Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation. Master Protocol DIAN-TU-001 (DIAN-TU)

• ClinicalTrials.gov Identifier: NCT01760005
• Recruitment Status: Recruiting
• First Posted: January 3, 2013
• Last Update Posted: May 12, 2023
• Sponsor: Washington University School of Medicine
• Collaborators: Eli Lilly and Company; Hoffmann-La Roche; Alzheimer's Association; National Institute on Aging (NIA); Avid Radiopharmaceuticals; Accelerating Medicines Partnership (AMP); Eisai Inc.; Janssen, LP
• Information provided by (Responsible Party): Washington University School of Medicine

Study Description

Brief Summary:

The purpose of this study is to assess the safety, tolerability, biomarker, cognitive and clinical efficacy of investigational products in participants with an Alzheimer's disease-causing mutation by determining if treatment with the study drug slows the rate of progression of cognitive/clinical impairment or improves disease-related biomarkers.

Condition or disease	Intervention/treatment	Phase
Alzheimers Disease; Dementia; Alzheimers Disease, Familial	Drug: Gantenerumab; Drug: Solanezumab; Drug: Matching Placebo (Gantenerumab); Drug: Matching Placebo (Solanezumab); Drug: E2814; Drug: Lecanemab; Drug: Matching Placebo (E2814)	Phase 2; Phase 3

Detailed Description:

This study will recruit participants from the Dominantly Inherited Alzheimer Network (DIAN) observational study, a multicenter international study supported by the National Institutes of Health (Grant Number U01-AG032438; RJ Bateman), Dominantly Inherited Alzheimer Network Trial Units (DIAN-TU) sites, DIAN-TU partner sites, DIAN Expanded Registry (DIAN-EXR), and families identified by the sites. As part of the DIAN-TU-001 protocol, participants undergo longitudinal assessments that include clinical assessment, cognitive testing, magnetic resonance imaging (MRI) and amyloid and tau positron emission tomography (PET) imaging, and analysis of blood and cerebrospinal fluid (CSF).

Participants in DIAN are recruited from families that have at least one member who has been identified as having a mutation linked to dominantly inherited Alzheimer's disease (DIAD). The mutations in presenilin 1 (PSEN1), presenilin 2 (PSEN2) and amyloid precursor protein (APP) that are associated with dominantly inherited Alzheimer's disease have very high penetrance (near 100%). This study enrolls individuals who are either known to have a disease-causing mutation or who are at risk for such a mutation (the descendant or sibling of a proband with a known mutation) and unaware of their genetic status. Because the age at onset of cognitive changes is relatively consistent within each family and with each mutation, an age at onset is determined for each affected parent or mutation as part of the DIAN Observational (DIAN-OBS) study protocol. This study will enroll participants who are either asymptomatic and are within a specific window of time of expected age at onset for their family and/or mutation or who have symptoms of mild Alzheimer's disease.

The ability to identify individuals destined to develop Alzheimer's disease (AD) and predict the age of onset with a high degree of confidence provides a unique opportunity to assess the efficacy of therapies at asymptomatic and very early stages of dementia. Families with known disease-causing mutations are extremely rare and are geographically dispersed throughout the world. These constraints necessitate a specialized study design. Many of the participants in this study will not yet have any cognitive symptoms of AD; they will be "asymptomatic" carriers of mutations that cause dominantly inherited Alzheimer's disease and would be expected to perform normally on standard cognitive and functional testing. Imaging and fluid biomarkers will be used to demonstrate that the treatment compounds have engaged their therapeutic targets. A set of cognitive measures designed to assess the very earliest and most subtle cognitive changes will be collected. Additionally, because many at-risk individuals decide not to know whether they have the disease-associated mutation or not, when allowable in individual drug arms, some of the at-risk individuals enrolled in this study will not have the disease-causing mutations; they will be "mutation negative". It is important to enroll these participants to avoid coercion (e.g., potential participants may be pressured into genetic testing to learn their genetic status in order to be eligible for the trial) unless the drug-specific design includes open-label treatment. These mutation negative individuals will be assigned to the placebo group and data will be used to determine normal ranges of outcome measures. Participants and site study staff will remain blinded as to these individuals' active or placebo group assignment and mutation status. Thus, the study will be double-blinded for placebo and for mutation status, except for mutation positive participants who are aware of their genetic status. There may be exceptional circumstances when required by local regulation or health authorities where enrollment may be restricted to mutation carriers only, but such mandates will be thoroughly documented and agreed upon by the governing regulatory agency and sponsor.

