Dementia Clinical Trial
— DIAN-TUOfficial 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.
Status | Recruiting |
Enrollment | 490 |
Est. completion date | October 2027 |
Est. primary completion date | October 2027 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 80 Years |
Eligibility | 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. |
Country | Name | City | State |
---|---|---|---|
Argentina | Instituto de Investigaciones Neurologicas Raul Carrea, FLENI | Ciudad Autonoma de Buenos Aire | |
Australia | Mental Health Research Institute | Melbourne | Victoria |
Australia | The McCuster Foundation of Alzheimer's Disease Research | Nedlands | Western Australia |
Australia | Neuroscience Research Australia | Randwick | New South Wales |
Brazil | Hospital das Clínicas da Faculdade de Medicina da USP | São Paulo | |
Canada | CHU de Quebec - Hôpital de l' Enfant Jésus | Québec | |
Canada | Sunnybrook Health Sciences Centre | Toronto | Ontario |
Canada | UBC Hospital | Vancouver | British Columbia |
Canada | McGill Center for Studies in Aging | Verdun | Quebec |
Colombia | Grupo de Neurociencias Sede de la Universidad de Antioquia | Medellín | |
France | Hopital Neurologique Pierre Wertheimer | Bron cedex | Rhone |
France | Hopital Roger Salengro - CHU Lille | Lille | Nord |
France | Groupe Hospitalier Pitie-Salpetriere | Paris cedex 13 | Paris |
France | CHU de Rouen - Hôpital Charles Nicolle | Rouen | Seine Maritime |
France | CHU de Toulouse - Hôpital Purpan | Toulouse | Haute Garonne |
Germany | LMU-Campus Grosshadern | Muenchen | Bayern |
Germany | Universitaetsklinikum Tubingen | Tübingen | Baden Wuerttemberg |
Ireland | St Vincent's University Hospital | Dublin | |
Italy | IRCCS Centro San Giovanni di Dio Fatebenefratelli | Brescia | |
Italy | Azienda Ospedaliera Universitaria Careggi | Firenze | |
Japan | University of Tokyo Hospital | Bunkyo-Ku | Tokyo-To |
Japan | Niigata University Medical & Dental Hospital | Niigata-shi | Niigata-Ken |
Mexico | Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez | Mexico | Distrito Federal |
Netherlands | Brain Research Center | Amsterdam | |
Puerto Rico | University of Puerto Rico, School of Medicine | San Juan | |
Spain | Hospital Clínic I Provincial de Barcelona | Barcelona | |
United Kingdom | The National Hospital for Neurology and Neurosurgery | London | Greater London |
United States | Emory University | Atlanta | Georgia |
United States | University of Alabama in Birmingham | Birmingham | Alabama |
United States | Kerwin Medical Center | Dallas | Texas |
United States | Indiana University School of Medicine | Indianapolis | Indiana |
United States | University of California San Diego Medical Center | La Jolla | California |
United States | USC Keck School of Medicine | Los Angeles | California |
United States | Yale University School of Medicine | New Haven | Connecticut |
United States | Advocate Lutheran General Hospital | Park Ridge | Illinois |
United States | University of Pittsburgh | Pittsburgh | Pennsylvania |
United States | Butler Hospital | Providence | Rhode Island |
United States | Washington University in St. Louis | Saint Louis | Missouri |
United States | University of Washington | Seattle | Washington |
Lead Sponsor | Collaborator |
---|---|
Washington University School of Medicine | Accelerating Medicines Partnership (AMP), Alzheimer's Association, Avid Radiopharmaceuticals, Eisai Inc., Eli Lilly and Company, Hoffmann-La Roche, Janssen, LP, National Institute on Aging (NIA) |
United States, Argentina, Australia, Brazil, Canada, Colombia, France, Germany, Ireland, Italy, Japan, Mexico, Netherlands, Puerto Rico, Spain, United Kingdom,
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
* Note: There are 11 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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) | Baseline and Weeks 52, 104, 156, and 208 |
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