A Study of Crenezumab Versus Placebo to Evaluate the Efficacy and Safety in Participants With Prodromal to Mild Alzheimer's Disease (AD)
- Registration Number
- NCT03114657
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This randomized, double-blind, placebo-controlled, parallel-group study will evaluate the efficacy and safety of crenezumab versus placebo in participants with prodromal to mild AD. Participants will be randomized 1:1 to receive either intravenous (IV) infusion of crenezumab or placebo every 4 weeks (Q4W) for 100 weeks. The primary efficacy assessment will be performed at 105 weeks. The participants who do not enter open-label extension will enter for a long term follow-up period for up to 52 weeks after the last crenezumab dose (Week 153).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 806
- Weight between 40 and 120 kilograms (Kg) inclusive
- Availability of a person (referred to as the "caregiver") who in the investigator's judgment:
- Has frequent and sufficient contact with the participant to be able to provide accurate information regarding the participant's cognitive and functional abilities, agrees to provide information at clinic visits (which require partner input for scale completion), signs the necessary consent form, and has sufficient cognitive capacity to accurately report upon the participant's behavior and cognitive and functional abilities
- Fluency in the language of the tests used at the study site
- Adequate visual and auditory acuity, in the investigator's judgment, sufficient to perform the neuropsychological testing (eye glasses and hearing aids are permitted)
- Evidence of the AD pathological process, by a positive amyloid assessment either on cerebrospinal fluid (CSF) amyloid beta 1-42 levels as measured on the Elecsys beta-amyloid(1-42) test system or amyloid PET scan by qualitative read by the core/central PET laboratory
- Demonstrated abnormal memory function at screening (up to 4 weeks before screening begins) or screening (FCSRT cueing index =<0.67 AND free recall =<27)
- Screening mini mental state examination (MMSE) score of greater than or equal to (>=) 22 points and Clinical Dementia Rating-Global Score (CDR-GS) of 0.5 or 1.0
- Meets National Institute on Aging/Alzheimer's Association (NIAAA) core clinical criteria for probable AD dementia or prodromal AD (consistent with the NIAAA diagnostic criteria and guidelines for mild cognitive impairment (MCI)
- If receiving symptomatic AD medications, the dosing regimen must have been stable for 3 months prior to screening
- Participant must have completed at least 6 years of formal education after the age of 5 years
- Any evidence of a condition other than AD that may affect cognition such as other dementias, stroke, brain damage, autoimmune disorders (e.g. multiple sclerosis) or infections with neurological sequelae.
- History of major psychiatric illness such as schizophrenia or major depression (if not considered in remission)
- At risk of suicide in the opinion of the investigator
- Any abnormal MRI findings, such as presence of cerebral vascular pathology, cortical stroke, etc or inability to tolerate MRI procedures or contraindication to MRI
- Unstable or clinically significant cardiovascular (e.g., myocardial infarction), kidney or liver disease
- Uncontrolled hypertension
- Screening hemoglobin A1c (HbA1C) >8%
- Poor peripheral venous access
- History of cancer except:
If considered to be cured or If not being actively treated with anti-cancer therapy or radiotherapy
- Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants received intravenous (IV) infusion of Placebo every 4 weeks (Q4W) for 100 weeks. Crenezumab Crenezumab Participants received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W) for 100 weeks.
- Primary Outcome Measures
Name Time Method Change From Baseline to Week 77 in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Scale Score Baseline, Week 77 The CDR-SB rates impairment in 6 categories (memory, orientation, judgement and problem solving, community affairs, home and hobbies and personal care) on a 5-point scale in which no impairment = 0, questionable impairment = 0.5 and mild, moderate and severe impairment = 1, 2 and 3 respectively. The score range is from 0 to 18 with a high score indicating a high disease severity. The difference in mean change from Baseline to Week 77 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline for this primary endpoint. Data after 29 January 2019 are censored for the primary and secondary efficacy analyses to avoid potential biases due to investigators, participants, raters, etc. being potentially influenced by early closure of the study due to lack of efficacy.