This is an adaptive platform-based study. Several different therapies (each referred to as a study drug arm) will be tested in order to increase the likelihood that an effective treatment will be discovered. The compounds are selected for this trial based on mechanism of action and available data on efficacy and safety profile. The study design includes a pooled placebo group (referred to as the mutation positive placebos) which may be shared by study drug arms. Mutation positive participants will be assigned to a study drug arm and subsequently randomized within that arm to the active drug to placebo ratio specified in each drug-specific appendix. When included in individual drug arms, mutation negative participants will all receive placebo treatment. Participants and study staff will not be blinded as to which study drug arm each participant has been assigned; they will be blinded as to whether participants have been randomized to active drug or placebo.

Biomarker, cognitive, and/or clinical endpoints will be specified for each study drug arm. Biomarker data will be analyzed for pre-specified endpoints consistent with the drug's mechanism of action and other AD biomarker outcomes.

Interim analyses of the imaging or fluid biomarker endpoint will assess safety and whether each study drug engages its biological targets. The clinical and cognitive assessments are designed to assess subtle cognitive changes that may be detectable before the onset of dementia as well as cognitive and clinical decline in symptomatic groups.

After the last participant in a study drug arm completes the 4-year treatment period, participants in that study drug arm may be eligible to receive active study drug in an open-label extension period.

A cognitive run-in (CRI) period was implemented to allow for enrollment during periods when study drug arms are not randomizing. This enables the DIAN-TU platform to have continuous enrollment during periods before or in-between drug arm randomization.

The CRI period of cognitive, clinical, and imaging data collection was designed as part of the platform study to utilize the time in between enrollment of study drug arms. The CRI period will enhance study enrollment by identifying eligible participants and engaging them with the cognitive assessments and can reduce practice effects by allowing participants to habituate to the testing process. The CRI further provides important baseline and run-in data that adds control data to the platform and informs about the effects of tested drugs. The data collected in the CRI period will be used for analysis in the respective drug arm under which participants are randomized and treated.

Solanezumab and gantenerumab double blind treatment arms: Primary Completion Date= Nov 2019 and Study Completion= March 2020 (NCT04623242)

Gantenerumab open-label extension is enrolling by invitation under this master protocol. Primary Completion Date= Sept 2024

E2814 treatment arm is enrolling: Primary Completion Date= July 2027 and Study Completion= Oct 2027 (NCT05269394)

