-reported vision and hearing problems
Measured: Baseline, week 12 of intervention and week 12 of detraining
Quadriceps muscle thickness
Rectus femoris and vastus lateralis thickness (cm) will be measured with a real-time B-mode ultrasound (MyLab Gamma, Esaote, Genoa, Italy) and a linear transducer (SL 1543, 3-13 MHz; Esaote)
Measured: Baseline, week 12 of intervention and week 12 of detraining
Functional outcomes - Functional capacity
Functional capacity will be assessed using the 6-Minute walking test (6MWT). Participants will walk along a 30-metre corridor marked every 10 metres to cover the maximum distance possible in six minutes. Total distance will be recorded (in meters). r.
Measured: Baseline, week 12 of intervention and week 12 of detraining
Functional outcomes - Functional independence in basic activities of daily living
The Barthel Index assesses ten basic activities of daily living. The score ranges from 0 to 100 points, with higher scores indicating greater independence: total dependence (0-20), severe (21-60), moderate (61-90), mild dependence (91-99) and independence (100).
Measured: Baseline, week 12 of intervention and week 12 of detraining
Functional outcomes - Heart rate recovery
Additionally to the distance, heart rate recovery (bpm) will be calculated as the difference between heart rate at the end of the test (6MWT) and one minute after
Measured: Baseline, week 12 of intervention and week 12 of detraining
Functional outcomes - Functional independence in instrumental activities of daily living
The Lawton and Brody Scale evaluates eight instrumental activities of daily living. The score ranges from 0 to 8 points, with lower scores indicating greater dependence.
Measured: Baseline, week 12 of intervention and week 12 of detraining
Clinical outcomes - Bioimpedance
The NUTRILAB bioimpedance device (AKERN Srl, Florence, Italy) will be used. This non-invasive method measures the body's resistance and reactance of the body to the passage of a low-intensity electric current and enables the determination of various body parameters. Bioimpedance provides accurate data on body fat percentage, muscle mass, total body water and other relevant indicators such as phase angle and Z-score. Users will be instructed to remove all metal-containing objects and remain in a supine position on a couch during the measurements, with the legs in 45° abduction, the shoulders in 30° abduction relative to the center of the body and the hands in pronation. After cleaning the skin with alcohol, two adhesive electrodes (Biatrodes Akern Srl, Florence, Italy) will be placed on the surface of the right hand and two on the right foot.
The measurement results will be given in different unit measures depending on the specific variable assessed
Measured: Baseline, week 12 of intervention and week 12 of detraining
Clinical outcomes - Risk of sarcopenia
Sarcopenia will be assessed following the European Working Group on Sarcopenia in Older People (EWGSOP2) algorithm.
Measured: Baseline, week 12 of intervention and week 12 of detraining
Clinical outcomes - Comorbidities
Comorbidities will be recorded through the Charlson Comorbidity Index. Score is given in points, ith higher scores indicating greater comorbidity burden.
Measured: Baseline, week 12 of intervention and week 12 of detraining
Pyschosocial outcomes - Caregiver burden
Caregiver burden will be assessed by the Zarit Burden Interview. It consists of 22 items on the caregiver's psychosocial, economic and emotional well-being. The score ranges from 0 to 88 points, with higher scores indicating greater caregiver burden.
Measured: Baseline, week 12 of intervention and week 12 of detraining
Pyschosocial outcomes - Socio-familial situation
The Gijón Socio-Familial Assessment will be used. It evaluates five dimensions: personal situation, economic situation, housing, social relationships and support from the social network. The score ranges from 5 to 25 points, with higher scores indicating greater social risk (15 or more indicates a social problem).
Measured: Baseline, week 12 of intervention and week 12 of detraining
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2026
- Study start10 Nov 2026 (estimated)
- Primary completion31 Oct 2027 (estimated)
- Study completion1 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer's Dementia (AD)Studies 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
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Three randomized parallel arms of participants with mild-to-moderate AD plus a non-randomized cognitively healthy reference group (healthy participants will be randomized to one of three conditions only for the week-1 acute session).
