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Dominantly Inherited Alzheimer Network (DIAN) (DIAN)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2016 by Washington University School of Medicine
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00869817
First received: March 25, 2009
Last updated: June 8, 2016
Last verified: June 2016
  Purpose
The purpose of this study is to identify potential biomarkers that may predict the development of Alzheimer's disease in people who carry an Alzheimer's mutation.

Condition
Alzheimer's Disease

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Dominantly Inherited Alzheimer Network (DIAN)

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Positive predictive power of a biomarker or group of biomarkers [ Time Frame: Variable follow-up assessment based on age in relation to age at onset of affected parent. ] [ Designated as safety issue: No ]
  • Biomarkers obtained by blood draw, lumbar puncture, MRI, FDG PET, PET amyloid imaging [ Time Frame: Variable follow-up assessment based on age in relation to age at onset of affected parent ] [ Designated as safety issue: No ]
  • Clinical markers also examined from clinical interview and cognitive testing [ Time Frame: Variable follow-up assessment based on age in relation to age at onset of affected parent ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA
serum, plasma, cerebral spinal fluid

Estimated Enrollment: 600
Study Start Date: January 2009
Estimated Study Completion Date: June 2019
Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)
Groups/Cohorts
1
Mutation Positive
2
Mutation Negative

Detailed Description:

Dominantly inherited Alzheimer's disease (AD) represents less than 1% of all cases of AD and is an important model for study because the responsible mutations have known biochemical consequences that are believed to underlie the pathological basis of the disorder. Three major hypotheses will be tested:

  • First, that there is a period of preclinical (presymptomatic) AD in individuals who are destined to develop early-onset dementia (gene carriers) that can be detected by changes in biological fluids and in neuroimaging correlates in comparison with individuals who will not develop early-onset dementia (non-carriers).
  • Second, because all identified causative mutations for AD affect the normal processing of amyloid precursor protein (APP) and increase brain levels of amyloid-beta 42 (Aβ42), the sequence of preclinical changes initially will involve Aβ42 (production and clearance; reduced levels in cerebrospinal fluid [CSF]), followed by evidence for cerebral deposition of Aβ42 (amyloid imaging), followed by cerebral metabolic activity (functional imaging), and finally by regional atrophy (structural imaging).
  • Finally, that the phenotype of symptomatic early-onset familial AD, including its clinical course, is similar to that of late-onset "sporadic" AD.

The following specific aims will be used to test these hypotheses:

  1. Maintain the established international DIAN registry of individuals (mutation carriers and non-carriers; pre-symptomatic and symptomatic) who are biological adult children of a parent with a known causative mutation for AD in the APP, PSEN1, or PSEN2 genes and assess participants every 2 years with the uniform DIAN protocol.
  2. Maintain the integrated DIAN database and biospecimen repository to disseminate data and tissue to qualified investigators (within and outside of DIAN) in a user-friendly manner and to permit analyses within, between, and among the various data domains that will include:

    1. In asymptomatic mutation carriers (using non-carriers as controls), determine the temporal ordering and rate of intraindividual change in clinical, cognitive, behavioral, imaging, and fluid biomarkers of AD prior to estimated age of symptom onset.
    2. In symptomatic mutation carriers, compare the clinical and neuropathological phenotypes of ADAD to those of LOAD, using datasets such as ADNI.
  3. Utilize the DIAN cohort and its database and biospecimen repository to support new scientific studies, including use of exome chip technology to examine potential modifiers of age at symptomatic onset, exploratory investigation of new biomarker analytes, imaging modalities and techniques, perform exploratory genetic analysis to test whether novel AD genes identified through GWAS and sequencing of late onset AD cases also influence variation in age at onset of changes in biomarker endophenotypes in FAD kindred, and generate genome-wide DNA methylation data for pilot study and perform exploratory analyses to look for changes in DNA methylation in longitudinal samples from DIAN participants.
  4. Provide genetic counseling to any and all DIAN participants who wish to learn their mutation status and, for those who decide to learn their status after counseling, provide genetic testing by Clinical Laboratory Improvement Amendments (CLIA) - approved laboratories (i.e., outside of DIAN).
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Mutation carriers and non-carriers from families with a mutation (which is different from the genetic risk factor Apo-E4) known to cause Alzheimer's disease.
Criteria

Inclusion Criteria:

  • Written informed consent obtained from participant and collateral source prior to any study-related procedures.
  • Aged 18 (inclusive) or older and the child of an affected individual (clinically or by testing) in a pedigree with a known mutation for ADAD.
  • Cognitively normal. Primary enrollment will focus on recruitment of asymptomatic adult children who are more than 15 years younger than the estimated age of symptom onset. Enrollment of new participants with very mild, mild, or moderate cognitive impairment is allowed with the prior approval of the DIAN Coordinating Center.
  • Has two persons who are not their full-blooded siblings who can serve as collateral sources for the study.
  • Fluent in a language approved by the DIAN Coordinating Center at about the 6th grade level (international equivalent) or above.

