MCINCT06746909
Identification of Neuroinflammation and Neuroimaging Biomarkers Through Data Driven Artificial Intelligence Techniques for Unraveling the Heterogeneity of Aged Subjects at Risk of Dementia and to Better Inform Prevention Strategies
A study testing Multidomain cognitive training and physical training in people with MCI and SCD, run by IRCCS Fondazione Stella Maris at 1 site in Italy.
Trial summary
SCD and MCI are very heterogeneous conditions, which can be prodromal to different types of dementia. The application of data driven clustering methods on neuroimaging and inflammatory data aims at identifying the features characterizing subgroups of subjects at high risk of developing overt dementia. Read more about this study
- Who is it for?
- Ages 65 to 89 yearsHealthy volunteers can take part
- What is being tested?
- Multidomain cognitive training and physical training
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 115 participants
- Where
- 1 siteItaly
- Study dates
- 1 Feb 2022to 30 Jun 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 89 years
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- age between 65 and 89 years; 5 years of schooling;
- diagnosis of Mild Cognitive Impairment (Croisile et al., 2011) or
- diagnosis of Subjective Cognitive Decline (Jessen et al., 2014).
Who cannot join
- neurological pathologies; dementia;
- psychiatric disorders;
- pathologies or orthopedic problems limiting participation to the aerobic physical training program and to the MR imaging.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Michela Tosetti, MSc contact
Italy1 site, 1 recruiting
- Recruiting
Azienda Ospedaliera Universitaria Pisana
Pisa, 56126
Valentina Nicoletti, MD, +39 050992443, valentina.nicoletti@ao-pisa.toscana.it
About this study
SCD and MCI are very heterogeneous conditions, which can be prodromal to different types of dementia. The application of data driven clustering methods on neuroimaging and inflammatory data aims at identifying the features characterizing subgroups of subjects at high risk of developing overt dementia. This approach promises to develop tailored early interventions for subjects with profiles of cognitive decline correlating with high risk of progression. To this end in this project, we propose to examine in these subjects both brain structure and cerebral blood flow (CBF) through MR T1-weighted and pCASL (pseudo-continuous arterial spin labeling) imaging and the neuroinflammatory status. The latter will be done by measuring the populations of innate and adaptive immune cells, the chemokines that are required to attract these cells to their potential sites of action in the CNS, and the cytokines by means they exert their function. The analyses performed in aged subjects with MCI and in SCD, will allow identifying common mechanisms predisposing to an increased susceptibility to progression to overt cognitive decline.
Read the detailed description
The recruitment will involve 35 MCI in the training cohort, 35 MCI in the placebo cohort and 75 SCD subjects.
Cognitive assessment: A comprehensive battery of neuropsychological tests will assess performance in memory, attention and executive function domains. For all MCI subjects the same cognitive assessment will be performed at the beginning of the study (T0), after 7 months (T7) and after 14 months (T14). SCD subjects will perform the cognitive assessment at T0, T7, T14 and after 28 months (T28), depending on the assigned arm.
Instrumental assessment: for all MCI subjects the instrumental assessment, MR brain scans (T1-weighted and pCASL), will be performed at T0 and at T7. 35 SCD subjects will be subjected to the instrumental assessment at T0 and at T28.
Blood samples: Blood samples for peripheral blood mononuclear cell (PBMC) isolation will be withdrawn from all MCI and SCD subjects, at baseline. For all MCI patients blood samples will be taken also at T7 and T14, for SCD subjects also at T28. Cellular mediators will be assessed by Flow cytometry analysis of monocyte/macrophage, T cell (CD3/CD4/CD8) and regulatory T cell (CD4+CD25+IL7Rlo). Serum/plasma will be prepared and stored for determination of soluble immune mediators of inflammation. ELISA determinations will be performed for IFNgamma, IL12, TNFalpha, IL-6, CCL2 and BDNF.
Intervention: After baseline assessment the MCI-training and SCD-training group will receive a 7 months-long multidomain training, including cognitive, physical exercise and music therapy; while, the MCI-no training and SCD no-training will be followed in their natural history. According to the TtB protocol (Train the Brain Consortium, 2017) enrolled subjects will be assigned to mixed-gender classes of maximum 10 subjects each and given 2 sessions of 60 minutes supervised cognitive training per day, 3 times a week, and one of 60 minutes supervised aerobic physical activity per day, 3 times a week for 7 month. The cognitive training programme will be based on 8 cycles composed by 18 sessions of exercises and activities aimed at stimulating multiple cognitive functions. Each cycle will last 3 weeks, after which the same kind of cognitive stimulation sessions will be restarted, with exercises and activities of increased complexity. Each cycle will be structured in sessions aimed at stimulating specific cognitive domains and in sessions focused on multimodal activities. The physical training will include aerobic exercise on an ergometer cycle, whose duration will be increased gradually from 10 to 20 minutes followed by exercises targeted to improve muscle strength, physical function, neuromuscular control and flexibility.