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- European University Miguel de Cervantes
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Rio Hortega
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07918417
- Sponsor's protocol ID
- PI-DOC013-ADD-GUT-EXERCISE
- Acronym
- AD-GUT-EX
- Status last verified
- Oct 2026
- First submitted
- 26 Oct 2026
- Last updated
- 5 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Physical Exercise in Alzheimer's Disease: Impact on Functional Biomarkers and the Muscle-Gut-Brain Axis
- ClinicalTrials.gov ID
- NCT07918417
- Acronym / sponsor ID
- AD-GUT-EX / PI-DOC013-ADD-GUT-EXERCISE
- Conditions
- Alzheimer's Dementia (AD), Alzheimer Disease (AD)
- Keywords
- resistance training, Gut microbiome, Intrinsic capacity, Biological age
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- European University Miguel de CervantesUniversity, hospital or other
- Collaborators
- Hospital Rio Hortega
- Study start
- 10 Nov 2026 (estimated)
- Primary completion
- 31 Oct 2027 (estimated)
- Study completion
- 1 Dec 2027 (estimated)
- First posted
- 5 Nov 2026 (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.
Alzheimer's disease (AD) is the leading cause of dementia worldwide and involves systemic alterations beyond the brain, such as loss of muscle strength, chronic low-grade inflammation, and gut microbiome dysbiosis. Physical exercise is a promising non-pharmacological therapy, and velocity-based resistance training has proven safe and effective in older adults. However, the effects of performing resistance exercises at high versus moderate velocity in people with AD remain unknown, and human evidence on how exercise modulates the gut microbiome in AD is very limited. This study aims to assess and compare the effects of two velocity-based resistance training modalities (high load at moderate velocity and moderate load at high velocity) versus usual care on the gut microbiome, systemic inflammation, plasma biomarkers, biological age, and intrinsic capacity in older adults with mild-to-moderate AD, using cognitively healthy older adults as a reference group.
Detailed description
Alzheimer's disease (AD) is the leading cause of dementia worldwide, affecting more than 50 million people, a figure projected to exceed 150 million by 2050, with a high economic and social burden that increases with disease severity. Beyond the accumulation of amyloid-β and hyperphosphorylated tau in the brain, AD involves systemic alterations even in early stages, including the progressive loss of muscle mass and strength (sarcopenia), chronic low-grade inflammation and disruption of the gut-brain axis. In this context, physical exercise has emerged as a high-impact adjuvant therapy capable of inducing relevant neurobiological and systemic adaptations. Among the available training modalities, velocity-based resistance training (i.e., controlling the execution velocity of each repetition to individualize the training load) has been shown to be safe and effective in older adults. However, the effects of executing resistance exercises at high velocity with moderate loads (e.g., 40-60% of one-repetition maximum [1RM]) versus moderate velocity with high loads (e.g., 60-80% 1RM) remain unexplored in people with AD. These exercise-induced adaptations can be monitored through circulating biomarkers that capture different biological responses: brain-derived neurotrophic factor (BDNF), a key mediator of neuronal survival and synaptic plasticity; the testosterone/cortisol ratio, an indicator of anabolic-catabolic balance; phosphorylated tau 217 (p-tau217), one of the most specific plasma markers of AD pathology; and Klotho, a protein linked to healthy aging with neuroprotective and anti-inflammatory functions. In parallel, the gut microbiome has gained prominence as a key modulator of the muscle-gut-brain axis. People with AD show reduced microbial diversity, an expansion of pro-inflammatory species and a reduction of short-chain fatty acid-producing bacteria, which compromise intestinal and blood-brain barrier integrity and amplify systemic inflammation. Although animal models consistently show that exercise promotes beneficial taxa and is associated with cognitive improvements, human studies have focused mainly on healthy older adults, and evidence in people diagnosed with AD is very limited. Moreover, molecular changes should translate into clinically relevant benefits. The World Health Organization's intrinsic capacity framework (cognition, locomotion, vitality, psychological and sensory domains) offers an integrative approach linking biological mechanisms with functional outcomes, together with sarcopenia, frailty, functional independence and caregiver burden. Therefore, this randomized controlled trial will compare two velocity-based resistance training modalities with usual care in older adults with mild-to-moderate AD, including a cognitively healthy reference group, to determine which modality has the greatest impact on the muscle-gut-brain axis, biological aging and intrinsic capacity, and whether these effects persist after detraining.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
- Model description
- Three randomized parallel arms of participants with mild-to-moderate AD plus a non-randomized cognitively healthy reference group (healthy participants will be randomized to one of three conditions only for the week-1 acute session).