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 490 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Interventional with a non-interventional run-in component (Future interventions to be added)
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: One arm is Open-label as noted in the arm descriptions
• Primary Purpose: Treatment
• Official Title: A Phase II/III Multicenter Randomized, Double-Blind, Placebo-Controlled Platform Trial of Potential Disease Modifying Therapies Utilizing Biomarker, Cognitive, and Clinical Endpoints in Dominantly Inherited Alzheimer's Disease
• Actual Study Start Date: December 2012
• Estimated Primary Completion Date: October 2027
• Estimated Study Completion Date: October 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: Gantenerumab; This arm completed and is closed.	Drug: Gantenerumab; Subcutaneously every 4 weeks at escalating doses; Other Name: RO4909832
Experimental: Solanezumab; This arm completed and is closed.	Drug: Solanezumab; Intravenous infusion every 4 weeks at escalating doses; Other Name: LY2062430
Placebo Comparator: Matching placebo (Gantenerumab); This arm completed and is closed.	Drug: Matching Placebo (Gantenerumab); Subcutaneous injection of placebo every 4 weeks
Placebo Comparator: Matching Placebo (Solanezumab); This arm completed and is closed.	Drug: Matching Placebo (Solanezumab); Intravenous infusion of placebo every 4 weeks
No Intervention: Cognitive Run-in
Active Comparator: Gantenerumab Open Label Extension; Subcutaneously every 4 weeks at escalating doses	Drug: Gantenerumab; Open-label administered Subcutaneously every 4 weeks at escalating doses; Other Name: RO4909832
Experimental: E2814 plus lecanemab; Symptomatic Population (Cohort 1) At Week 0, participants will receive open-label lecanemab administered intravenously for the full treatment period. At Week 24, participants randomized to E2814 will receive intravenously in a blinded fashion for the remainder of their treatment period. Asymptomatic Population (Cohort 2) At Week 0, participants randomized to E2814 will receive intravenously in a blinded fashion for the full treatment period. At Week 52, all participants will initiate open-label lecanemab administered intravenously for the remainder of their treatment period.	Drug: E2814; Administered intravenously in a blinded fashion; Drug: Lecanemab; Administered intravenously; Other Name: BAN2401
Experimental: Matching placebo (E2814) plus lecanemab; Symptomatic Population (Cohort 1) At Week 0, participants will receive open-label lecanemab administered intravenously for the full treatment period. At Week 24, participants randomized to E2814 placebo will receive placebo intravenously in a blinded fashion for the remainder of their treatment period. Asymptomatic Population (Cohort 2) At Week 0, participants randomized to E2814 placebo will receive placebo intravenously in a blinded fashion for the full treatment period. At Week 52, all participants will initiate open-label lecanemab administered intravenously for the remainder of their treatment period.	Drug: Lecanemab; Administered intravenously; Other Name: BAN2401; Drug: Matching Placebo (E2814); Placebo administered intravenously in a blinded fashion.

Outcome Measures

Primary Outcome Measures :

1. Assess cognitive efficacy in individuals with mutations causing dominantly inherited AD as measured by the change from baseline in the DIAN-Multivariate Cognitive Endpoint (DIAN-MCE) [ Time Frame: Baseline and Weeks 52, 104, 156, and 208 ]
   The DIAN-Multivariate Cognitive Endpoint (DIAN-MCE) consists of 4 cognitive measures: Wechsler Memory Scale-Revised Logical Memory Delayed Recall Test, Wechsler Adult Intelligence Sale Digit Symbol Substitution Test (WAIS), International Shopping List Task (ISLT), Mini-Mental State Examination (MMSE)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Between 18-80 years of age
• Individuals who know they have an Alzheimer's disease-causing mutation or are unaware of their genetic status and have dominantly inherited Alzheimer's disease (DIAD) mutation in their family.
• Are within -15 to + 10 years of the predicted or actual age of cognitive symptom onset. For Cognitive Run-In (CRI): includes participants who are younger than 15 years prior to the expected age of cognitive symptom onset, in addition to those 15 years younger and no more than 10 years older than expected or actual age of cognitive symptom onset.
• Cognitively normal or with mild cognitive impairment or mild dementia, Clinical Dementia Rating (CDR) of 0-1 (inclusive)
• Fluency in DIAN-TU trial approved language and evidence of adequate premorbid intellectual functioning
• Able to undergo Magnetic Resonance Imaging (MRI), Lumbar Puncture (LP), Positron Emission Tomography (PET), and complete all study related testing and evaluations.
• For women of childbearing potential, if partner is not sterilized, subject must agree to use effective contraceptive measures (hormonal contraception, intra-uterine device, sexual abstinence, barrier method with spermicide).
• Adequate visual and auditory abilities to perform all aspects of the cognitive and functional assessments.
• Has a Study Partner who in the investigator's judgment is able to provide accurate information as to the subject's cognitive and functional abilities, who agrees to provide information at the study visits which require informant input for scale completion.