- Secondary Outcome Measures
Name Time Method Change From Baseline to Week 77 in Alzheimer's Disease Assessment Scale-Cognition 13 (ADAS-Cog-13) Subscale Score Baseline, Week 77 The ADAS-Cog-13 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Most of these are assessed by tests although some are rated by the clinician on a 5-point scale. The ADAS-Cog-13 is the ADAS-Cog-11 with 2 further items: delayed word recall and total digit cancellation. The score range for ADAS-Cog-13 is from 0 to 85 with high scores representing severe dysfunction. The difference in mean change from Baseline to Week 77 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
Change From Baseline to Week 77 in Alzheimer's Disease Assessment Scale-Cognition 11 (ADAS-Cog-11) Subscale Score Baseline, Week 77 The ADAS-Cog-11 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Most of these are assessed by tests although some are rated by the clinician on a 5-point scale. The score range for ADAS-Cog-11 is from 0 to 70 with high scores representing severe dysfunction. The difference in mean change from Baseline to Week 77 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
Change From Baseline to Week 77 on Severity of Dementia, Assessed Using the CDR-Global Score (CDR-GS) Baseline, Week 77 The CDR-GS represents a semi-structured interview which rates impairment in 6 categories (memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care) on a 5-point scale in which CDR 0 = no dementia and CDR 0.5, 1, 2 or 3 = questionable, mild, moderate or severe dementia respectively. The range in scores for the CDR-GS is from 0 to 3 and a high score on the CDR-GS would indicate a high disease severity. The difference in mean change from Baseline to Week 77 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
Change From Baseline to Week 77 on Severity of Dementia, Assessed Using the Mini Mental State Evaluation (MMSE) Baseline, Week 77 The MMSE is a set of standardized questions used to evaluate possible cognitive impairment and help stage the severity level of this impairment. The questions target 6 areas: orientation, registration, attention, short-term recall, language and constructional praxis/visuospatial abilities. The scores on the MMSE range from 0 to 30, with higher scores indicating better function. The difference in mean change from Baseline to Week 77 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
Change From Baseline to Week 77 on Function as Assessed by (ADCS-ADL) Total Score Baseline, Week 77 The ADCS-ADL (Alzheimer's Disease Cooperative Study-Activities of Daily Living) is the scale most widely used to assess functional outcomes in participants with AD. The ADCS-ADL covers both basic ADL (e.g., eating and toileting) and more complex 'instrumental' ADL or iADL (e.g., using the telephone, managing finances and preparing a meal). The ADCS-ADL consists of 23 questions with a score range of 0 to 78 where a higher score represents better function. The difference in mean change from Baseline to Week 77 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
Change From Baseline to Week 77 on Function as Assessed by (ADCS-iADL) Instrumental Score Baseline, Week 77 The ADCS-iADL (Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living) measures activities such as using the telephone, managing finances and preparing a meal. The ADCS-iADL consists of 16 questions with a score range of 0 to 56 where a higher score represents better function. The difference in mean change from Baseline to Week 77 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
Change From Baseline to Week 77 on Function as Assessed by the Functional Activities Questionnaire (FAQ) Total Score Baseline, Week 77 The Functional Activities Questionnaire (FAQ) is an instrument consisting of 10 items and assesses instrumental, social and cognitive functioning. The score range is from 0 to 30 with higher scores representing higher impairment. The difference in mean change from Baseline to Week 77 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
Change From Baseline to Week 77 on a Measure of Dependence Level Assessed From the ADCS-ADL Score Baseline, Week 77 The ADCS-ADL (Alzheimer's Disease Cooperative Study-Activities of Daily Living) is the scale most widely used to assess functional outcomes in participants with AD. The ADCS-ADL covers both basic ADL (e.g., eating and toileting) and more complex 'instrumental' ADL or iADL (e.g., using the telephone, managing finances and preparing a meal). The ADCS-ADL consists of 23 questions with a score range of 0 to 78 where a higher score represents better function. The difference in mean change from Baseline to Week 77 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