| Arm | Type | Receives |
|---|---|---|
| Alzheimer's disease - High load | Experimental | Other: High loadParticipants with mild-to-moderate AD perform 12 weeks of supervised based resistance training at 60-80% 1RM, 3 sessions/week, plus usual care. Followed by 12 weeks of detraining. |
| Alzheimer's disease - Moderate load | Experimental | Other: Moderate loadParticipants with mild-to-moderate AD perform 12 weeks of supervised based resistance training at 40-60% 1RM, 3 sessions/week, plus usual care. Followed by 12 weeks of detraining. |
| Alzheimer's disease - Usual care | No intervention | –Participants with mild-to-moderate AD continue their usual care only (cognitive therapy, music therapy or other routine therapies). |
| Healthy reference group | Other | Other: Healthy adults - High load, Other: Healthy adults - Moderate loadCognitively healthy adults aged ≥ 60 years, not randomized for the longitudinal phase and not undergoing structured exercise. At week 1 they will be randomized to a single high-load session, a single moderate-load session or no exercise for the acute sub-study. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age ≥ 60 years
- Medical diagnosis of mild or moderate Alzheimer's disease based on clinical criteria and plasma biomarkers.
- Able to perform physical activity according to medical assessment
- Written informed consent from the participant or, when capacity is insufficient, from the legal representative
- Age ≥ 60 years
Key exclusion criteria (4 listed)
- Major surgery in the previous 3 months
- Total functional dependence
- Uncontrolled neuromuscular disease or severe heart disease
- Antibiotic, probiotic or corticosteroid treatment in the 4 weeks before biological sample collection
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 |
|---|---|---|
| High loadSupervised resistance training programme lasting 12 weeks, with 3 sessions per week of 60 minutes each. Each session consists of a 15-minute mobility warm-up, in which one set of 10 repetitions with a load of 10% of body weight is performed for each exercise; a 35-minute main part with five exercises performed on guided resistance machines (leg press, leg extension, leg curl, chest press and seated row) in circuit format at 60-80% of one-repetition maximum (1RM); and a 10-minute cool-down with mobility and flexibility exercises. Training volume will be progressively increased throughout the programme by increasing the number of repetitions and sets per exercise. | Other | Alzheimer's disease - High load |
| Moderate loadSupervised resistance training programme lasting 12 weeks, with 3 sessions per week of 60 minutes each. Each session consists of a 15-minute mobility warm-up, in which one set of 10 repetitions with a load of 10% of body weight is performed for each exercise; a 35-minute main part with five exercises performed on guided resistance machines (leg press, leg extension, leg curl, chest press and seated row) in circuit format at 40-60% of one-repetition maximum (1RM); and a 10-minute cool-down with mobility and flexibility exercises. Training volume will be progressively increased throughout the programme by increasing the number of repetitions and sets per exercise. | Other | Alzheimer's disease - Moderate load |
| Healthy adults - High loadOne acute session of 60 minutes each. The session consists of a 15-minute mobility warm-up, in which one set of 10 repetitions with a load of 10% of body weight is performed for each exercise; a 35-minute main part with five exercises performed on guided resistance machines (leg press, leg extension, leg curl, chest press and seated row) in circuit format at 60% of one-repetition maximum (1RM); and a 10-minute cool-down with mobility and flexibility exercises. | Other | Healthy reference group |
| Healthy adults - Moderate loadOne acute session of 60 minutes each. The session consists of a 15-minute mobility warm-up, in which one set of 10 repetitions with a load of 10% of body weight is performed for each exercise; a 35-minute main part with five exercises performed on guided resistance machines (leg press, leg extension, leg curl, chest press and seated row) in circuit format at 40% of one-repetition maximum (1RM); and a 10-minute cool-down with mobility and flexibility exercises. | Other | Healthy reference group |
Primary outcome
Gut microbiome
Time frame: Baseline, week 12 of intervention
Participants will collect a stool sample at home using a commercial collection kit (REAL Stool Sample Collection Microbiome kit, Durviz S.L., Valencia, Spain). Samples will be divided into three aliquots and stored at -80ºC within 2 hours of collection. Microbial DNA will be extracted and the gut microbiome will be analysed by next-generation sequencing of the 16S rRNA gene.
Inflammation indices - Systemic Inflammation Response Index
Time frame: Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Fasting venous blood samples will be collected by a qualified nurse from the antecubital vein and complete blood count will be assessed by flow cytometry to assess the Systemic Inflammation Response Index (SIRI) . SIRI = (neutrophils × monocytes) / lymphocytes All cell counts will be expressed as ×10⁹ cells/L or equivalent.