Exclusion Criteria:

• History or presence of brain MRI scans indicative of any other significant abnormality
• Alcohol or drug dependence currently or within the past 1 year
• Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, or foreign metal objects in the eyes, skin or body which would preclude MRI scan.
• History or presence of clinically significant cardiovascular disease, hepatic/renal disorders, infectious disease or immune disorder, or metabolic/endocrine disorders
• Anticoagulants except low dose (≤ 325 mg) aspirin.
• Have been exposed to a monoclonal antibody targeting beta amyloid peptide within the past six months.
• History of cancer within the last 5 years, except basal cell carcinoma, non-squamous skin carcinoma, prostate cancer or carcinoma in situ with no significant progression over the past 2 years.
• Positive urine or serum pregnancy test or plans or desires to become pregnant during the course of the trial.
• Subjects unable to complete all study related testing, including implanted metal that cannot be removed for MRI scanning, required anticoagulation and pregnancy.

Contacts and Locations

Contacts

Contact: Ellen Ziegemeier, MA; 844-DIANEXR (342-6397); dianexr@wustl.edu

Contact: Jamie Bartzel; 844-DIANEXR (342-6397); dianexr@wustl.edu

Locations

United States, Alabama

University of Alabama in Birmingham; Recruiting

Birmingham, Alabama, United States, 35294

Principal Investigator: Erik Roberson

United States, California

University of California San Diego Medical Center; Recruiting

La Jolla, California, United States, 92037

Principal Investigator: Doug Galasko

USC Keck School of Medicine; Not yet recruiting

Los Angeles, California, United States, 90033

Principal Investigator: Sonia Pawluczyk

United States, Connecticut

Yale University School of Medicine; Active, not recruiting

New Haven, Connecticut, United States, 06510

United States, Georgia

Emory University; Recruiting

Atlanta, Georgia, United States, 30329

Principal Investigator: James Lah

United States, Illinois

Advocate Lutheran General Hospital; Recruiting

Park Ridge, Illinois, United States, 60068

Principal Investigator: Darren Gitelman

United States, Indiana

Indiana University School of Medicine; Recruiting

Indianapolis, Indiana, United States, 46202

Principal Investigator: Jared Brosch

United States, Missouri

Washington University in St. Louis; Recruiting

Saint Louis, Missouri, United States, 63110

Principal Investigator: Barbara Snider

United States, Pennsylvania

University of Pittsburgh; Recruiting

Pittsburgh, Pennsylvania, United States, 15213

Principal Investigator: Sarah Berman

United States, Rhode Island

Butler Hospital; Recruiting

Providence, Rhode Island, United States, 02096

Principal Investigator: Ghulam Surti

United States, Texas

Kerwin Medical Center; Recruiting

Dallas, Texas, United States, 75231

Principal Investigator: Diana Kerwin

United States, Washington

University of Washington; Recruiting

Seattle, Washington, United States, 98195

Principal Investigator: Suman Jayadev

Argentina

Instituto de Investigaciones Neurologicas Raul Carrea, FLENI; Recruiting

Ciudad Autonoma de Buenos Aire, Argentina, C1428AQK

Principal Investigator: Ricardo Allegri

Australia, New South Wales

Neuroscience Research Australia; Recruiting

Randwick, New South Wales, Australia, 2031

Principal Investigator: William Brooks

Australia, Victoria

Mental Health Research Institute; Recruiting

Melbourne, Victoria, Australia, 3010