Exclusion Criteria:

  • Under age 18
  • Medical or psychiatric illness that would interfere in completing initial and follow-up visits
  • Requires nursing home level care
  • Has no one who can serve as a study informant
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00869817

Contacts
Contact: DIAN Global Coordinator 314-286-2683
Contact: Laura Swisher, BA

Locations
United States, California
University of Southern California Recruiting
Los Angeles, California, United States, 90089-0080
Contact: Lucy Montoya    323-442-2357    Lucy.Montoya@med.usc.edu   
Principal Investigator: Helena Chui, MD         
Sub-Investigator: John Ringman, MD         
United States, Florida
Mayo Clinic Jacksonville Recruiting
Jacksonville, Florida, United States, 32224
Contact: Sochenda Chea, BHA CRC    904-953-3234    chea.sochenda@mayo.edu   
Principal Investigator: Neil R. Graff-Radford, MD         
United States, Indiana
Indiana University-Indiana Alzheimer Disease Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Madeline Cassidy, MS    317-963-7431    mecassid@indiana.edu   
Principal Investigator: Bernardino Ghetti, MD         
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Sehily Jaimes, BA    617-643-5200    sjaimes@partners.org   
Principal Investigator: Jasmeer Chhatwal, MD, PhD         
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63108
Contact: Wendy Sigurdson, RN, MPH    314-362-2256    sigurdsonw@neuro.wustl.edu   
Contact: Tamara Donahue, RN, MS    314-362-2147    donahuet@neuro.wustl.edu   
Principal Investigator: Randall Bateman, MD         
United States, New York
Columbia University Recruiting
New York, New York, United States, 10032
Contact: Dolly Reyes-Dumeyer    212-305-5953    dr2290@cumc.columbia.edu   
Principal Investigator: Richard Mayeux, MD, MSc         
United States, Pennsylvania
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15260
Contact: Zana Ikonomovic, MD    412-692-2740    ikonomovics@upmc.edu   
Principal Investigator: Sarah Berman, MD, PhD         
United States, Rhode Island
Butler Hospital Recruiting
Providence, Rhode Island, United States, 02906
Contact: Courtney Bodge, PhD    401-455-6403    cbodge@butler.org   
Principal Investigator: Stephen Salloway, MD         
Argentina
Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia" (FLENI) Instituto de Investigaciones Neurológicas Raúl Correa Recruiting
Buenos Aires, Argentina
Contact: Patricio Chrem, MD    20565342    pchremmendez@fleni.org.ar   
Principal Investigator: Ricardo Allegri, MD, PhD         
Australia, New South Wales
Neuroscience Research Australia Recruiting
Sydney, New South Wales, Australia, 2031
Contact: William S. Brooks, MBBS, MPH    +612 9399 1101    w.brooks@NeuRA.edu.au   
Principal Investigator: Peter Schofield, PhD, DSc         
Australia, Victoria
Mental Health Research Institute, University of Melbourne Recruiting
Melbourne, Victoria, Australia, 3130
Contact: Lesley Vidaurre, RN    +61 3 8344 1859    lesley.vidaurre@florey.edu.au   
Principal Investigator: Colin Masters, MD         
Australia, Western Australia
Sir James McCusker Alzheimer's Disease Research Unit, Edith Cowan University Recruiting
Perth, Western Australia, Australia, 6009
Contact: Kevin Taddei    +61-(0)8-6304-5107    k.taddei@ecu.edu.au   
Principal Investigator: Ralph Martins, PhD         
Germany
German Center for Neurodegenerative Diseases (DZNE) Munich, and University Hospital Ludwig-Maximilians-Universitat (LMU) Munich Recruiting
Munich, Germany, D-81377
Contact: Siri Houeland di Bari    +49 89 4400 46458    Siri.HouelandDiBari@dzne.de   
Principal Investigator: Johannes Levin, MD, PhD         
German Center for Neurodegenerative Diseases (DZNE) Tübingen and Hertie-Institute for Clinical Brain Research, University of Tübingen Recruiting
Tübingen, Germany, D-72076
Contact: Elke Kuder-Buletta    +49-(0)7071-2987584    Elke.Buletta@med.uni-tuebingen.de   
Principal Investigator: Mathias Jucker, PhD         
Japan
Osaka City University Recruiting
Osaka City, Japan
Contact: Hisako Fujii, PhD    +81-6-6645-3443    hfujii@med.osaka-cu.ac.jp   
Principal Investigator: Hiroyuki Shimada, MD, PhD         
United Kingdom
Institute of Neurology, Queen Square Recruiting
London, United Kingdom, WC1N 3BG
Contact: Jane Douglas, RN MPhil.    0044 (0)845 155 5000 ext 723560    jdouglas@drc.ion.ac.uk   
Principal Investigator: Martin Rossor, MD         
Sponsors and Collaborators
Washington University School of Medicine
National Institute on Aging (NIA)
Investigators
Principal Investigator: Randall J. Bateman, MD Washington University School of Medicine
  More Information

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00869817     History of Changes
Other Study ID Numbers: IA0147  U19AG032438 
Study First Received: March 25, 2009
Last Updated: June 8, 2016
Health Authority: United States: Federal Government

Keywords provided by Washington University School of Medicine:
Alzheimer's disease
antecedent biomarkers
Amyloid Precursor Protein (APP) mutation
presenilin I (PS1) mutation
presenilin 2 (PS2) mutation
Autosomal Dominant Alzheimer's Disease

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

ClinicalTrials.gov processed this record on December 06, 2016