Plasma biomarkers - Brain-derived neurotrophic factor
Time frame: Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Plasma concentrations of Brain-derived neutrophic factor (BDNF) will be measured by Enzyme-Linked ImmunoSorbent Assay (ELISA). Fasting venous blood samples will be collected by a qualified nurse from the antecubital vein into EDTA-treated vacutainers and centrifuged at 1500g for 10 minutes. Plasma will then undergo a second centrifugation at 2500g for 15 minutes and be stored in cryogenic vials at -80ºC. Results will be expressed in pg/mL or ng/mL.
Inflammation indices - Aggregate Index of Systemic Inflammation
Time frame: Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Fasting venous blood samples will be collected by a qualified nurse from the antecubital vein and complete blood count will be assessed by flow cytometry to assess the Aggregate Index of Systemic Inflammation (AISI). AISI = (neutrophils × monocytes × platelets) / lymphocytes All cell counts will be expressed as ×10⁹ cells/L or equivalent.
Plasma biomarkers - p-tau217
Time frame: Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Plasma concentrations of p-tau217 will be measured by ELISA. Fasting venous blood samples will be collected by a qualified nurse from the antecubital vein into EDTA-treated vacutainers and centrifuged at 1500g for 10 minutes. Plasma will then undergo a second centrifugation at 2500g for 15 minutes and be stored in cryogenic vials at -80ºC. Results will be expressed in pg/mL or ng/mL.
Plasma biomarkers - Klotho
Time frame: Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Plasma concentrations of klotho will be measured by ELISA. Fasting venous blood samples will be collected by a qualified nurse from the antecubital vein into EDTA-treated vacutainers and centrifuged at 1500g for 10 minutes. Plasma will then undergo a second centrifugation at 2500g for 15 minutes and be stored in cryogenic vials at -80ºC. Results will be expressed in pg/mL or ng/mL.
Plasma biomarkers - Testosterone/cortisol ratio
Time frame: Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Plasma ratio of testosterone/cortisol will be assessed by ELISA. Fasting venous blood samples will be collected by a qualified nurse from the antecubital vein into EDTA-treated vacutainers and centrifuged at 1500g for 10 minutes. Plasma will then undergo a second centrifugation at 2500g for 15 minutes and be stored in cryogenic vials at -80ºC. Results will be expressed in pg/mL or ng/mL.
Biological age
Time frame: Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Fasting venous blood samples will be collected by a qualified nurse from the antecubital vein and analysed at the Hospital Universitario Río Hortega laboratory. PhenoAge clock based on crhonological age and nine blood biomarkers: albumin, creatinine, glucose, C-reactive protein, lymphocyte %, mean corpuscular volume, red blood cell distribution width, alkaline phosphatase and white blood count). PhenoAge acceleration (years) will be computed as the residual from regression PhenoAge on chronological age.
22 secondary outcomes
Intrinsic capacity - Cognition
Time frame: Baseline, week 1 of intervention (only verbal fluency), week 12 of intervention and week 12 of detraining
Intrinsic capacity - Cognition
Time frame: Baseline, week 1 of intervention (only verbal fluency), week 12 of intervention and week 12 of detraining
Intrinsic capacity - Cognition
Time frame: Baseline, week 1 of intervention (only verbal fluency), week 12 of intervention and week 12 of detraining
Intrinsic capacity - Locomotion
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Locomotion
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Vitality
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Vitality
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Vitality
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Psychological
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Psychological
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Psychological
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Sensory capacity
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Quadriceps muscle thickness
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Functional outcomes - Functional capacity
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Functional outcomes - Functional independence in basic activities of daily living
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Functional outcomes - Heart rate recovery
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Functional outcomes - Functional independence in instrumental activities of daily living
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Clinical outcomes - Bioimpedance
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Clinical outcomes - Risk of sarcopenia
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Clinical outcomes - Comorbidities
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Pyschosocial outcomes - Caregiver burden
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Pyschosocial outcomes - Socio-familial situation
Time frame: Baseline, week 12 of intervention and week 12 of detraining
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 5 Nov 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.
Fabrzio Evangelista, Nurse contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High load, Moderate load and Healthy adults - High load in people with Alzheimer's Dementia (AD) and Alzheimer Disease (AD), run by European University Miguel de Cervantes at 1 site 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 9 inclusion and 4 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: opening soon, as of the sponsor's last update on 5 Nov 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 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?
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?
Contact Alejandro Santos-Lozano, PhD (+34983001000 ext. 22292, asantos@uemc.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gut microbiome (time frame: Baseline, week 12 of intervention). The study lists 8 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 5 Nov 2026.