Principal Investigator: Colin Masters

Australia, Western Australia

The McCuster Foundation of Alzheimer's Disease Research; Active, not recruiting

Nedlands, Western Australia, Australia, 6009

Brazil

Hospital das Clínicas da Faculdade de Medicina da USP; Not yet recruiting

São Paulo, Brazil, 05403-000

Principal Investigator: Leonel Takada

Canada, British Columbia

UBC Hospital; Recruiting

Vancouver, British Columbia, Canada, V6T 2B5

Principal Investigator: Robin Hsiung

Canada, Ontario

Sunnybrook Health Sciences Centre; Recruiting

Toronto, Ontario, Canada, M4N 3M5

Principal Investigator: Mario Masellis

Canada, Quebec

McGill Center for Studies in Aging; Recruiting

Verdun, Quebec, Canada, H4H 1R3

Principal Investigator: Pedro Rosa-Neto

Canada

CHU de Quebec - Hôpital de l' Enfant Jésus; Not yet recruiting

Québec, Canada, G1J 1Z4

Principal Investigator: Robert LaForce

Colombia

Grupo de Neurociencias Sede de la Universidad de Antioquia; Recruiting

Medellín, Colombia

Principal Investigator: Francisco Lopera, M.D.

France

CHU de Toulouse - Hôpital Purpan; Recruiting

Toulouse, Haute Garonne, France, 31059

Principal Investigator: Jérémie Pariente

Hopital Roger Salengro - CHU Lille; Recruiting

Lille, Nord, France, 59037

Principal Investigator: Florence Pasquier

Groupe Hospitalier Pitie-Salpetriere; Recruiting

Paris cedex 13, Paris, France, 69677

Principal Investigator: Richard Levy

Hopital Neurologique Pierre Wertheimer; Recruiting

Bron cedex, Rhone, France, 69677

Principal Investigator: Maité Formaglio

CHU de Rouen - Hôpital Charles Nicolle; Recruiting

Rouen, Seine Maritime, France, 76031

Principal Investigator: David Wallon

Germany

Universitaetsklinikum Tubingen; Not yet recruiting

Tübingen, Baden Wuerttemberg, Germany, 72076

Principal Investigator: Cristoph Laske, M.D.

LMU-Campus Grosshadern; Not yet recruiting

Muenchen, Bayern, Germany, 81377

Principal Investigator: Johannes Levin, M.D,

Ireland

St Vincent's University Hospital; Recruiting

Dublin, Ireland, DUBLIN 4

Principal Investigator: Justin Kinsella

Italy

IRCCS Centro San Giovanni di Dio Fatebenefratelli; Not yet recruiting

Brescia, Italy, 25125

Principal Investigator: Giovanni Frisoni, M.D,

Azienda Ospedaliera Universitaria Careggi; Not yet recruiting

Firenze, Italy, 50134

Principal Investigator: Sandro Sorbi, M.D.

Japan

University of Tokyo Hospital; Not yet recruiting

Bunkyō-Ku, Tokyo-To, Japan, 113-8655

Principal Investigator: Ryoko Ihara, M.D.

Mexico

Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez; Not yet recruiting

Mexico, Distrito Federal, Mexico, 14269

Principal Investigator: Ana Luisa Sosa Ortiz, M.D.

Netherlands

Brain Research Center; Recruiting

Amsterdam, Netherlands, 1081 GM

Principal Investigator: Jort Vijverberg, MD

Puerto Rico

University of Puerto Rico, School of Medicine; Recruiting

San Juan, Puerto Rico, 00936

Principal Investigator: Ivonne Jimenez-Velazquez

Spain

Hospital Clínic I Provincial de Barcelona; Recruiting

Barcelona, Spain, 8036

Principal Investigator: Raquel Sanchez Valle

United Kingdom

The National Hospital for Neurology and Neurosurgery; Recruiting

London, Greater London, United Kingdom, WC1B 3BG

Principal Investigator: Catherine Mummery

Sponsors and Collaborators

Washington University School of Medicine

Eli Lilly and Company

Hoffmann-La Roche

Alzheimer's Association

National Institute on Aging (NIA)

Avid Radiopharmaceuticals

Accelerating Medicines Partnership (AMP)

Eisai Inc.

