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

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ClinicalTrials.gov Identifier: NCT02804789
Recruitment Status : Recruiting
First Posted : June 17, 2016
Last Update Posted : March 22, 2018
Sponsor:
Collaborator:
Innovative Medicines Initiative
Information provided by (Responsible Party):
University of Edinburgh

Brief 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 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.


Condition or disease
Alzheimer's Dementia

  Show Detailed Description

Study Type : Observational [Patient Registry]
Estimated Enrollment : 6000 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 44 Months
Official Title: European Prevention of Alzheimer's Dementia (EPAD) Longitudinal Cohort Study (LCS)
Study Start Date : May 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019





Primary Outcome Measures :
  1. Change in RBANS Composite score over time, units on a scale. [ Time Frame: Measured at Baseline, 6 months, year 1, year 2, year 3. ]
    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.


Secondary Outcome Measures :
  1. Change in other Secondary Cognitive Tests score: Working Memory, over time, units on a scale. [ Time Frame: Measured at Baseline, 6 months, year 1, year 2, year 3 ]
    Dot Counting test

  2. Change in other Secondary Cognitive Tests score: Choice Reaction Time and Set Shifting, over time, units on a scale. [ Time Frame: Measured at Baseline, 6 months, year 1, year 2, year 3 ]
    Flanker test

  3. Change in other Secondary Cognitive Tests score: Paired Associate Learning, over time, units on a scale. [ Time Frame: Measured at Baseline, 6 months, year 1, year 2, year 3 ]
    Favourites

  4. Change in cerebrospinal fluid (CSF) AD biomarkers over time [ Time Frame: Measured at Baseline, year 1, year 2, year 3 ]
    Aβ, t-tau and p-tau levels in pg/ml

  5. Changes in neuro-imaging assessment of hippocampal and whole brain volume, over time [ Time Frame: Measured at Baseline, year 1, year 2, year 3 ]
    Hippocampal and whole brain volume, cm3


Other Outcome Measures:
  1. Change in exploratory Cognitive Tests score: Allocentric space, over time, units on a scale. [ Time Frame: Measured at Baseline, 6 months, year 1, year 2, year 3 ]
    Four Mountains Test

  2. Change in exploratory Cognitive Tests score: Egocentric space, over time, units on a scale. [ Time Frame: Measured at Baseline, 6 months, year 1, year 2, year 3 ]
    Supermarket Trolley Virtual Reality Test

  3. Change in other secondary clinical outcome scale: Everyday functioning, total over time, units on a scale [ Time Frame: Measured at Baseline, 6 months, year 1, year 2, year 3 ]
    Everyday functioning: Amsterdam Instrumental Activities of Daily Living Questionnaire.

  4. Changes in neuro-imaging assessments over time, Multi-regional Structural and Functional MRI & Functional regional and network measures, units on a scale [ Time Frame: Measured at Baseline, year 1, year 2, year 3 ]
    Cortical thickness, deep grey matter (GM) volumes, Fractional anisotropy (FA) of temporal lobe, diffusion kurtosis (multi b-value DTI), network alterations, Global & parietal Cerebral Blood Flow (CBF), Changes within the default-mode network (DMN) & relation with hippocampal activity (rsfMRI), Bolus arrival time (multi-delay ASL), Network analysis (rsfMRI)

  5. Changes in Lifestyle factors over time: Smoking [ Time Frame: Measured at Baseline, year 1, year 2, year 3 ]
    Smoking: never/past/current

  6. Changes in Lifestyle factors over time: Alcohol Consumption [ Time Frame: Measured at Baseline, year 1, year 2, year 3 ]
    Alcohol: units/week

  7. Changes in Lifestyle factors over time: drug abuse/misuse [ Time Frame: Measured at Baseline, year 1, year 2, year 3 ]
    Drug abuse/misuse: never/past/current

  8. Changes in Lifestyle factors over time: diet HATICE (Healthy Aging through Internet Counselling in the Elderly), units on a scale [ Time Frame: Measured at Baseline, year 1, year 2, year 3 ]
    Diet questionnaire: HATICE (Healthy Aging through Internet Counselling in the Elderly), physical activity.

