Alzheimers DiseasePhase 2/3DIAN-TUNCT01760005
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
A Phase 2/3 study testing Gantenerumab, Solanezumab and E2814 in people with Alzheimers Disease and Dementia, run by Washington University School of Medicine at 38 sites in 15 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimers Disease, Dementia, Alzheimers Disease, Familial
- What is being tested?
- Gantenerumab, Solanezumab and E2814
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 490 participants
- Where
- 38 sitesin 15 countries
- Study dates
- Dec 2012to Jul 2028
- Phase
- Phase 2/3
- 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 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Show all 9Show fewer
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- 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.
Trial locations and contacts
38 sites in 15 countries.
38 sites in 15 countries
United States12 sites
Emory University
Atlanta, Georgia, 30329
University of Alabama in Birmingham
Birmingham, Alabama, 35294
Kerwin Medical Center
Dallas, Texas, 75231
Indiana University School of Medicine
Indianapolis, Indiana, 46202
University of California San Diego Medical Center
La Jolla, California, 92037
USC Keck School of Medicine
Los Angeles, California, 90033
Yale University School of Medicine
New Haven, Connecticut, 06510
Advocate Lutheran General Hospital
Park Ridge, Illinois, 60068
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Butler Hospital
Providence, Rhode Island, 02096
University of Washington
Seattle, Washington, 98195
Washington University in St. Louis
St Louis, Missouri, 63110
France5 sites
Hopital Neurologique Pierre Wertheimer
Bron, Rhone, 69677
Hopital Roger Salengro - CHU Lille
Lille, Nord, 59037
Groupe Hospitalier Pitie-Salpetriere
Paris, Paris, 69677
CHU de Rouen - Hôpital Charles Nicolle
Rouen, Seine Maritime, 76031
CHU de Toulouse - Hôpital Purpan
Toulouse, Haute Garonne, 31059
Canada4 sites
CHU de Quebec - Hôpital de l' Enfant Jésus
Québec, G1J 1Z4
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
UBC Hospital
Vancouver, British Columbia, V6T 2B5
McGill Center for Studies in Aging
Verdun, Quebec, H4H 1R3
Australia3 sites
Alzheimer's Research Australia
Melbourne, Victoria, 3010
The McCuster Foundation of Alzheimer's Disease Research
Nedlands, Western Australia, 6009
Neuroscience Research Australia
Randwick, New South Wales, 2031
Germany2 sites
LMU-Campus Grosshadern
Munich, Bavaria, 81377
Universitaetsklinikum Tubingen
Tübingen, Baden-Wurttemberg, 72076
Italy2 sites
IRCCS Centro San Giovanni di Dio Fatebenefratelli
Brescia, 25125
Azienda Ospedaliera Universitaria Careggi
Florence, 50134
Japan2 sites
University of Tokyo Hospital
Bunkyō City, Tokyo-To, 113-8655
Niigata University Medical & Dental Hospital
Niigata, Niigata, 951-8520
Argentina1 site
Instituto de Investigaciones Neurologicas Raul Carrea, FLENI
Ciudad Autonoma de Buenos Aire, C1428AQK
Brazil1 site
Hospital das Clínicas da Faculdade de Medicina da USP
São Paulo, 05403-000
Colombia1 site
Grupo de Neurociencias Sede de la Universidad de Antioquia
Medellín
Puerto Rico1 site
University of Puerto Rico, School of Medicine
San Juan, 00936
United Kingdom1 site
The National Hospital for Neurology and Neurosurgery
London, Greater London, WC1B 3BG
About this study
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
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.