Change From Baseline to Week 53 on Behavior in Neuropsychiatric Inventory Questionnaire (NPI-Q) Total Score Baseline, Week 53 The NPI-Q evaluates 12 neuropsychiatric disturbances common in dementia: delusions, hallucinations, agitation, dysphoria, anxiety, apathy, irritability, euphoria, disinhibition, aberrant motor behavior, night-time behavioral disturbances and appetite/eating abnormalities. The severity of each neuropsychiatric symptom is rated on a 3-point scale (mild, moderate and marked). The total severity score range is from 0 to 36 with higher scores representing higher severity. Difference in mean change from Baseline to Week 53 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures adjusting for disease severity, APOEe4 status, geographic region and the use/non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
Quality of Life-Alzheimer's Disease (QoL-AD) Scale Score Baseline, Week 77 The QoL-AD (Quality of Life - Alzheimer's Disease) scale assesses QoL in participants who have dementia. The QoL-AD consists of 13 items covering aspects of participants' relationships with friends and family, physical condition, mood, concerns about finances and overall assessment of QoL. Items are rated on 4-point Likert-type scales ranging from 1 \[poor\] to 4 \[excellent\]. The score range is from 13 to 52, with higher scores indicating a better QoL. The difference in mean change from Baseline to Week 77 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD) Scale Score Baseline, Week 53 The ZCI-AD is a modified version of the Zarit Burden Interview, which was originally designed to reflect the stresses experienced by caregivers of people with dementia. This modified version includes slight modifications in item and title wording (e.g., removal of "your relative" to refer directly to the patient, removal of "burden" from title) and the use of 11-point numerical rating scales. The ZCI-AD scale consists of a total of 30 items. Total scores will be calculated with a total score range from 0 to 300 (higher scores indicate a higher burden on the caregiver). The difference in mean change from Baseline to Week 53 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Domain Scores for Participants Baseline, Week 77 The EQ-5D is a standardized measure of health status designed to provide a simple generic measure of health for clinical and economic appraisal. It is broadly applicable across a wide range of health conditions and treatment. The EQ-5D assesses five domains to provide a health state index. These are anxiety/depression, pain/discomfort, usual activities, mobility, and self-care. The scores on the EQ-5D ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). The difference in mean change from Baseline to Week 77 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
European Quality of Life-5 Dimensions (EQ-5D) Questionnaire Domain Scores for Caregivers Baseline, Week 77 The EQ-5D is a standardized measure of health status designed to provide a simple generic measure of health for clinical and economic appraisal. It is broadly applicable across a wide range of health conditions and treatment. The EQ-5D assesses five domains to provide a health state index. These are anxiety/depression, pain/discomfort, usual activities, mobility, and self-care. The scores on the EQ-5D ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). The difference in mean change from Baseline to Week 77 between Crenezumab and Placebo treated participants was estimated. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
Percentage of Participants With Adverse Event (AEs) and Serious Adverse Event (SAEs) Baseline up until 16 weeks after the last dose of study drug (up to 117 weeks). An Adverse Event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Percentage of Participants With Anti-Crenezumab Antibodies Baseline up to Week 105 Participants were considered positive or negative for ADA based on their baseline and post-baseline sample results. The number and percentage of participants with confirmed positive ADA levels were determined for Crenezumab and Placebo groups. The prevalence of ADA at baseline was calculated as the proportion of participants with confirmed positive ADA levels at baseline relative to the total number of participants with a sample available at baseline. The incidence of treatment-emergent ADAs was determined as the proportion of participants with confirmed post-baseline positive ADAs relative to the total number of participants that had at least one post-baseline sample available for ADA analysis.