  9. Changes in Lifestyle factors over time: physical activity frequency [ Time Frame: Measured at Baseline, year 1, year 2, year 3 ]
    Physical activity: daily, 2-3 times/week, 2-3 times/month, a few times a year, not at all

  10. Changes in Lifestyle factors over time: Life events over time [ Time Frame: Measured at Baseline, year 1, year 2, year 3 ]
    Life events: SNAC (Swedish National study on Ageing and Care).

  11. Changes in Lifestyle factors over time: Self-rated health and fitness [ Time Frame: Measured at Baseline, year 1, year 2, year 3 ]
    Self-rated health and fitness: Very good/good/satisfactory/relatively poor/poor

  12. Change in Mini-Mental Satus Exam (MMSE) over time [ Time Frame: Measured at Baseline, year 1, year 2, year 3 ]
    Measure of clinical state

  13. Change in Clinical Dementia Rating Scale (CDR) over time [ Time Frame: Measured at Baseline, year 1, year 2, year 3 ]
    Assessment of six domains, (memory, orientation, judgement and problem solving, community affairs, home and hobbies and personal care), from which the global CDR score, CDR sum of notes and a CDR rating for each domain are calculated.

  14. Change in other clinical outcome scale: Depression, total over time, units on a scale [ Time Frame: Measured at Baseline, year 1, year 2, year 3 ]
    Depression: Geriatric Depression Scale

  15. Change in other clinical outcome scale: Anxiety, total over time, units on a scale [ Time Frame: Measured at Baseline, year 1, year 2, year 3 ]
    Anxiety: State-Trait Anxiety Inventory

  16. Change in other clinical outcome scale: Sleep, total over time, units on a scale [ Time Frame: Measured at Baseline, year 1, year 2, year 3 ]
    Sleep: Pittsburgh Sleep Quality Index

  17. Other neuro-imaging measure: Vascular Burden, over time, units on a scale [ Time Frame: Measured at Baseline, year 1, year 2, year 3 ]
    Vascular Burden: Counts of White Matter Lesions, infarcts, laciness, micro bleeds and superficial siderosis.

  18. Other clinical outcome: Dementia Diagnosed by a Participant's Physician [ Time Frame: Measured at Baseline, year 1, year 2, year 3 ]
    Type of Dementia and Date of Diagnosis

  19. Genetic Assessment of apolipoprotein E (ApoE) genotype [ Time Frame: Measured at Baseline ]
    APOE genotype determined by allele combination of e2, e3 and e4

  20. Sociodemographic Factors (subject to local regulations [ Time Frame: Measured at Baseline ]
    Date of Birth, Age, Ethnicity, Education, Marital Status, Handedness

  21. Other clinical measure: Family History of AD [ Time Frame: Measured at Baseline ]
    Family history of AD in number of family members of first degree with history compatible with AD

  22. Other clinical measure: Medical History [ Time Frame: Measured at Baseline, year 1, year 2, year 3 ]
    Medical History: Yes/No for: Stroke, Diabetes (type 1 or 2), Hypertension, Hypercholesterolemia, Myocardial Infarction, Chronic Ischemic Heart Disease, Chronic Obstructive Pulmonary Disease, Asthma, Depression, Rheumatoid Arthritis, Any Cancer, General Anaesthesia after the age of 50 years, Head Injury assessed with the Brain Injury Screening Questionnaire (BISQ), Mild Cognitive Impairment, Other Conditions (Listed as free text)

  23. Other clinical measure: Current Medication [ Time Frame: Measured at Baseline, year 1, year 2, year 3 ]
    Drug, treatment duration (<1year / 1-5years / >5years)

  24. Other clinical measure: Body Height [ Time Frame: Measured at Baseline ]
    Body Height: without shoes, measured to the nearest cm