Read the 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 was discontinued based on findings from an interim efficacy analysis and the status of the drug program. Primary Completion Date= October 6, 2023; Study final completed visit= November 13, 2023 (NCT06424236)
E2814 treatment arm enrollment complete: Primary Completion Date= April 2028 and Study Completion= July 2028 (NCT05269394)
- Conditions
- Alzheimers Disease, Dementia, Alzheimers Disease, Familial
- Being tested
- Gantenerumab, Solanezumab, Matching Placebo (Gantenerumab), Matching Placebo (Solanezumab), E2814
- Keywords
- 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
- Medical subject headings
- Alzheimer Disease, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GantenerumabDrug
Also called RO4909832
Subcutaneously every 4 weeks at escalating doses
SolanezumabDrug
Also called LY2062430
Intravenous infusion every 4 weeks at escalating doses
Matching Placebo (Gantenerumab)Drug
Subcutaneous injection of placebo every 4 weeks
Matching Placebo (Solanezumab)Drug
Intravenous infusion of placebo every 4 weeks
GantenerumabDrug
Also called RO4909832
Open-label administered Subcutaneously every 4 weeks at escalating doses
E2814Drug
Administered intravenously in a blinded fashion
LecanemabDrug
Also called BAN2401
Administered intravenously
Matching Placebo (E2814)Drug
Placebo administered intravenously in a blinded fashion.
| Study group | Role | What they receive |
|---|---|---|
| Gantenerumab | Experimental | This arm completed and is closed. Receives: Drug: Gantenerumab |
| Solanezumab | Experimental | This arm completed and is closed. Receives: Drug: Solanezumab |
| Matching placebo (Gantenerumab) | Placebo comparator | This arm completed and is closed. Receives: Drug: Matching Placebo (Gantenerumab) |
| Matching Placebo (Solanezumab) | Placebo comparator | This arm completed and is closed. Receives: Drug: Matching Placebo (Solanezumab) |
| Cognitive Run-in | No intervention | This arm is completed and closed. |
| Gantenerumab Open Label Extension | Active comparator | Subcutaneously every 4 weeks at escalating doses. This arm is completed and closed. Receives: Drug: Gantenerumab |
| E2814 plus lecanemab | Experimental | 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. Receives: Drug: E2814; Drug: Lecanemab |
| Matching placebo (E2814) plus lecanemab | Experimental | 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. Receives: Drug: Lecanemab; Drug: Matching Placebo (E2814) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
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)
Measured: Baseline and Weeks 52, 104, 156, and 208
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jan 2013 (estimated)
- Study startDec 2012
- Primary completionApr 2028 (estimated)
- Study completionJul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Alzheimers DiseaseStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Interventional with a non-interventional run-in component (Future interventions to be added)
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 490 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- 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
- Responsible party
- Sponsor
- Investigators
- Randall J Bateman, MD, Study director, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01760005
- Sponsor's protocol ID
- DIAN-TU-001 (Master)
- Other IDs
- The Alzheimer's Association, U01AG042791, 2013-000307-17, R01AG046179, REec-2014-0817, The Alzheimer's Association, GHR Foundation, Alzheimer's Association
- Acronym
- DIAN-TU
- Status last verified
- Jul 2026
- First submitted
- 26 Dec 2012
- Last updated
- 27 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: 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 \[CAP REF\].
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.
PubMed 22784036Farlow 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.
PubMed 22672770Bateman 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.
PubMed 27583651Mills 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.
PubMed 24016464Wang 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.
PubMed 29761523Weninger 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.
PubMed 27157073Grill 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.
PubMed 26203303McDade E, Bateman RJ. Stop Alzheimer's before it starts. Nature. 2017 Jul 12;547(7662):153-155. doi: 10.1038/547153a. No abstract available.
PubMed 28703214McDade 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.
PubMed 30217935Ryman 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.
PubMed 24928124Weng 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.