Janssen, LP

Investigators

• Study Director: Randall J Bateman, MD; Washington University School of Medicine

More Information

Additional Information:

Expanded registry 

Publications:

Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, Marcus DS, Cairns NJ, Xie X, Blazey TM, Holtzman DM, Santacruz A, Buckles V, Oliver A, Moulder K, Aisen PS, Ghetti B, Klunk WE, McDade E, Martins RN, Masters CL, Mayeux R, Ringman JM, Rossor MN, Schofield PR, Sperling RA, Salloway S, Morris JC; Dominantly Inherited Alzheimer Network. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med. 2012 Aug 30;367(9):795-804. doi: 10.1056/NEJMoa1202753. Epub 2012 Jul 11. Erratum In: N Engl J Med. 2012 Aug 23;367(8):780.

Farlow M, Arnold SE, van Dyck CH, Aisen PS, Snider BJ, Porsteinsson AP, Friedrich S, Dean RA, Gonzales C, Sethuraman G, DeMattos RB, Mohs R, Paul SM, Siemers ER. Safety and biomarker effects of solanezumab in patients with Alzheimer's disease. Alzheimers Dement. 2012 Jul;8(4):261-71. doi: 10.1016/j.jalz.2011.09.224. Epub 2012 Jun 5.

Bateman RJ, Benzinger TL, Berry S, Clifford DB, Duggan C, Fagan AM, Fanning K, Farlow MR, Hassenstab J, McDade EM, Mills S, Paumier K, Quintana M, Salloway SP, Santacruz A, Schneider LS, Wang G, Xiong C; DIAN-TU Pharma Consortium for the Dominantly Inherited Alzheimer Network. The DIAN-TU Next Generation Alzheimer's prevention trial: Adaptive design and disease progression model. Alzheimers Dement. 2017 Jan;13(1):8-19. doi: 10.1016/j.jalz.2016.07.005. Epub 2016 Aug 29.

Mills SM, Mallmann J, Santacruz AM, Fuqua A, Carril M, Aisen PS, Althage MC, Belyew S, Benzinger TL, Brooks WS, Buckles VD, Cairns NJ, Clifford D, Danek A, Fagan AM, Farlow M, Fox N, Ghetti B, Goate AM, Heinrichs D, Hornbeck R, Jack C, Jucker M, Klunk WE, Marcus DS, Martins RN, Masters CM, Mayeux R, McDade E, Morris JC, Oliver A, Ringman JM, Rossor MN, Salloway S, Schofield PR, Snider J, Snyder P, Sperling RA, Stewart C, Thomas RG, Xiong C, Bateman RJ. Preclinical trials in autosomal dominant AD: implementation of the DIAN-TU trial. Rev Neurol (Paris). 2013 Oct;169(10):737-43. doi: 10.1016/j.neurol.2013.07.017. Epub 2013 Sep 6.

Wang G, Berry S, Xiong C, Hassenstab J, Quintana M, McDade EM, Delmar P, Vestrucci M, Sethuraman G, Bateman RJ; Dominantly Inherited Alzheimer Network Trials Unit. A novel cognitive disease progression model for clinical trials in autosomal-dominant Alzheimer's disease. Stat Med. 2018 Sep 20;37(21):3047-3055. doi: 10.1002/sim.7811. Epub 2018 May 14.

Weninger S, Carrillo MC, Dunn B, Aisen PS, Bateman RJ, Kotz JD, Langbaum JB, Mills SL, Reiman EM, Sperling R, Santacruz AM, Tariot PN, Welsh-Bohmer KA. Collaboration for Alzheimer's Prevention: Principles to guide data and sample sharing in preclinical Alzheimer's disease trials. Alzheimers Dement. 2016 May;12(5):631-2. doi: 10.1016/j.jalz.2016.04.001. No abstract available.

