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Alzheimer's DementiaEPAD-LCSNCT02804789

European Prevention of Alzheimer's Dementia (EPAD) Longitudinal Cohort Study (LCS)

An observational study of Alzheimer's Dementia, run by University of Edinburgh at 30 sites in 9 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Brain changes associated with Alzheimer's disease may precede symptoms of Alzheimer's Dementia by over 20 years. The Investigators hope to be able to identify Alzheimer's disease at its very earliest stages when in theory treatments are most likely to be successful in preventing further spread of the disease in the… Read more about this study

Who is it for?
Ages 50 years and olderHealthy volunteers can take part
Conditions the study is for
Alzheimer's Dementia
How many people
2,095 participants
Where
30 sitesin 9 countries
Study dates
May 2016to 13 Mar 2020
How long will I take part?
44 Months
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Study population: Research participants will mainly be recruited from existing Parent Cohorts (PC) across Europe. PCs considered for EPAD are: active cohorts without dementia aged at least 50 years; the PC PI is willing to provide research participants for EPAD trials; with existing consent for re-contact or possibility to obtain consent to re-contact. Potential research participants will be identified based on data in the PC, using a flexible search algorithm adapted to the types of data available in each PC. Recruitment will be complemented with research participants who are recruited from a clinical setting by their referring clinician. In case an individual or their referring clinician contacts a TDC, the referring clinician will check the flexible algorithm to confirm their suitability.

Who may be able to join

  • At least 50 Years of Age
  • Characterisation of cognitive, biomarker and risk factors (genetic, environmental) status of research participants based on data collected at the EPAD screening/baseline visit, so that decisions on selection/deselection can be made with reference to the dual needs of having sufficient heterogeneity across the entire probability-spectrum population for disease-modelling work, and suitable research participants for the EPAD PoC trial (Balancing Committee decision)
  • Able to read and write with a minimum of 7 years of formal education.
  • Willing in principle to participate in the EPAD Proof of Concept Trials (with additional consent).
  • Have a study partner or can identify someone willing to be a study partner. The primary role of the study partner will be as informant. They will also receive oral and written information about the EPAD LCS, and will sign an Informed Consent Form (ICF).

Who cannot join

  • Individuals who fulfill diagnostic criteria for any type of dementia.
  • Clinical Dementia Rating >=1
  • Known carriers of a Presenilin (PSEN) 1, PSEN 2 or Amyloid Precursor Protein (APP) mutation associated with Autosomal Dominant Alzheimer's dementia or any other neurodegenerative disease.
  • Presence of any neurological, psychiatric or medical conditions associated with a long-term risk of significant cognitive impairment or dementia including but not limited to pre- manifest Huntington's disease, multiple sclerosis, Parkinson's disease, Down syndrome, active alcohol/drug abuse; or major psychiatric disorders including current major depressive disorder, schizophrenia, schizoaffective or bipolar disorder.
  • Cancer or history of cancer in the last 5 years (excluding cutaneous basal or squamous cell cancer resolved by excision).
  • Any current medical conditions that are clinically significant and might make participation in an investigational trial unsafe, e.g., uncontrolled or unstable disease of any major organ system; history within the last 6 months of any acute illness of a major organ system requiring emergency care or hospitalization, including revascularization procedures; severe renal or hepatic failure; unstable or poorly controlled DM, hypertension, or heart failure; malignant neoplasms within the last 3 years (expect for basal or squamous cell carcinoma in situ of the skin, or localized prostate cancer in male participants); any clinically relevant abnormalities in blood parameters included in local TDC routine assessments; severe loss of vision, hearing or communicative ability; or any conditions preventing co-operation or completion of the required assessments in the trial, as judged by the investigator.
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  • Contraindications for MRI/Positron emission tomography (PET) Scan.
  • Contraindications for Lumbar Puncture.
  • Any evidence of intracranial pathology which, in the opinion of the Investigator, may affect cognition including but not limited to brain tumours (benign or malignant), aneurysm or arteriovenous malformations, territorial stroke (excluding smaller watershed strokes), recent haemorrhage (parenchymal or subdural), or obstructive hydrocephalus. Research participants with a MRI scan demonstrating markers of small vessel disease (e.g. white matter changes or lacunar infarcts) judged to be clinically insignificant, or microbleeds are allowed.
  • Participation in a clinical trial of an Investigational Product (CTIMP) in the last 30 days (continued participation in the parent cohort is expected). Participation in a non-CTIMP is not an exclusion criterion.
  • Diminished decision-making capacity/ not capable of consenting at Visit 1 or Visit 2. If at a subsequent annual EPAD LCS visit health professionals suspect diminished consent capacity according to local TDC routine procedures, a formal assessment of the research participant's capacity to consent will be conducted. The participant will be offered the opportunity to continue in the EPAD LCS under suitable local regulations regarding capacitous participants who have consented to enter a longitudinal study who subsequently loose capacity. Capacity will be assessed at each study visit using the correct legal framework.