PubMed 29250611McDade EM, Barthelemy NR, Wang G, Li Y, Cao Y, Gordon B, Benzinger TLS, Clifford D, Goate AM, Renton AE, Hassenstab J, Llibre-Guerra JJ, Perrin RJ, Xiong C, Cruchaga C, Mummery CJ, Berman SB, Lah J, Roberson ED, Van Dyck C, Gauthier S, Masters CL, Masellis M, Bittner T, Yaari R, Chhatwal J, Chrem P, Brooks W, Suzuki K, Levin JJ, Jucker M, Ringman J, Wallon D, Ikeuchi T, Lee JH, Roh JH, Schofield P, Fox NC, Ryan NS, Voglein J, Karch C, Ibanez L, Day GS, Sanchez-Valle R, Daniels A, Morris JC, Supnet-Bell C, Levey AI, Bateman RJ; DIAN-TU Study Team and DIAN Obs Team. The relationship of soluble tau species with Alzheimer's disease amyloid plaque removal and tau pathology. Alzheimers Dement. 2025 Sep;21(9):e70689. doi: 10.1002/alz.70689.
PubMed 40985290Bateman RJ, Li Y, McDade EM, Llibre-Guerra JJ, Clifford DB, Atri A, Mills SL, Santacruz AM, Wang G, Supnet C, Benzinger TLS, Gordon BA, Ibanez L, Klein G, Baudler M, Doody RS, Delmar P, Kerchner GA, Bittner T, Wojtowicz J, Bonni A, Fontoura P, Hofmann C, Kulic L, Hassenstab J, Aschenbrenner AJ, Perrin RJ, Cruchaga C, Renton AE, Xiong C, Goate AA, Morris JC, Holtzman DM, Snider BJ, Mummery C, Brooks WS, Wallon D, Berman SB, Roberson E, Masters CL, Galasko DR, Jayadev S, Sanchez-Valle R, Pariente J, Kinsella J, van Dyck CH, Gauthier S, Hsiung GR, Masellis M, Dubois B, Honig LS, Jack CR, Daniels A, Aguillon D, Allegri R, Chhatwal J, Day G, Fox NC, Huey E, Ikeuchi T, Jucker M, Lee JH, Levey AI, Levin J, Lopera F, Roh J, Rosa-Neto P, Schofield PR; Dominantly Inherited Alzheimer's Disease-Trials Unit. Safety and efficacy of long-term gantenerumab treatment in dominantly inherited Alzheimer's disease: an open-label extension of the phase 2/3 multicentre, randomised, double-blind, placebo-controlled platform DIAN-TU trial. Lancet Neurol. 2025 Apr;24(4):316-330. doi: 10.1016/S1474-4422(25)00024-9.
PubMed 40120616Bateman RJ, Li Y, McDade EM, Llibre-Guerra JJ, Clifford DB, Atri A, Mills SL, Santacruz AM, Wang G, Supnet C, Benzinger TLS, Gordon BA, Ibanez L, Klein G, Baudler M, Doody RS, Delmar P, Kerchner GA, Bittner T, Wojtowicz J, Bonni A, Fontoura P, Hofmann C, Kulic L, Hassenstab J, Aschenbrenner AJ, Perrin RJ, Cruchaga C, Renton AE, Xiong C, Goate AA, Morris JC, Holtzman DM, Snider BJ, Mummery C, Brooks WS, Wallon D, Berman SB, Roberson E, Masters CL, Galasko DR, Jayadev S, Sanchez-Valle R, Pariente J, Kinsella J, van Dyck CH, Gauthier S, Robin Hsiung GY, Masellis M, Dubois B, Honig LS, Jack CR, Daniels A, Aguillon D, Allegri R, Chhatwal J, Day G, Fox N, Huey E, Ikeuchi T, Jucker M, Lee JH, Levey AI, Levin J, Lopera F, Roh J, Rosa-Neto P, Schofield PR; Dominantly Inherited Alzheimer's Disease-Trials Unit. Safety and efficacy of long-term gantenerumab treatment in dominantly inherited Alzheimer's disease: an open label extension of the phase 2/3 multicentre, randomised, double-blind, placebo-controlled platform DIAN-TU Trial. medRxiv [Preprint]. 2025 Jan 29:2024.10.29.24316289. doi: 10.1101/2024.10.29.24316289.