Serum Concentration of Crenezumab Pre-infusion (0 hour), 60-90 minutes post-infusion on Day 1 Week 1 and on Week 25; Weeks 13 (Pre-dose), 37 (Pre-dose), 53 (Pre-dose) and 77 (Pre-dose) (infusion length = as per the Pharmacy Manual) Serum concentration data for Crenezumab will be tabulated and summarized. Descriptive summary statistics will include the arithmetic mean and SD. Since a sparse PK sampling design is being used, population (non-linear mixed-effects) modeling will be used to analyze the dose concentration-time data of crenezumab. Information from other clinical studies may be incorporated to establish the PK model. Please note that Post-dose samples were not collected at Weeks 5, 13, 37, 53 and 77.
Plasma Amyloid Beta (Abeta) 40 Concentrations Week 1 Day 1; Weeks 53 Plasma Abeta 40 concentrations will be measured over time and descriptive summary statistics will include the arithmetic mean and SD. Please note that Pre-dose samples were only collected at Weeks 1 and 53.
Plasma Amyloid Beta (Abeta) 42 Concentrations Week 1 Day 1; Weeks 53 Plasma Abeta 42 concentrations will be measured over time and descriptive summary statistics will include the arithmetic mean and SD. Please note that Pre-dose samples were only collected at Weeks 1 and 53.
Percentage Change From Baseline to Week 105 in Whole Brain Volume as Determined by Magnetic Resonance Imaging (MRI) Baseline, Week 105 Percentage Change in Whole Brain Volume will be measured over time and descriptive summary statistics will include the arithmetic mean, median, range, SD, and coefficient of variation, as appropriate. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
Percentage Change From Baseline to Week 105 in Ventricle Volume as Determined by Magnetic Resonance Imaging (MRI) Baseline, Week 105 Percentage Change in Ventricle Volume will be measured over time and descriptive summary statistics will include the arithmetic mean, median, range, SD, and coefficient of variation, as appropriate. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
Percentage Change From Baseline to Week 105 in Hippocampal Volume as Determined by Magnetic Resonance Imaging (MRI) Baseline, Week 105 Percentage Change in Hippocampal Volume will be measured over time and descriptive summary statistics will include the arithmetic mean, median, range, SD, and coefficient of variation, as appropriate. Mixed model repeated measures (MMRMs) adjusting for disease severity, APOEe4 status, geographic region, and the use or non-use of anti-dementia medications at baseline were used to estimate the mean change from baseline.
Related Research Topics
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Trial Locations
- Locations (211)
Texas Neurology PA
🇺🇸Dallas, Texas, United States
Umberto I Policlinico di Roma-Università di Roma La Sapienza
🇮🇹Roma, Lazio, Italy
Hospital General Universitario de Elche; Servicio de Neurología
🇪🇸Elche, Alicante, Spain
Taipei Medical University - Shuang Ho Hospital - Neurology
🇨🇳New Taipei City, Taiwan
Cleveland Clinic Lou Ruvo; Center for Brain Research
🇺🇸Las Vegas, Nevada, United States
University of Cincinnati; Department of Psychiatry and Behavioral Neuroscience
🇺🇸Cincinnati, Ohio, United States
IRCCS Neuromed; Neurologia I-Centro studio e cura delle demenze e UVA
🇮🇹Pozzilli, Molise, Italy
UCSF - Memory and Aging Center
🇺🇸San Francisco, California, United States
Anderson Clinical Research, Inc.