Trial locations and contacts

30 sites in 9 countries.

30 sites in 9 countries

United Kingdom10 sites

  • NHS Grampian

    Aberdeen, AB25 2ZH

  • North Bristol NHS Trust

    Bristol, BS10 5NB

  • University of Cambridge; Department of Clinical Neurosciences

    Cambridge, CB2 0SZ

  • Monklands University Hospital

    Cumbernauld, Lanarkshire, G67 3BE

  • NHS Tayside

    Dundee, DD1 9SY

  • University of Edinburgh, Centre for Dementia Prevention

    Edinburgh, Midlothian, EH16 4UX

  • Glasgow Clinical Research Facility; NHS Greater Glasgow and Clyde

    Glasgow, G51 4TF

  • West London Mental Health NHS Trust

    London, TW7 6FY

  • Greater Manchester Clinical Research Network

    Manchester, M13 9WL

  • University of Oxford, Department of Psychiatry

    Oxford, OX3 7JX

Other trials in United Kingdom

France6 sites

  • CMRR du CHRU de Lille Hôpital Roger Salengro

    Lille, 59037 CEDEX

  • CHU Gui de Chauliac Département de Neurologie

    Montpellier, 34295 CEDEX 5

  • Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal

    Paris, 75475 CEDEX 10

  • Hôpital Universitaire de la Pitié Salpêtrière

    Paris, 75651 CEDEX 13

  • CMRR- Hôpital Laënnec Nord - CIC Neurologie / CHU de Nantes

    Saint-Herblain, 44800

  • Toulouse University Hospital / Gérontopôle-Research Clinical Center

    Toulouse, 31059 Cedex 9

Other trials in France

Spain4 sites

  • BarcelonaBeta Brain Research Centre

    Barcelona, 08005

  • Fundacion ACE, Institut Catala de Neurocienies Aplicades

    Barcelona, 08028

  • Fundacion CITA-alzheimer Fundazioa, Center for Research and Advanced Therapies

    San Sebastián, 20009

  • Unidade Deterioro Cognitivo, Servicio de Neurologia, Hospital Universitario

    Santander, Cantabria, 39008

Other trials in Spain

Belgium2 sites

  • Cliniques Universitaires Saint-Luc ASBL, Neurology Department

    Brussels, 1200

  • UZ Leuven, Campus Gasthuisberg

    Leuven, 3000

Other trials in Belgium

Italy2 sites

  • IRCCS San Giovanni di Dio - Fatebenefratelli

    Brescia, 25125

  • Univerita di Perugia, Centro Disturbi della Memoria, Clinica Neurologica

    Perugia, Loc. S Andrea Delle Fratte, 06132

Other trials in Italy

Sweden2 sites

  • Neuropsychiatric Research Unit, Sahlgrenska University Hoospital

    Gothenburg, Västra Götaland County, SE-431 41

  • Karolinska Institutet

    Stockholm, SE-141 86

Other trials in Sweden

Switzerland2 sites

  • Hôpitaux Universitaires de Genève - HUG

    Geneva, CH-1227

  • Centre Leenaards de la memoire- CHUV, Department of Neurosciences cliniques

    Lausanne, 1011

Other trials in Switzerland

Greece1 site

  • National and Kapodistran, University of Athens, 1st Department of Neurology, Aeginition Hospital

    Athens, 11528

Other trials in Greece

Netherlands1 site

  • VUmc Alzheimer Center and Alzheimer Research Center

    Amsterdam, North Holland, 1081GM

Other trials in Netherlands

About this study

Brain changes associated with Alzheimer's disease may precede symptoms of Alzheimer's Dementia by over 20 years. The Investigators hope to be able to identify Alzheimer's disease at its very earliest stages when in theory treatments are most likely to be successful in preventing further spread of the disease in the brain and causing dementia. The aim of EPAD programme is to develop new treatments more quickly to prevent Alzheimer's dementia. A major component of the EPAD programme is the EPAD Longitudinal Cohort Study which can provide subjects for the EPAD trial as well as data to improve understanding of disease before dementia develops.