PubMed 39974075Chen CD, McCullough A, Gordon B, Joseph-Mathurin N, Flores S, McKay NS, Hobbs DA, Hornbeck R, Fagan AM, Cruchaga C, Goate AM, Perrin RJ, Wang G, Li Y, Shi X, Xiong C, Pontecorvo MJ, Klein G, Su Y, Klunk WE, Jack C, Koeppe R, Snider BJ, Berman SB, Roberson ED, Brosch J, Surti G, Jimenez-Velazquez IZ, Galasko D, Honig LS, Brooks WS, Clarnette R, Wallon D, Dubois B, Pariente J, Pasquier F, Sanchez-Valle R, Shcherbinin S, Higgins I, Tunali I, Masters CL, van Dyck CH, Masellis M, Hsiung R, Gauthier S, Salloway S, Clifford DB, Mills S, Supnet-Bell C, McDade E, Bateman RJ, Benzinger TLS; DIAN-TU Study Team. Longitudinal head-to-head comparison of 11C-PiB and 18F-florbetapir PET in a Phase 2/3 clinical trial of anti-amyloid-beta monoclonal antibodies in dominantly inherited Alzheimer's disease. Eur J Nucl Med Mol Imaging. 2023 Jul;50(9):2669-2682. doi: 10.1007/s00259-023-06209-0. Epub 2023 Apr 5.
PubMed 37017737
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01760005
- Acronym / sponsor ID
- DIAN-TU / DIAN-TU-001 (Master)
- Conditions
- Alzheimers Disease, Dementia, Alzheimers Disease, Familial
- Keywords
- Alzheimer's, Alzheimer's Disease, Dementia, Mutation, Genetic Mutation, Dominantly Inherited Alzheimer's Disease, Dominantly Inherited Alzheimer Network, Autosomal Dominant Alzheimer's Disease
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 490 participants (estimated)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- 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
- Study start
- Dec 2012 (actual)
- Primary completion
- Apr 2028 (estimated)
- Study completion
- Jul 2028 (estimated)
- First posted
- 3 Jan 2013 (estimated)
- 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.
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.
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 was discontinued based on findings from an interim efficacy analysis and the status of the drug program. Primary Completion Date= October 6, 2023; Study final completed visit= November 13, 2023 (NCT06424236)
E2814 treatment arm enrollment complete: Primary Completion Date= April 2028 and Study Completion= July 2028 (NCT05269394)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 8
- Model description
- Interventional with a non-interventional run-in component (Future interventions to be added)
| Arm | Type | Receives |
|---|---|---|
| Gantenerumab | Experimental | Drug: GantenerumabThis arm completed and is closed. |
| Solanezumab | Experimental | Drug: SolanezumabThis arm completed and is closed. |
| Matching placebo (Gantenerumab) | Placebo comparator | Drug: Matching Placebo (Gantenerumab)This arm completed and is closed. |
| Matching Placebo (Solanezumab) | Placebo comparator | Drug: Matching Placebo (Solanezumab)This arm completed and is closed. |
| Cognitive Run-in | No intervention | –This arm is completed and closed. |
| Gantenerumab Open Label Extension | Active comparator | Drug: GantenerumabSubcutaneously every 4 weeks at escalating doses. This arm is completed and closed. |
| E2814 plus lecanemab | Experimental | Drug: E2814, Drug: LecanemabSymptomatic 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. |
| Matching placebo (E2814) plus lecanemab | Experimental | Drug: Lecanemab, Drug: Matching Placebo (E2814)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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GantenerumabAlso: RO4909832Subcutaneously every 4 weeks at escalating doses | Drug | Gantenerumab |
| SolanezumabAlso: LY2062430Intravenous infusion every 4 weeks at escalating doses | Drug | Solanezumab |
| Matching Placebo (Gantenerumab)Subcutaneous injection of placebo every 4 weeks | Drug | Matching placebo (Gantenerumab) |
| Matching Placebo (Solanezumab)Intravenous infusion of placebo every 4 weeks | Drug | Matching Placebo (Solanezumab) |
| GantenerumabAlso: RO4909832Open-label administered Subcutaneously every 4 weeks at escalating doses | Drug | Gantenerumab Open Label Extension |
| E2814Administered intravenously in a blinded fashion | Drug | E2814 plus lecanemab |
| LecanemabAlso: BAN2401Administered intravenously | Drug | E2814 plus lecanemab, Matching placebo (E2814) plus lecanemab |
| Matching Placebo (E2814)Placebo administered intravenously in a blinded fashion. | Drug | Matching placebo (E2814) plus lecanemab |
Primary outcome
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)
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 27 Jul 2026.