🇺🇸Redlands, California, United States
MCB Clinical Research Centers
🇺🇸Colorado Springs, Colorado, United States
Health Initiatives Research, PLLC
🇺🇸Fayetteville, Arkansas, United States
Bioclinica Research
🇺🇸Orlando, Florida, United States
Alzheimer's Research and Treatment Center
🇺🇸Lake Worth, Florida, United States
Dayton Center for Neuro Disorders
🇺🇸Dayton, Ohio, United States
Precise Research Centers
🇺🇸Flowood, Mississippi, United States
Advanced Memory Research Institute of NJ
🇺🇸Toms River, New Jersey, United States
Desert Valley Medical Group
🇺🇸Rancho Mirage, California, United States
KI Health Partners, LLC; New England Institute for Clinical Research
🇺🇸Stamford, Connecticut, United States
Renstar Medical Research
🇺🇸Ocala, Florida, United States
Neuropsychiatric Research; Center of Southwest Florida
🇺🇸Fort Myers, Florida, United States
Burke Rehabilitation Hospital
🇺🇸White Plains, New York, United States
Behavioral Health Research
🇺🇸Charlotte, North Carolina, United States
Progressive Medical Research
🇺🇸Port Orange, Florida, United States
The Cognitive and Research Center of New Jersey
🇺🇸Summit, New Jersey, United States
Ohio State University; College of Medicine
🇺🇸Columbus, Ohio, United States
Senior Adults Specialty Research
🇺🇸Austin, Texas, United States
Northeastern Pennsylvania Memory
🇺🇸Plains, Pennsylvania, United States
Abington Neurological Associates
🇺🇸Willow Grove, Pennsylvania, United States
Gadolin Research, LLC
🇺🇸Beaumont, Texas, United States
Neurology Clinic PC
🇺🇸Cordova, Tennessee, United States
Clinical Trials of Texas, Inc
🇺🇸San Antonio, Texas, United States
National Clinical Research Inc.-Richmond
🇺🇸Richmond, Virginia, United States
Universitätsklinikum des Saarlandes Klinik f. Psychiatrie und Psychotherapie
🇩🇪Homburg/Saar, Germany
Pharmakologisches Studienzentrum
🇩🇪Mittweida, Germany
Sheba Medical Center; Psychiatry Department
🇮🇱Ramat Gan, Israel
Instituto de Neurologia de Curitiba
🇧🇷Curitiba, PR, Brazil
AZ Groeninge
🇧🇪Kortrijk, Belgium
Kerwin Research Center, LLC
🇺🇸Dallas, Texas, United States
DAMIC
🇦🇷Cordoba, Argentina
Central Coast Neurosciences Research
🇦🇺Erina, New South Wales, Australia
The Queen Elizabeth Hospital; Neurology
🇦🇺Woodville, South Australia, Australia
Universidad Maimonides
🇦🇷Caba, Argentina
Centro Psiquiatria Sandra Ruschel Ltda
🇧🇷Rio de Janeiro, RJ, Brazil
Hornsby Ku-ring-gai Hospital; Division of Rehabilitation & Aged Care
🇦🇺Hornsby, New South Wales, Australia
OCT Research ULC
🇨🇦Kelowna, British Columbia, Canada
CHU de Limoges Hopital Dupuytren; Service de Medecine Geriatrique
🇫🇷Limoges, France
PANAKEIA - Arzneimittelforschung Leipzig GmbH
🇩🇪Leipzig, Germany
True North Clinical Research-Halifax
🇨🇦Halifax, Nova Scotia, Canada
Tianjin Medical University General Hospital
🇨🇳Tianjin (天津), China
Hopital Roger Salengro; Service de Neurologie
🇫🇷Lille, France
Hopital Pellegrin; Cmrr Aquitaine
🇫🇷Bordeaux, France
Hôpital de Jour du Centre pour Personnes Âgées; Louis Pasteur Neurologie
🇫🇷Colmar, France
Clinique Neuro Rive-Sud
🇨🇦Greenfield Park, Quebec, Canada