The MCI-training and MCI-no training groups will be compared at T7 in terms of cognitive performances, CBF, gray matter atrophy and inflammatory markers. An additional comparison in terms of cognitive integrity and inflammatory markers will be performed at T14. The SCD-training and SCD-no training groups will be compared at T7 in terms of cognitive performances and inflammatory markers. An additional comparison in terms of cognitive integrity and inflammatory markers will be performed at T14.
The MR acquisitions performed on MCI and SCD subjects at baseline (both T1-weighted and pCASL) will be processed in order to obtain measurements on brain structure volumes and CBF. On these measures a consensus clustering technique will be applied in order to identify homogeneous subgroups of anatomical and CBF patterns on both MCI and SCD cohort.
First, the MCI and SCD cohorts will be treated separately in order to detect subgroups of the different clinical categories.
Second, the MCI and SCD cohorts will be jointly treated in order to detect potential neuroimaging affinity in subjects who exhibit different cognitive impairments.
After the first evaluation with consensus clustering approach, novel clustering techniques such as clustering methods based on deep neural network (Xie et al. 2016) will be explored.
The robustness of clustering methodologies of neuroimaging data will be tested by a cross validation approach and by enriching the sample with anatomical and perfusion data publicly available thanks to the ADNI consortium (at the moment about 160 anatomical and CBF data are available for a cohort of MCI and SCD subjects).
- Being tested
- Multidomain cognitive training and physical training
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Multidomain cognitive training and physical trainingOther
The cognitive training programme will be based on 8 cycles composed by 18 sessions of exercises and activities aimed at stimulating multiple cognitive functions. Each cycle will last 3 weeks, after which the same kind of cognitive stimulation sessions will be restarted, with exercises and activities of increased complexity. Each cycle will be structured in sessions aimed at stimulating specific cognitive domains and in sessions focused on multimodal activities (music-therapy, cineforum, etc.).
The physical training will include aerobic exercise on an ergometer cycle, whose duration will be increased gradually from 10 to 20 minutes followed by exercises targeted to improve muscle strength, physical function, neuromuscular control and flexibility.
| Study group | Role | What they receive |
|---|---|---|
| MCI training | Active comparator | After baseline assessment the MCI-training group will receive a 7 months-long multidomain training, including cognitive, physical exercise and music therapy; Enrolled subjects will be assigned to mixed-gender classes of maximum 10 subjects each and given 2 sessions of 60 minutes supervised cognitive training per day, 3 times a week, and one of 60 minutes supervised aerobic physical activity per day, 3 times a week for 7 months. Receives: Other: Multidomain cognitive training and physical training |
| MCI no-training | No intervention | Follow up of natural history of subjects after 7 months |
| healthy subjects | No intervention | Follow up of natural history of subjects after 7 months |
| SCD | No intervention | Follow up of natural history of subjects after 28 months |
| SCD training | Active comparator | After baseline assessment the MCI-training group will receive a 7 months-long multidomain training, including cognitive, physical exercise and music therapy; Enrolled subjects will be assigned to mixed-gender classes of maximum 10 subjects each and given 2 sessions of 60 minutes supervised cognitive training per day, 3 times a week, and one of 60 minutes supervised aerobic physical activity per day, 3 times a week for 7 months. Receives: Other: Multidomain cognitive training and physical training |
| SCD no-training | No intervention | Follow up of natural history of subjects after 7 months |
What is being measured
The primary outcome is the main question the study is designed to answer.
Short term training effects
The MCI-training and MCI-no training, the SCD-training and SCD-no training groups will be compared at T7 in terms of cognitive performances, CBF, gray matter atrophy (both CBF and GM atrophy will be evaluated on different regions of interest) and inflammatory markers.
Measured: 7 months
Secondary outcomes (1)
Sample stratification
clustering technique will be applied in order to identify homogeneous subgroups of anatomical, CBF, neuroinflammation patterns on both MCI and SCD cohort. The exploratory hypothesis is that different clusters at baseline may have different clinical outcomes at T7, T14 and T28. The outcome can also be modulated by the multi-domain intervention.
Measured: 7, 14 and 28 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2024
- Study start1 Feb 2022
- Primary completion30 May 2025 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MCIStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 115 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS Fondazione Stella Maris
- Sponsor type
- University, hospital or other
- Collaborators
- Humanitas Research Hospital IRCCS, Rozzano-Milan, Azienda Ospedaliero, Universitaria Pisana, Istituto di Neuroscienze Consiglio Nazionale delle Ricerche
- Responsible party
- Principal investigator, Paolo Bosco, IRCCS Fondazione Stella Maris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06746909
- Sponsor's protocol ID
- GR-2019-12370776
- Other IDs
- GR-2019-12370776, "Age-It", PE00000015
- Status last verified
- Nov 2024
- First submitted
- 18 Dec 2024
- Last updated
- 24 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: GDPR compliance concerns
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification of Neuroinflammation and Neuroimaging Biomarkers Through Data Driven Artificial Intelligence Techniques for Unraveling the Heterogeneity of Aged Subjects at Risk of Dementia and to Better Inform Prevention Strategies
- ClinicalTrials.gov ID
- NCT06746909
- Acronym / sponsor ID
- GR-2019-12370776
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 115 participants (estimated)
- Lead sponsor
- IRCCS Fondazione Stella MarisUniversity, hospital or other
- Collaborators
- Humanitas Research Hospital IRCCS, Rozzano-Milan, Azienda Ospedaliero, Universitaria Pisana, Istituto di Neuroscienze Consiglio Nazionale delle Ricerche
- Study start
- 1 Feb 2022 (actual)
- Primary completion
- 30 May 2025 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 24 Dec 2024 (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.
SCD and MCI are very heterogeneous conditions, which can be prodromal to different types of dementia. The application of data driven clustering methods on neuroimaging and inflammatory data aims at identifying the features characterizing subgroups of subjects at high risk of developing overt dementia. This approach promises to develop tailored early interventions for subjects with profiles of cognitive decline correlating with high risk of progression. To this end in this project, we propose to examine in these subjects both brain structure and cerebral blood flow (CBF) through MR T1-weighted and pCASL (pseudo-continuous arterial spin labeling) imaging and the neuroinflammatory status. The latter will be done by measuring the populations of innate and adaptive immune cells, the chemokines that are required to attract these cells to their potential sites of action in the CNS, and the cytokines by means they exert their function. The analyses performed in aged subjects with MCI and in SCD, will allow identifying common mechanisms predisposing to an increased susceptibility to progression to overt cognitive decline.
Detailed description
The recruitment will involve 35 MCI in the training cohort, 35 MCI in the placebo cohort and 75 SCD subjects.
Cognitive assessment: A comprehensive battery of neuropsychological tests will assess performance in memory, attention and executive function domains. For all MCI subjects the same cognitive assessment will be performed at the beginning of the study (T0), after 7 months (T7) and after 14 months (T14). SCD subjects will perform the cognitive assessment at T0, T7, T14 and after 28 months (T28), depending on the assigned arm.
Instrumental assessment: for all MCI subjects the instrumental assessment, MR brain scans (T1-weighted and pCASL), will be performed at T0 and at T7. 35 SCD subjects will be subjected to the instrumental assessment at T0 and at T28.
Blood samples: Blood samples for peripheral blood mononuclear cell (PBMC) isolation will be withdrawn from all MCI and SCD subjects, at baseline. For all MCI patients blood samples will be taken also at T7 and T14, for SCD subjects also at T28. Cellular mediators will be assessed by Flow cytometry analysis of monocyte/macrophage, T cell (CD3/CD4/CD8) and regulatory T cell (CD4+CD25+IL7Rlo). Serum/plasma will be prepared and stored for determination of soluble immune mediators of inflammation. ELISA determinations will be performed for IFNgamma, IL12, TNFalpha, IL-6, CCL2 and BDNF.
Intervention: After baseline assessment the MCI-training and SCD-training group will receive a 7 months-long multidomain training, including cognitive, physical exercise and music therapy; while, the MCI-no training and SCD no-training will be followed in their natural history. According to the TtB protocol (Train the Brain Consortium, 2017) enrolled subjects will be assigned to mixed-gender classes of maximum 10 subjects each and given 2 sessions of 60 minutes supervised cognitive training per day, 3 times a week, and one of 60 minutes supervised aerobic physical activity per day, 3 times a week for 7 month. The cognitive training programme will be based on 8 cycles composed by 18 sessions of exercises and activities aimed at stimulating multiple cognitive functions. Each cycle will last 3 weeks, after which the same kind of cognitive stimulation sessions will be restarted, with exercises and activities of increased complexity. Each cycle will be structured in sessions aimed at stimulating specific cognitive domains and in sessions focused on multimodal activities. The physical training will include aerobic exercise on an ergometer cycle, whose duration will be increased gradually from 10 to 20 minutes followed by exercises targeted to improve muscle strength, physical function, neuromuscular control and flexibility.
The MCI-training and MCI-no training groups will be compared at T7 in terms of cognitive performances, CBF, gray matter atrophy and inflammatory markers. An additional comparison in terms of cognitive integrity and inflammatory markers will be performed at T14. The SCD-training and SCD-no training groups will be compared at T7 in terms of cognitive performances and inflammatory markers. An additional comparison in terms of cognitive integrity and inflammatory markers will be performed at T14.
The MR acquisitions performed on MCI and SCD subjects at baseline (both T1-weighted and pCASL) will be processed in order to obtain measurements on brain structure volumes and CBF. On these measures a consensus clustering technique will be applied in order to identify homogeneous subgroups of anatomical and CBF patterns on both MCI and SCD cohort.
First, the MCI and SCD cohorts will be treated separately in order to detect subgroups of the different clinical categories.
Second, the MCI and SCD cohorts will be jointly treated in order to detect potential neuroimaging affinity in subjects who exhibit different cognitive impairments.
After the first evaluation with consensus clustering approach, novel clustering techniques such as clustering methods based on deep neural network (Xie et al. 2016) will be explored.
The robustness of clustering methodologies of neuroimaging data will be tested by a cross validation approach and by enriching the sample with anatomical and perfusion data publicly available thanks to the ADNI consortium (at the moment about 160 anatomical and CBF data are available for a cohort of MCI and SCD subjects).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| MCI training | Active comparator | Other: Multidomain cognitive training and physical trainingAfter baseline assessment the MCI-training group will receive a 7 months-long multidomain training, including cognitive, physical exercise and music therapy; Enrolled subjects will be assigned to mixed-gender classes of maximum 10 subjects each and given 2 sessions of 60 minutes supervised cognitive training per day, 3 times a week, and one of 60 minutes supervised aerobic physical activity per day, 3 times a week for 7 months. |
| MCI no-training | No intervention | –Follow up of natural history of subjects after 7 months |
| healthy subjects | No intervention | –Follow up of natural history of subjects after 7 months |
| SCD | No intervention | –Follow up of natural history of subjects after 28 months |
| SCD training | Active comparator | Other: Multidomain cognitive training and physical trainingAfter baseline assessment the MCI-training group will receive a 7 months-long multidomain training, including cognitive, physical exercise and music therapy; Enrolled subjects will be assigned to mixed-gender classes of maximum 10 subjects each and given 2 sessions of 60 minutes supervised cognitive training per day, 3 times a week, and one of 60 minutes supervised aerobic physical activity per day, 3 times a week for 7 months. |
| SCD no-training | No intervention | –Follow up of natural history of subjects after 7 months |
Who may qualify
- Ages
- 65 to 89 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (3 listed)
- age between 65 and 89 years; 5 years of schooling;
- diagnosis of Mild Cognitive Impairment (Croisile et al., 2011) or
- diagnosis of Subjective Cognitive Decline (Jessen et al., 2014).
Key exclusion criteria (3 listed)
- neurological pathologies; dementia;
- psychiatric disorders;
- pathologies or orthopedic problems limiting participation to the aerobic physical training program and to the MR imaging.
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 |
|---|---|---|
| Multidomain cognitive training and physical trainingThe cognitive training programme will be based on 8 cycles composed by 18 sessions of exercises and activities aimed at stimulating multiple cognitive functions. Each cycle will last 3 weeks, after which the same kind of cognitive stimulation sessions will be restarted, with exercises and activities of increased complexity. Each cycle will be structured in sessions aimed at stimulating specific cognitive domains and in sessions focused on multimodal activities (music-therapy, cineforum, etc.). The physical training will include aerobic exercise on an ergometer cycle, whose duration will be increased gradually from 10 to 20 minutes followed by exercises targeted to improve muscle strength, physical function, neuromuscular control and flexibility. | Other | MCI training, SCD training |
Primary outcome
Short term training effects
Time frame: 7 months
The MCI-training and MCI-no training, the SCD-training and SCD-no training groups will be compared at T7 in terms of cognitive performances, CBF, gray matter atrophy (both CBF and GM atrophy will be evaluated on different regions of interest) and inflammatory markers.
1 secondary outcome
Sample stratification
Time frame: 7, 14 and 28 months
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 24 Dec 2024.
- Individual participant dataSharing planned: Undecided. GDPR compliance concerns
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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.
Michela Tosetti, MSc 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 Multidomain cognitive training and physical training in people with MCI and SCD, run by IRCCS Fondazione Stella Maris at 1 site in Italy.
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 3 inclusion and 3 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: looking for participants now, as of the sponsor's last update on 24 Dec 2024. 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 Italy. 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 Paolo Bosco Bosco, PhD (+39 050886180, paolo.bosco@fsm.unipi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Short term training effects (time frame: 7 months). 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 24 Dec 2024.