The Investigators will approach a broad range of people over the age of 50 who have previously taken part in various research studies and consented to being recontacted for further research. Participants will be asked questions to assess their memory and other cognitive function. The participants will also undertake a brain scan, provide a sample of spinal fluid, blood, urine and saliva to look at markers in these bodily fluids that may change in Alzheimer's disease. The Investigators will then follow these participants until December 2019 repeating these tests annually. This will be called the EPAD Longitudinal Cohort Study (EPAD LCS). The main reasons for EPAD developing a cohort are to help the Investigators understand more about what happens to people before dementia develops, and to help recruit people more quickly into the EPAD trials of new medications or other interventions expected to prevent dementia.

People in the EPAD LCS may be invited to take part in the EPAD Proof of Concept prevention studies to see if interventions can modify the probability of developing dementia or cognitive problems (this will be subject to separate ethics approval and consent). Together EPAD LCS and EPAD PoC make up the full EPAD Programme.

Read the detailed description

The EPAD project has been established to overcome the major hurdles hampering drug development for secondary prevention of AD dementia, by conducting the EPAD LCS (fed mainly from existing Parent Cohorts (PC) across Europe) in alignment with the adaptive design EPAD PoC trial. Both EPAD LCS and EPAD PoC trial will be run in an exclusive network of highly selected, expert Trial Delivery Centres (TDC) that will be selected on the basis of strictly applied criteria to ensure the highest possible data quality, successful recruitment and adherence to the EPAD principles.

While interventions must start early in the course of AD, accurate disease models covering the entire course of AD before dementia onset are lacking. Estimating with reasonable confidence an individual's overall probability of developing AD dementia over a defined time period must take into account multiple dimensions simultaneously (e.g. cognition, biomarkers, traditional risk factors - genetic and environmental). This will allow any given individual to be placed somewhere on a probability spectrum from negligible probability to high probability. Because individuals with similar overall probability may have very different contributions from various components in each dimension, flexible algorithms are needed instead of simple cut-offs to identify a probability-spectrum population adequate for both disease modelling and for providing a sufficient number of potential trial participants (especially in adaptive trials with multiple arms testing drugs with different mechanisms of action).

EPAD LCS is designed to address the dual need for development of accurate longitudinal models for AD covering the entire disease course, and development of adequate infrastructure for facilitating identification of research participants and clinical trial recruitment. EPAD LCS will have a probability-spectrum population selected mostly from already existing PCs across Europe to facilitate fast recruitment. Different types of PCs will be considered (e.g. memory clinic-based, population-based). Due to the variety of PCs, some EPAD LCS research participants will be e.g. memory clinic patients without dementia, while others will be e.g. participants without dementia from the general population. The variety of PC settings will ensure that the EPAD LCS probability-spectrum population can cover the entire continuum of probability for AD dementia development. Regular EPAD LCS follow-up with clinical, cognitive and biomarker assessments will provide a well-phenotyped probability-spectrum population, generating high-quality data for updating disease models, for easier identification of individuals suitable for trial inclusion, and for use as trial run-in data and reference for evaluating intervention efficacy.

The flow of research participants from the population at large to the trial is divided into the following stages: firstly, EPAD will engage existing PCs from across Europe who may have eligible research participants for the EPAD LCS. The next step is drawing research participants from the PCs into the EPAD LCS to maintain a suitable population of approximately 6,000 research participants. Recruitment will be complemented with research participants who are recruited from a clinical setting by their referring clinician. To enable access to the EPAD LCS for these potential participants, the referring clinician will check if they match the flexible algorithm. Finally, research participants in the EPAD LCS who fulfil trial inclusion criteria (approximately 1,500 research participants), will be invited to enter the EPAD PoC (PoC) trial for evaluation of treatment for secondary prevention of AD dementia. This trial is a standing, adaptive, PoC trial that could involve multiple arms running concurrently. Successful graduation through PoC into phase 3 confirmatory trials of single or combinatorial interventions will be based on success against an intermediary, target specific biomarker and then success against a cognitive measure.

Once recruitment is completed, at any given time there should be approx. 6,000 research participants in the EPAD LCS and approx. 1,500 in the EPAD PoC, hence the need to replenish each from PCs as participants are lost through attrition. EPAD LCS will initially run until the end of December 2019, and extension of consent will be sought after 4 years.