Hospital das Clinicas - UFMG
🇧🇷Belo Horizonte, MG, Brazil
CHU Rennes - Hopital Pontchaillou
🇫🇷Rennes, France
Hop Guillaume Et Rene Laennec; Cmrr St Herblain
🇫🇷St Herblain, France
Kawartha Centre - Redefining Healthy Aging
🇨🇦Peterborough, Ontario, Canada
St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
Beijing Union Hospital
🇨🇳Beijing, China
Laane-Tallinna Keskhaigla
🇪🇪Tallinn, Estonia
Fondazione IRCCS Istituto Nazionale Neurologico Besta; UO Neuropatologia
🇮🇹Milano, Lombardia, Italy
Tel Aviv Sourasky Medical Center; Department of Neurology
🇮🇱Tel Aviv, Israel
Hôpital Maison Blanche
🇫🇷Reims, France
Universitätsklinikum Freiburg, Zentrum für Geriatrie und Gerontologie
🇩🇪Freiburg, Germany
Hopital Broca
🇫🇷Paris, France
Klinikum rechts der Isar der TU München; Klinik für Psychiatrie und Psychotherapie
🇩🇪München, Germany
NZOZ Dom Sue Ryder
🇵🇱Bydgoszcz, Poland
Clinic for Mental disorders Dr Laza Lazarevic
🇷🇸Belgrade, Serbia
Neurology clinic, Clinical Center of Serbia
🇷🇸Belgrade, Serbia
Hospital Quiron de Madrid; Servicio de Neurologia
🇪🇸Pozuelo de Alarcon, Madrid, Spain
Rakuwakai Otowarehabilitation Hospital
🇯🇵Kyoto, Japan
Irccs Multimedica Santa Maria; Unita' Di Neurologia
🇮🇹Castellanza, Lombardia, Italy
Hanyang University Seoul Hospital
🇰🇷Seoul, Korea, Republic of
Ijinkai Takeda General Hospital
🇯🇵Kyoto, Japan
NHO Shizuoka Institute of Epilepsy and Neurological Disorders
🇯🇵Shizuoka, Japan
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Kanto Central Hospital
🇯🇵Tokyo, Japan
Tokyo Medical University Hospital
🇯🇵Tokyo, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Fujisawa City Hospital
🇯🇵Kanagawa, Japan
Tokyo Metropolitan Geriatric Hospital
🇯🇵Tokyo, Japan
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Dong-A University Hospital
🇰🇷Busan, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
State autonomous institution of healthcare Inter-regional clinical and diagnostic center
🇷🇺Kazan, Russian Federation
Hospital Santa Caterina, Unitat de Valoració de la memoria i les demencies
🇪🇸Salt, Girona, Spain
Akershus universitetssykehus HF; Nevroklinikken S203
🇳🇴Lørenskog, Norway
National Hospital Organization Sagamihara National Hospital
🇯🇵Kanagawa, Japan
Nebbiolo Center for Clinical Trials
🇷🇺Tomsk, Russian Federation
LLC Baltic Medicine
🇷🇺Saint-Petersburg, Sankt Petersburg, Russian Federation
Private Practice; the Osteoporosis Clinic
🇿🇦Johannesburg, South Africa
Clinica Universitaria de Navarra; Servicio de Neurología
🇪🇸Pamplona, Navarra, Spain
Fundació ACE
🇪🇸BArcelon, Barcelona, Spain
Hospital Perpetuo Socorro, Servicio de Geriatria
🇪🇸Albacete, Spain
Kaohsiung Medical University Hospital; Neurology
🇨🇳Kaohsiung, Taiwan
Hacettepe University Medical Faculty; Neurology
🇹🇷Ankara, Turkey
Ondokuz Mayis Univ. Med. Fac.; Neurology
🇹🇷Samsun, Turkey
Hospital la Magdalena; Servicio de Neurologia
🇪🇸Castellon, Spain
Hospital Ramon y Cajal; Servicio de Neurologia
🇪🇸Madrid, Spain
Hospital Universitario de Burgos. Servicio de Neurología
🇪🇸Burgos, Spain
University Southampton NHS Foundation Trust; Wessex Neurologica Centre