  25. Other clinical measure: Body Weight [ Time Frame: Measured at Baseline, year 1, year 2, year 3 ]
    Body Weight: measured to the nearest 0.1kg

  26. Other clinical measure: Hip-waist Circumference [ Time Frame: Measured at Baseline, year 1, year 2, year 3 ]
    Hip-waist Circumference: measured to nearest 0.1cm


Biospecimen Retention:   Samples With DNA
  • Urine
  • Saliva
  • CSF
  • Blood (Serum, Plasma, Whole Blood, RNA, DNA)


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
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.
Criteria

Inclusion Criteria:

  1. At least 50 Years of Age
  2. 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)
  3. Able to read and write with a minimum of 7 years of formal education.
  4. Willing in principle to participate in the EPAD Proof of Concept Trials (with additional consent).
  5. 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).

Exclusion Criteria:

  1. Individuals who fulfill diagnostic criteria for any type of dementia.
  2. Clinical Dementia Rating >=1
  3. 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.
  4. 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.
  5. Cancer or history of cancer in the last 5 years (excluding cutaneous basal or squamous cell cancer resolved by excision).
  6. 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.
  7. Contraindications for MRI/Positron emission tomography (PET) Scan.
  8. Contraindications for Lumbar Puncture.
  9. 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.
  10. 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02804789


Contacts
Contact: Craig Ritchie craig.ritchie@ed.ac.uk
Contact: Ellie McMaster ellie.mcmaster@ed.ac.uk