Keywords
Prevention
Medical subject headings
Alzheimer Disease

What is being measured

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

  1. Change in RBANS Composite score over time, units on a scale.

    Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Composite score combining: List Learning \& Story Memory; Figure Recall; Figure Copy \& Line Orientation; Picture Naming; Semantic Fluency, Digit Span, Coding.

    Measured: Measured at Baseline, 6 months, year 1, year 2, year 3.

Secondary outcomes (5)

  1. Change in other Secondary Cognitive Tests score: Working Memory, over time, units on a scale.

    Dot Counting test

    Measured: Measured at Baseline, 6 months, year 1, year 2, year 3

  2. Change in other Secondary Cognitive Tests score: Choice Reaction Time and Set Shifting, over time, units on a scale.

    Flanker test

    Measured: Measured at Baseline, 6 months, year 1, year 2, year 3

  3. Change in other Secondary Cognitive Tests score: Paired Associate Learning, over time, units on a scale.

    Favourites

    Measured: Measured at Baseline, 6 months, year 1, year 2, year 3

  4. Change in cerebrospinal fluid (CSF) AD biomarkers over time

    Aβ, t-tau and p-tau levels in pg/ml

    Measured: Measured at Baseline, year 1, year 2, year 3

  5. Changes in neuro-imaging assessment of hippocampal and whole brain volume, over time

    Hippocampal and whole brain volume, cm3

    Measured: Measured at Baseline, year 1, year 2, year 3

Timeline

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

  1. First posted17 Jun 2016 (estimated)
  2. Study startMay 2016
  3. Primary completion13 Mar 2020
  4. Study completion13 Mar 2020

Why it stopped: No further funding available, remaining visits halted due to threat of Covid 19

Resources

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
Prospective
Enrolment
2,095 participants (actual)
Target duration
44 Months
IDs, dates and publications
ClinicalTrials.gov ID
NCT02804789
Sponsor's protocol ID
EPAD-UoE-001
Acronym
EPAD-LCS
Status last verified
Mar 2020
First submitted
9 May 2016
Last updated
31 Mar 2020
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Yes: EPAD is an Innovative Medicines Initiative (IMI) project with open access to data.

Publications

  • Osset-Malla M, Martinez-Velasco A, Sanchez-Benavides G, Buongiorno M, de la Sierra A, Shekari M, Minguillon C, Kollmorgen G, Quijano-Rubio C, Zetterberg H, Blennow K, Garcia DV, Suarez-Calvet M, Gispert JD, Grau-Rivera O; ALFA Study. Blood pressure and Alzheimer's disease biomarkers in cognitively unimpaired adults: a multicenter study. J Prev Alzheimers Dis. 2025 Dec;12(10):100304. doi: 10.1016/j.tjpad.2025.100304. Epub 2025 Aug 11.

    PubMed 40796457

  • Vermunt L, Muniz-Terrera G, Ter Meulen L, Veal C, Blennow K, Campbell A, Carrie I, Delrieu J, Fauria K, Huesa Rodriguez G, Ingala S, Jenkins N, Molinuevo JL, Ousset PJ, Porteous D, Prins ND, Solomon A, Tom BD, Zetterberg H, Zwan M, Ritchie CW, Scheltens P, Luscan G, Brookes AJ, Visser PJ; IMI-EPAD collaborators. Prescreening for European Prevention of Alzheimer Dementia (EPAD) trial-ready cohort: impact of AD risk factors and recruitment settings. Alzheimers Res Ther. 2020 Jan 6;12(1):8. doi: 10.1186/s13195-019-0576-y.

    PubMed 31907067

  • Solomon A, Kivipelto M, Molinuevo JL, Tom B, Ritchie CW; EPAD Consortium. European Prevention of Alzheimer's Dementia Longitudinal Cohort Study (EPAD LCS): study protocol. BMJ Open. 2019 Feb 19;8(12):e021017. doi: 10.1136/bmjopen-2017-021017.

    PubMed 30782589

Questions about this trial

What is this clinical trial studying?

An observational study of Alzheimer's Dementia, run by University of Edinburgh at 30 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 31 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 30 sites in United Kingdom, France, Spain, Belgium, Italy and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study was stopped early (reason given: No further funding available, remaining visits halted due to threat of Covid 19). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in RBANS Composite score over time, units on a scale. (time frame: Measured at Baseline, 6 months, year 1, year 2, year 3.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02804789, which also lists 3 linked publications.

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 31 Mar 2020.

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