🇬🇧Southampton, United Kingdom
The Fritchie Centre, Charlton Lane Centre, Charlon Lane, Leckhampton; The Fritchie Centre
🇬🇧Cheltenham, United Kingdom
Manchester Royal Infirmary
🇬🇧Manchester, United Kingdom
Surrey and Borders NHS Foundation Trust; Brain Science Research Unit
🇬🇧Chertsey, United Kingdom
John Radcliffe Hospital
🇬🇧Oxford, United Kingdom
Aarhus Universitetshospital, Neurologisk Afdeling F, Demensklinikken
🇩🇰Aarhus N, Denmark
Rigshospitalet, Hukommelsesklinikken
🇩🇰København Ø, Denmark
IRCCS Ospedale San Raffaele; Centro Disturbi della Memoria
🇮🇹Milano, Lombardia, Italy
Ospedale S. Maria Nascente; Fondazione Don Gnocchi; Dip. Neurologia Riabilitativa
🇮🇹Milano, Lombardia, Italy
Skånes Universitetssjukhus Malmö, Minneskliniken
🇸🇪Malmö, Sweden
National Hospital Organization Hiroshima-Nishi Medical Center
🇯🇵Hiroshima, Japan
National Hospital Organization Matsumoto Medical Center
🇯🇵Nagano, Japan
Katayama Medical Clinic
🇯🇵Okayama, Japan
Osaka University Hospital
🇯🇵Osaka, Japan
Shinjuku Research Park Clinic
🇯🇵Tokyo, Japan
National Center of Neurology and Psychiatry
🇯🇵Tokyo, Japan
Tokyo Medical University Hachioji Medical Center
🇯🇵Tokyo, Japan
Asakayama General Hospital
🇯🇵Osaka, Japan
Istanbul University Istanbul School of Medicine; Neurology
🇹🇷Istanbul, Turkey
Charing Cross Hospital; Imperial Memory Unit, Level 10 West
🇬🇧London, United Kingdom
RE:Cognition Health
🇬🇧London, United Kingdom
Queen Elizabeth University Hospital; Clinical Research Facility
🇬🇧Glasgow, United Kingdom
Clínica Dr. Norton Sayeg LTDA - EPP
🇧🇷Sao Paulo, SP, Brazil
Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Neurologia
🇪🇸Santiago de Compostela, LA Coruña, Spain
Hospital Universitario Reina Sofia; Servicio de Neurologia
🇪🇸Cordoba, Spain
CAE Oroitu
🇪🇸BaraKaldo, Vizcaya, Spain
Hospital Universitario Virgen Macarena; Servicio de Neurologia
🇪🇸Sevilla, Spain
University of Nebraska Medical Center; Dept of Neurological Sciences
🇺🇸Omaha, Nebraska, United States
Summit Research Network Inc.
🇺🇸Portland, Oregon, United States
City Clinical Psychiatry Hospital #1
🇷🇺Nizhny Novgorod, Russian Federation
St Nicolas Psychiatric Hospital; Chair of Psychiatry and Narcology of St. Petersburg Medical Academy
🇷🇺St Petersburg, Russian Federation
Institution of RAMS (Mental Health Research Center of RAMS)
🇷🇺Moscow, Russian Federation
Seoul St Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Borame Medical Center
🇰🇷Seoul, Korea, Republic of
Wake Research Associates
🇺🇸Raleigh, North Carolina, United States
JEM Research LLC
🇺🇸Atlantis, Florida, United States
Devonshire Clinical Research Inc.
🇨🇦Woodstock, Ontario, Canada
CHU de Rouen Hopital; Service de Neurologie
🇫🇷Rouen, France
True North Clinical Research Kentville
🇨🇦Kentville, Nova Scotia, Canada
Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Rambam Medical Center
🇮🇱Haifa, Israel
CH Pitie Salpetriere; IM2A
🇫🇷Paris, France
Imaging End Points Clinical Research
🇺🇸Scottsdale, Arizona, United States
Clinical Trials Inc.
🇺🇸Little Rock, Arkansas, United States
Research Center for Clinical Studies, Inc.