Grill JD, Bateman RJ, Buckles V, Oliver A, Morris JC, Masters CL, Klunk WE, Ringman JM; Dominantly Inherited Alzheimer's Network. A survey of attitudes toward clinical trials and genetic disclosure in autosomal dominant Alzheimer's disease. Alzheimers Res Ther. 2015 Jul 22;7(1):50. doi: 10.1186/s13195-015-0135-0. eCollection 2015.

McDade E, Bateman RJ. Stop Alzheimer's before it starts. Nature. 2017 Jul 12;547(7662):153-155. doi: 10.1038/547153a. No abstract available.

McDade E, Wang G, Gordon BA, Hassenstab J, Benzinger TLS, Buckles V, Fagan AM, Holtzman DM, Cairns NJ, Goate AM, Marcus DS, Morris JC, Paumier K, Xiong C, Allegri R, Berman SB, Klunk W, Noble J, Ringman J, Ghetti B, Farlow M, Sperling RA, Chhatwal J, Salloway S, Graff-Radford NR, Schofield PR, Masters C, Rossor MN, Fox NC, Levin J, Jucker M, Bateman RJ; Dominantly Inherited Alzheimer Network. Longitudinal cognitive and biomarker changes in dominantly inherited Alzheimer disease. Neurology. 2018 Oct 2;91(14):e1295-e1306. doi: 10.1212/WNL.0000000000006277. Epub 2018 Sep 14.

Ryman DC, Acosta-Baena N, Aisen PS, Bird T, Danek A, Fox NC, Goate A, Frommelt P, Ghetti B, Langbaum JB, Lopera F, Martins R, Masters CL, Mayeux RP, McDade E, Moreno S, Reiman EM, Ringman JM, Salloway S, Schofield PR, Sperling R, Tariot PN, Xiong C, Morris JC, Bateman RJ; Dominantly Inherited Alzheimer Network. Symptom onset in autosomal dominant Alzheimer disease: a systematic review and meta-analysis. Neurology. 2014 Jul 15;83(3):253-60. doi: 10.1212/WNL.0000000000000596. Epub 2014 Jun 13.

Weng H, Bateman R, Morris JC, Xiong C. Validity and power of minimization algorithm in longitudinal analysis of clinical trials. Biostat Epidemiol. 2017;1(1):59-77. doi: 10.1080/24709360.2017.1331822. Epub 2017 Jun 13.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT01760005
• Other Study ID Numbers: DIAN-TU-001 (Master); The Alzheimer's Association ( Other Grant/Funding Number: DIAN TTU-12-243040 ); U01AG042791 ( U.S. NIH Grant/Contract ); 2013-000307-17 ( EudraCT Number ); R01AG046179 ( U.S. NIH Grant/Contract ); REec-2014-0817 ( Registry Identifier: Spanish Clinical Studies Registry ); The Alzheimer's Association ( Other Grant/Funding Number: DIAN-TU Tau-15-347219 ); GHR Foundation ( Other Grant/Funding Number: File 4401 ); Alzheimer's Association ( Other Identifier: HDE 18S84914 ); The Alzheimer's Association ( Other Grant/Funding Number: DIAN-TU NG-16-434362 ); R56AG053267 ( U.S. NIH Grant/Contract ); U01AG059798 ( U.S. NIH Grant/Contract ); R01AG053267 ( U.S. NIH Grant/Contract )
• First Posted: January 3, 2013
• Last Update Posted: May 12, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Access to DIAN-TU trial data will follow the DIAN-TU data access policy, which complies with the guidelines established by the Collaboration for Alzheimer's Prevention [CAP REF].

Keywords provided by Washington University School of Medicine:

Alzheimer's; Alzheimer's Disease; Dementia; Mutation; Genetic Mutation; Dominantly Inherited Alzheimer's Disease; Dominantly Inherited Alzheimer Network; Autosomal Dominant Alzheimer's Disease; Early Onset Alzheimer's Disease; DIAN; DIAN-TU; DIAN TU; DIAD

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs