Alzheimer's Disease (AD)CPLSNCT06953167
Cognitive Health in Ageing Register: Investigational and Observational Trial Studies in Dementia Research (CHARIOT): Prospective Readiness Cohort (PRO) Longitudinal Study
An observational study of Alzheimer's Disease (AD), run by Imperial College London at 1 site in United Kingdom.
Trial summary
Alzheimer's disease is a degenerative condition affecting the brain and is the most frequent form of dementia in older adults. Dementia is currently a major healthcare issue in the UK, affecting approximately a million people. Read more about this study
- Who is it for?
- Ages 65 years and olderHealthy volunteers can take part
- Conditions the study is for
- Alzheimer's Disease (AD)
- How many people
- 600 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 17 Mar 2025to Feb 2029
- Phase
- Observational
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Older adult
Study population: Well characterised cohort of participants who had completed all clinical, cognitive, biochemical and imaging screening assessments (during 2015-2018) required for study entry into CPSS1; were then >60 years old, with documented evidence of amyloid status and were, then, cognitively unimpaired.
Who may be able to join
- To be eligible, participants must meet all inclusion criteria for the study, as follows:
- Male or Female, aged >65years
- Willing and having capacity (as assessed according to MCA 2005) to provide written informed consent and to participate in the study, OR (if lacking capacity) has a nominated consultee (as described in the MCA 2005 and Chapter 11 of the MCA Code of Practice 2007) who is able to advise that this is what the participant would have wished.
- Have completed CPSS1 amyloid screening using either amyloid PET scanning or CSF Aβ42 measurement.
- Be fluent in and able to read and write in English and have adequate hearing and visual acuity to complete the required psychometric tests.
- Be willing and able to adhere to the study visits and assessments specified in this protocol, and the reasonable requests and expectations of the study staff.
- Have a reliable informant - study partner (relative, partner, or friend) who is willing to provide their informed consent to participate, as a source of information. The study partner must be over 18 years old and should be fluent in and able to read and write in English. The informant must have sufficient contact with the participant and sufficient cognitive ability such that the Investigator feels that they can provide meaningful information about the participant's daily functioning. At a minimum, they must be in contact with the participant at least twice per month (in person, via telephone or other audio/visual communication). The study partner will be required in-person at the V1 visit. However, they can complete all subsequent visits remotely, or in-person if required.
Who cannot join
- To be eligible, participants must not meet any of the exclusion criteria for the study, as follows:
- Participant has any disability that would prevent completion of study procedures or assessments (e.g. blindness or significant visual impairment, deafness or significant hearing impairment, speech impairment, or sensory or motor dysfunction), or has any condition or situation/circumstance for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g. compromise the participant's well-being), or that could prevent, limit, or confound the results of protocol-specified assessments and cognitive testing.
- Unable to comply with the study-specific requirements.
- History of alcohol or drug dependence or abuse, as defined by the most current version of the DSM criteria within the last 3 years.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
Imperial College London
London
Project Manager, +44 20 7594 3894, s.vanzan@imperial.ac.uk
About this study
Alzheimer's disease is a degenerative condition affecting the brain and is the most frequent form of dementia in older adults. Dementia is currently a major healthcare issue in the UK, affecting approximately a million people. The progression of the disease varies between individuals and the early stages may be characterised by only minimal changes in memory and thinking. These changes could remain undetected as the symptoms may be mistakenly regarded as normal age-related forgetfulness. However, dementia is not part of the normal ageing process.
The disease process is now known to start at least 20 years prior to the emergence of symptoms. A protein called amyloid starts to deposit in the brain, forming clumps referred to as 'plaques'. Another protein called tau sticks to other tau molecules inside the brain cell and forms structures called 'tangles'. These changes cause damage to the brain cells, disrupting their normal functioning, leading to inflammation and ultimately destruction of the brain cells.
Read more
So far, there is no cure for Alzheimer's disease, but by better understanding the changes that occur over time in the brain, scientists can find ways of detecting and therefore diagnosing and treating the disease earlier. One way in which scientists learn about how a disease develops, is by following people unaffected by the condition over an extended period of time. The same tests and sample collections are repeated to monitor any clinical changes. These are known as longitudinal studies, and CHARIOT:PRO studies are examples of this.
The CHARIOT:PRO Longitudinal Study (CPLS) is an observational study of 600 participants aged >65 years old which aims to evaluate cognition (thinking abilities) and biomarkers (biological markers which indicate the presence of disease e.g. amyloid) over time in older adults. The participants in CPLS were all screened as part of the CHARIOT:PRO Sub-Study (CPSS1) in 2015-2017.
Visit 1 will be conducted within eight weeks after the Study Entry Visit (SEV). Visits 2-7 will follow at six-monthly intervals from Visit 1. During visits, information relating to health, medication, family history of dementia, self-reported cognitive function and anthropometrics will be collected. The cognitive assessments PACC5 and RBANS will be administered along with a measure of executive function (Trail Making Test). Participants will be provided with self-reported questionnaires to be completed at each onsite visit. Blood samples will be taken once a year i.e. Month 0, 12, 24 and 36.
The purpose of CPLS is to continue to build on the vital data and samples already kindly donated by participants screened for CPSS1. This will provide valuable information that will enhance understanding of the earliest stages of Alzheimer's disease before obvious symptoms start to appear. Importantly, the Investigators hope to identify predictive markers of disease, which will help doctors to select the right drugs, and develop other approaches like lifestyle guidance to prevent or delay Alzheimer's disease in the future.
This study is sponsored by Imperial College London, led by the Principal Investigator Professor Lefkos Middleton and is funded by Gates Ventures.
Read the detailed description
The aim of the study is to prospectively evaluate factors and markers associated with varying cognitive performance and longitudinal trajectories in individuals with differing levels of brain amyloid burden cross-sectionally as defined by PET imaging or Aβ42 CSF measurements (at CPSS1 screening), over a period of up to 12 years from CPSS1 screening.
Two C2N assays, i.e. the plasma Precivity AD2 and Multi-Tau assays, will be used at baseline and end -of-study, to assess the amyloid and tau cerebral burden, shown to have a comparable performance to PET and CSF. The former simultaneously quantifies specific plasma amyloid beta and tau peptide concentrations to calculate the Aβ42/40 Ratio and p-tau217/np-tau217(p-tau217 Ratio). The ratios are combined into a proprietary statistical algorithm to calculate the Amyloid Probability Score 2 (APS2), a numerical value ranging from 0-100, that determines whether a patient is Positive (has high likelihood) or Negative (has low likelihood) for the presence of abnormally high brain amyloid plaques by amyloid PET scan.A negative (0 - 47) is consistent with a negative amyloid PET scan; it reflects a low likelihood of brain amyloid plaques and is therefore not consistent with a neuropathological diagnosis of Alzheimer's disease (AD). A positive (48 - 100) is consistent with a positive amyloid PET scan; it reflects a high likelihood of brain amyloid plaques, one of the neuropathological findings of Alzheimer's disease (AD).
The Multi-Tau assay measures the individual values and rations of phosphorylated and non- phosphorylated p/non p-tau 217, p/non p-t181 and p/non p- t205. The presence of high amyloid and/or tau cerebral burden alone does not establish a clinical diagnosis of AD and the APS2 and multi-tau results will be interpreted in conjunction with other patient information and will be clinically correlated.
- Conditions
- Alzheimer's Disease (AD)
- Keywords
- Alzheimer's disease, Dementia, Longitudinal Study, Biomarkers, CHARIOT-PRO, Amyloid, Cognition, Mild Cognitive Impairment
- Medical subject headings
- Alzheimer Disease, Dementia, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Individuals who previously completed CHARIOT:PRO Substudy (CPSS1) screening. | All individuals who completed CPSS1 screening are well-characterised adults now aged >65 years old, with documented measurement of amyloid load and a global CDR score of 0 at the time of CPSS1 screening (2015-2018). They completed all CPSS1 screening assessments including the PACC and RBANS cognitive batteries, physical and neurological evaluation, clinical laboratory tests, quantitative and functional brain MRI studies, and (based on personal choice), either a PET scan or CSF collection via LP. The current project seeks to extend follow-up of CPSS1 study participants for at least another three years. Because CPSS1 screening began in 2015, this three-year follow-up will result in a total follow-up period of up to 12 years from CPSS1 screening for some participants. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Index scores
Raw scores are tallied for each of the 12 subtests and converted into five cognitive domain-specific Index scores (Immediate Memory, Delayed Memory, Language, Attention, Visuospatial Construction). Each Index score has a mean of 100 and an SD of 15, with a range of 40 to 160. Higher RBANS Index scores indicate better cognitive performance.
Measured: 8.5 years
Change from baseline in the Preclinical Alzheimer Cognitive Composite (PACC) component scores
The raw score ranges for each test are as follows: Mini-Mental State Examination (MMSE): 0-30; Logical Memory (Wechsler Memory Scale) - Immediate Recall: 0-25; Delayed Recall: 0-25; Digit Symbol Substitution Test (DSST): 0-93; Free and Cued Selective Reminding Test (FCSRT) - Immediate Recall: 0-48 and Delayed Recall: 0-16; and Category Fluency (alternatively known as semantic fluency): 0-40. Across all PACC components, higher scores indicate better cognitive performance.
Measured: 8.5 years
Secondary outcomes (2)
Change from baseline in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Scale Score
RBANS raw scores are initially tallied for each of the 12 subtests and then converted into Index scores. These combined scores are further converted into a Total Scale Score, adjusted for age. The Total Scale Score is represented as a composite t-score with a mean of 100, a standard deviation (SD) of 15, and a range of 40-160. Higher RBANS Total scores indicate better cognitive performance.
Measured: 8.5 years
Change from baseline in the Preclinical Alzheimer Cognitive Composite (PACC) composite score
Each component score will be transformed into a z-score. These z-scores will then be summed to form the PACC composite score. There is no fixed minimum or maximum for z-scores: a z-score of 0 represents average performance compared to a reference group; a negative z-score indicates below-average performance; and a positive z-score indicates above-average performance. Higher PACC composite scores indicate better cognitive performance.
Measured: 8.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2025
- Study start17 Mar 2025
- Primary completionFeb 2029 (estimated)
- Study completionFeb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer's Disease (AD)Studies of the same condition, open and under way.
- More trials run by Imperial College LondonThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06953167
- Sponsor's protocol ID
- EDGE ID: 174407
- Other IDs
- IRAS: 339745
- Acronym
- CPLS
- Status last verified
- Jan 2026
- First submitted
- 3 Apr 2025
- Last updated
- 21 Jan 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cognitive Health in Ageing Register: Investigational and Observational Trial Studies in Dementia Research (CHARIOT): Prospective Readiness Cohort (PRO) Longitudinal Study
- ClinicalTrials.gov ID
- NCT06953167
- Acronym / sponsor ID
- CPLS / EDGE ID: 174407
- Conditions
- Alzheimer's Disease (AD)
- Keywords
- Alzheimer's disease, Dementia, Longitudinal Study, Biomarkers, CHARIOT-PRO, Amyloid, Cognition, Mild Cognitive Impairment
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- 17 Mar 2025 (actual)
- Primary completion
- Feb 2029 (estimated)
- Study completion
- Feb 2029 (estimated)
- First posted
- 1 May 2025 (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 is a degenerative condition affecting the brain and is the most frequent form of dementia in older adults. Dementia is currently a major healthcare issue in the UK, affecting approximately a million people. The progression of the disease varies between individuals and the early stages may be characterised by only minimal changes in memory and thinking. These changes could remain undetected as the symptoms may be mistakenly regarded as normal age-related forgetfulness. However, dementia is not part of the normal ageing process.
The disease process is now known to start at least 20 years prior to the emergence of symptoms. A protein called amyloid starts to deposit in the brain, forming clumps referred to as 'plaques'. Another protein called tau sticks to other tau molecules inside the brain cell and forms structures called 'tangles'. These changes cause damage to the brain cells, disrupting their normal functioning, leading to inflammation and ultimately destruction of the brain cells.
So far, there is no cure for Alzheimer's disease, but by better understanding the changes that occur over time in the brain, scientists can find ways of detecting and therefore diagnosing and treating the disease earlier. One way in which scientists learn about how a disease develops, is by following people unaffected by the condition over an extended period of time. The same tests and sample collections are repeated to monitor any clinical changes. These are known as longitudinal studies, and CHARIOT:PRO studies are examples of this.
The CHARIOT:PRO Longitudinal Study (CPLS) is an observational study of 600 participants aged >65 years old which aims to evaluate cognition (thinking abilities) and biomarkers (biological markers which indicate the presence of disease e.g. amyloid) over time in older adults. The participants in CPLS were all screened as part of the CHARIOT:PRO Sub-Study (CPSS1) in 2015-2017.
Visit 1 will be conducted within eight weeks after the Study Entry Visit (SEV). Visits 2-7 will follow at six-monthly intervals from Visit 1. During visits, information relating to health, medication, family history of dementia, self-reported cognitive function and anthropometrics will be collected. The cognitive assessments PACC5 and RBANS will be administered along with a measure of executive function (Trail Making Test). Participants will be provided with self-reported questionnaires to be completed at each onsite visit. Blood samples will be taken once a year i.e. Month 0, 12, 24 and 36.
The purpose of CPLS is to continue to build on the vital data and samples already kindly donated by participants screened for CPSS1. This will provide valuable information that will enhance understanding of the earliest stages of Alzheimer's disease before obvious symptoms start to appear. Importantly, the Investigators hope to identify predictive markers of disease, which will help doctors to select the right drugs, and develop other approaches like lifestyle guidance to prevent or delay Alzheimer's disease in the future.
This study is sponsored by Imperial College London, led by the Principal Investigator Professor Lefkos Middleton and is funded by Gates Ventures.
Detailed description
The aim of the study is to prospectively evaluate factors and markers associated with varying cognitive performance and longitudinal trajectories in individuals with differing levels of brain amyloid burden cross-sectionally as defined by PET imaging or Aβ42 CSF measurements (at CPSS1 screening), over a period of up to 12 years from CPSS1 screening.
Two C2N assays, i.e. the plasma Precivity AD2 and Multi-Tau assays, will be used at baseline and end -of-study, to assess the amyloid and tau cerebral burden, shown to have a comparable performance to PET and CSF. The former simultaneously quantifies specific plasma amyloid beta and tau peptide concentrations to calculate the Aβ42/40 Ratio and p-tau217/np-tau217(p-tau217 Ratio). The ratios are combined into a proprietary statistical algorithm to calculate the Amyloid Probability Score 2 (APS2), a numerical value ranging from 0-100, that determines whether a patient is Positive (has high likelihood) or Negative (has low likelihood) for the presence of abnormally high brain amyloid plaques by amyloid PET scan.A negative (0 - 47) is consistent with a negative amyloid PET scan; it reflects a low likelihood of brain amyloid plaques and is therefore not consistent with a neuropathological diagnosis of Alzheimer's disease (AD). A positive (48 - 100) is consistent with a positive amyloid PET scan; it reflects a high likelihood of brain amyloid plaques, one of the neuropathological findings of Alzheimer's disease (AD).
The Multi-Tau assay measures the individual values and rations of phosphorylated and non- phosphorylated p/non p-tau 217, p/non p-t181 and p/non p- t205. The presence of high amyloid and/or tau cerebral burden alone does not establish a clinical diagnosis of AD and the APS2 and multi-tau results will be interpreted in conjunction with other patient information and will be clinically correlated.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Individuals who previously completed CHARIOT:PRO Substudy (CPSS1) screening. | – | –All individuals who completed CPSS1 screening are well-characterised adults now aged >65 years old, with documented measurement of amyloid load and a global CDR score of 0 at the time of CPSS1 screening (2015-2018). They completed all CPSS1 screening assessments including the PACC and RBANS cognitive batteries, physical and neurological evaluation, clinical laboratory tests, quantitative and functional brain MRI studies, and (based on personal choice), either a PET scan or CSF collection via LP. The current project seeks to extend follow-up of CPSS1 study participants for at least another three years. Because CPSS1 screening began in 2015, this three-year follow-up will result in a total follow-up period of up to 12 years from CPSS1 screening for some participants. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
- Study population
- Well characterised cohort of participants who had completed all clinical, cognitive, biochemical and imaging screening assessments (during 2015-2018) required for study entry into CPSS1; were then >60 years old, with documented evidence of amyloid status and were, then, cognitively unimpaired.
Key inclusion criteria (7 listed)
- To be eligible, participants must meet all inclusion criteria for the study, as follows:
Key exclusion criteria (4 listed)
- To be eligible, participants must not meet any of the exclusion criteria for the study, as follows:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change from baseline in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Index scores
Time frame: 8.5 years
Raw scores are tallied for each of the 12 subtests and converted into five cognitive domain-specific Index scores (Immediate Memory, Delayed Memory, Language, Attention, Visuospatial Construction). Each Index score has a mean of 100 and an SD of 15, with a range of 40 to 160. Higher RBANS Index scores indicate better cognitive performance.
Change from baseline in the Preclinical Alzheimer Cognitive Composite (PACC) component scores
Time frame: 8.5 years
The raw score ranges for each test are as follows: Mini-Mental State Examination (MMSE): 0-30; Logical Memory (Wechsler Memory Scale) - Immediate Recall: 0-25; Delayed Recall: 0-25; Digit Symbol Substitution Test (DSST): 0-93; Free and Cued Selective Reminding Test (FCSRT) - Immediate Recall: 0-48 and Delayed Recall: 0-16; and Category Fluency (alternatively known as semantic fluency): 0-40. Across all PACC components, higher scores indicate better cognitive performance.
2 secondary outcomes
Change from baseline in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Scale Score
Time frame: 8.5 years
Change from baseline in the Preclinical Alzheimer Cognitive Composite (PACC) composite score
Time frame: 8.5 years
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 21 Jan 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Alzheimer's Disease (AD), run by Imperial College London at 1 site in United Kingdom.
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 7 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: looking for participants now, as of the sponsor's last update on 21 Jan 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 Kingdom. 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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Index scores (time frame: 8.5 years). The study lists 2 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 21 Jan 2026.