- Background: PubMed 22784036Bateman 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.
- Background: PubMed 22672770Farlow 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.
- Background: PubMed 27583651Bateman 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.
- Background: PubMed 24016464Mills 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.
- Background: PubMed 29761523Wang 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.
- Background: PubMed 27157073Weninger 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.
- Background: PubMed 26203303Grill 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.
- Background: PubMed 28703214McDade E, Bateman RJ. Stop Alzheimer's before it starts. Nature. 2017 Jul 12;547(7662):153-155. doi: 10.1038/547153a. No abstract available.
- Background: PubMed 30217935McDade 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.
- Background: PubMed 24928124Ryman 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.
- Background: PubMed 29250611Weng 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.
- Derived from this study: PubMed 40985290McDade EM, Barthelemy NR, Wang G, Li Y, Cao Y, Gordon B, Benzinger TLS, Clifford D, Goate AM, Renton AE, Hassenstab J, Llibre-Guerra JJ, Perrin RJ, Xiong C, Cruchaga C, Mummery CJ, Berman SB, Lah J, Roberson ED, Van Dyck C, Gauthier S, Masters CL, Masellis M, Bittner T, Yaari R, Chhatwal J, Chrem P, Brooks W, Suzuki K, Levin JJ, Jucker M, Ringman J, Wallon D, Ikeuchi T, Lee JH, Roh JH, Schofield P, Fox NC, Ryan NS, Voglein J, Karch C, Ibanez L, Day GS, Sanchez-Valle R, Daniels A, Morris JC, Supnet-Bell C, Levey AI, Bateman RJ; DIAN-TU Study Team and DIAN Obs Team. The relationship of soluble tau species with Alzheimer's disease amyloid plaque removal and tau pathology. Alzheimers Dement. 2025 Sep;21(9):e70689. doi: 10.1002/alz.70689.
- Expanded registryLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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].
Related trials for Alzheimers Disease
RecruitingPhase 2
Neuroplasticity Enhancement From Cognitive Training Reinforced by Psilocybin
Alzheimer's Disease
Not yet recruiting
Acupressure as Long-term Intervention to Slow the Progression of Early/Mild Alzheimer's Disease
Alzheimer's Disease
RecruitingObservational study
Effectiveness and Safety of Disease-Modifying Therapy for Alzheimer's Disease: A Multicenter Retrospective Study
Alzheimer's Disease (AD)
RecruitingPhase 3
A Phase 3 Study to Evaluate the Safety and Efficacy of KarXT + KarX-EC for the Treatment of Agitation Associated With Alzheimer's Disease (ADAGIO-1)
Alzheimer Disease
RecruitingPhase 3
A Study of Trontinemab in Cognitively Unimpaired Individuals at Risk for Progression to Symptomatic Alzheimer's Disease
Alzheimer's Disease
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. This study is not recruiting at the moment.
Randall J Bateman, MD study director
Washington University School of Medicine
38 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Gantenerumab, Solanezumab and E2814 in people with Alzheimers Disease and Dementia, run by Washington University School of Medicine at 38 sites in 15 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 9 inclusion and 9 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: under way, not looking for participants, as of the sponsor's last update on 27 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in United States, France, Canada, Australia, Germany and 10 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
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?
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). 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 NCT01760005, which also lists 15 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 27 Jul 2026.