Locations
France
CMRR du CHRU de Lille Hôpital Roger Salengro Recruiting
Lille, France, 59037 CEDEX
Contact: Melanie Leroy       melanie.leroy@chru-lille.fr   
Principal Investigator: Florence Pasquier         
CHU Gui de Chauliac Département de Neurologie Recruiting
Montpellier, France, 34295 CEDEX 5
Contact: Caroline Grasseli       caroline.grasselli@orange.fr   
Principal Investigator: Audrey Gabelle Deloustal         
Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal Recruiting
Paris, France, 75475 CEDEX 10
Contact: Alexandra Fayel       foyel.alexandra@gmail.com   
Principal Investigator: Julien Dumurgier         
Hôpital Universitaire de la Pitié Salpêtrière Recruiting
Paris, France, 75651 CEDEX 13
Contact: Leslie Ameil       leslie.ameil@wanadoo.fr   
Principal Investigator: Bruno Dubois         
CMRR- Hôpital Laënnec Nord - CIC Neurologie / CHU de Nantes Recruiting
Saint-Herblain, France, 44800
Contact: Romain Muraz       romain.muraz@chu-nantes.fr   
Principal Investigator: Claire Bouteleau Bretonnière         
Toulouse University Hospital / Gérontopôle-Research Clinical Center Recruiting
Toulouse, France, 31059 Cedex 9
Contact: Isabelle Carrie    0033 5617 764 59    carrie.i@chu-toulouse.fr   
Principal Investigator: Bruno Vellas         
Italy
IRCCS San Giovanni di Dio - Fatebenefratelli Not yet recruiting
Brescia, Italy, 25125
Contact: Monica Almici       malmici@fatebenefratelli.eu   
Principal Investigator: Samanta Galluzzi         
Netherlands
VUmc Alzheimer Center and Alzheimer Research Center Recruiting
Amsterdam, Noord Holland, Netherlands, 1081GM
Contact: Casper de Boer       c.deboer2@vumc.nl   
Principal Investigator: Philip Scheltens         
Sub-Investigator: Niels Prins         
Spain
BarcelonaBeta Brain Research Centre Recruiting
Barcelona, Spain, 08005
Contact: Gonzalo Sanchez Benavides    0034 933 160 988    gsanchezb@fpmaragall.org   
Principal Investigator: Jose Luis Dr Molineuvo, MD, PhD         
Fundacion CITA-alzheimer Fundazioa, Center for Research and Advanced Therapies Recruiting
San Sebastián, Spain, 20009
Contact: Jon Saldias Iriarte    0034 943021792    jsaldias@cita-alzheimer.org   
Principal Investigator: Pablo Martinez-Lage         
Sweden
Karolinska Institutet Recruiting
Stockholm, Sweden, SE-141 86
Contact: Marie Lärksäter    0046 8585 854 68    marie.larksater@karolinska.se   
Contact: Stefan Borg    +46(0)737121337    stefan.borg.1@ki.se   
Principal Investigator: Miia Kivipelto         
Switzerland
Hôpitaux Universitaires de Genève - HUG Recruiting
Geneva, Switzerland, CH-1227
Contact: Maura Parapini       maura.parapini@unige.ch   
Principal Investigator: Giovanni Frisoni         
United Kingdom
University of Edinburgh, Centre for Dementia Prevention Recruiting
Edinburgh, Midlothian, United Kingdom, EH16 4UX
Contact: Sarah D Gregory    +44 131 650 6794    sarah.gregory@ed.ac.uk   
Principal Investigator: Craig Ritchie, MD PhD         
Sub-Investigator: Hinesh Topiwala, MD         
NHS Grampian Recruiting
Aberdeen, United Kingdom, AB25 2ZH
Contact: Emma Darling       emma.darling1@nhs.net   
Contact: Kirsten McClelland-Brooks       Kirsten.McClelland-Brooks@nhs.net   
Principal Investigator: Alasdair Lawrie         
North Bristol NHS Trust Not yet recruiting
Bristol, United Kingdom, BS10 5NB
Contact: Natalie Rosewell       natalie.rosewell@nbt.nhs.uk   
Principal Investigator: Elizabeth Coulthard         
Sub-Investigator: Natalie Rosewell         
University of Cambridge; Department of Clinical Neurosciences Not yet recruiting
Cambridge, United Kingdom, CB2 0SZ
Contact: Dennis Chan    0044 122 376 0696    dc598@cam.ac.uk   
Principal Investigator: Dennis Chan         
NHS Tayside Recruiting
Dundee, United Kingdom, DD1 9SY
Contact: Tiffany Stewart       tstewart2@nhs.net   
Principal Investigator: Peter Connelly         
Glasgow Clinical Research Facility; NHS Greater Glasgow and Clyde Recruiting
Glasgow, United Kingdom, G51 4TF
Contact: Catriona McNeill       catrionamcneill@nhs.net   
Principal Investigator: Derek Brown         
West London Mental Health NHS Trust Not yet recruiting
London, United Kingdom, TW7 6FY
Contact: Genevieve Morrison    0044 208 483 1834    Genevieve.Morrison@wlmht.nhs.uk   
Principal Investigator: Paresh Malhotra         
Greater Manchester Clinical Research Network Not yet recruiting
Manchester, United Kingdom, M13 9WL
Contact: Rowen Norton    0044 161 701 5604    rowen.norton@nihr.ac.uk   
Principal Investigator: Iracema Leroi         
University of Oxford, Department of Psychiatry Recruiting
Oxford, United Kingdom, OX3 7JX
Contact: Vanashree Sexton    0044 1865 613132    vanashree.sexton@psych.ox.ac.uk   
Principal Investigator: Vanessa Raymont         
Sponsors and Collaborators
University of Edinburgh
Innovative Medicines Initiative
Investigators
Principal Investigator: Craig Ritchie University of Edinburgh

Responsible Party: University of Edinburgh
ClinicalTrials.gov Identifier: NCT02804789     History of Changes
Other Study ID Numbers: EPAD-UoE-001
First Posted: June 17, 2016    Key Record Dates
Last Update Posted: March 22, 2018
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: EPAD is an Innovative Medicines Initiative (IMI) project with open access to data.
Time Frame: Post December 2019
Access Criteria: To be determined by the EPAD Research Access Committee

Keywords provided by University of Edinburgh:
Prevention

Additional relevant MeSH terms:
Dementia
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Tauopathies
Neurodegenerative Diseases