🇺🇸Norwalk, Connecticut, United States
Bradenton Research Center
🇺🇸Bradenton, Florida, United States
Lake Charles Clinical Trials, LLC
🇺🇸Lake Charles, Louisiana, United States
Health Partners Institute for Education and Research
🇺🇸Saint Paul, Minnesota, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Hospital Italiano
🇦🇷Buenos Aires, Argentina
Alzheimers Disease & Memory Disorders Center; Department of Neurology Baylor College of Medicine
🇺🇸Houston, Texas, United States
Sentara Medical Group
🇺🇸Norfolk, Virginia, United States
CCBR - Brasilia
🇧🇷Brasilia, DF, Brazil
Hospital das Clinicas - UFRGS
🇧🇷Porto Alegre, RS, Brazil
Providence Care; Mental Health Services
🇨🇦Kingston, Ontario, Canada
ALPHA Recherche Clinique
🇨🇦Quebec, Canada
Hopital des Charpennes
🇫🇷Villeurbanne, France
Klinikum Joh.Wolfg.Goethe-UNI Zentrum d. Psychiatrie Klinik f. Psychiatrie Psychosomatik
🇩🇪Frankfurt, Germany
Ospedale San Giovanni Calibita Fatebenefratell;Neurologia
🇮🇹Roma, Lazio, Italy
IRCCS "Centro S. Giovanni di Dio" Fatebenefratelli -UO Alzheimer
🇮🇹Brescia, Lombardia, Italy
Ospedale Casati Passirana di Rho; Centro Regionale Alzheimer
🇮🇹Passirana, Lombardia, Italy
AO Città della Salute e della Scienza Osp.S.Giov.Battista Molinette; SC Geriatria
🇮🇹Torino, Piemonte, Italy
A.O. Universitaria Pisana; Neurologia
🇮🇹Pisa, Toscana, Italy
Tsukazaki Hospital
🇯🇵Hyogo, Japan
National Center for Geriatrics and Gerontology
🇯🇵Aichi, Japan
Inage Neurology and Memory Clinic
🇯🇵Chiba, Japan
Fukuoka Mirai Hospital
🇯🇵Fukuoka, Japan
Kagawa Prefectural Central Hospital
🇯🇵Kagawa, Japan
Iwate Medical University Hospital
🇯🇵Iwate, Japan
Konkuk University Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Nacional Dos de Mayo; Unidad de Investigacion de Neurologia
🇵🇪Lima, Peru
Hospital Pedro Hispano; Servico de Neurologia
🇵🇹Matosinhos, Portugal
State Healthcare Institution of Sverdlovsk Region Sverdlovsk Regional Clinical Psychiatric Hospita
🇷🇺Ekaterinburg, Sverdlovsk, Russian Federation
Centrum Medyczne Euromedis Sp. z o.o.
🇵🇱Szczecin, Poland
Clinica Internacional; Unidad De Investigacion
🇵🇪Lima, Peru
State Autonomous Healthcare Institution "Republican Clinical Neurological Center
🇷🇺Kazan, Russian Federation
Hospital Mutua De Terrasa; Servicio de Neurologia
🇪🇸Terrassa, Barcelona, Spain
Hospital General De Catalunya; Servicio de Neurologia
🇪🇸Sant Cugat del Valles, Barcelona, Spain
Hospital San Pedro; Servicio de Neurología
🇪🇸Logroño, LA Rioja, Spain
Hospital Universitario Marques de Valdecilla; Servicio de Neurología
🇪🇸Santander, Cantabria, Spain
Policlínica Guipuzkoa; Servicio de Neurología
🇪🇸Donosti-San Sebastián, Guipuzcoa, Spain
Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia
🇪🇸Barcelona, Spain
Sahlgrenska Academy University,Neuroscience and Physiology;Departmt of Psychiatry and Neurochemistry
🇸🇪Mölndal, Sweden
Changhua Christian Hospital; Neurology
🇨🇳Changhua County, Taiwan
Complejo Asistencial Universitario de Salamanca; Servicio de Psiquiatría; CSM La Alamedilla
🇪🇸Salamanca, Spain
National Taiwan University Hospital; Neurology
🇨🇳Taipei, Taiwan
Sussex Partnership NHS Foundation Trust; Cognitive Treatment and Research unit
🇬🇧Crowborough, United Kingdom
NHS Lothian - Western General Hospital; NHS Lothian - Western General Hospital
🇬🇧Edinburgh, United Kingdom
Alzheimers Disease Center; Neurology
🇺🇸Winchester, Massachusetts, United States
Neuro-Therapeutics Inc.
🇺🇸Pasadena, California, United States
Columbus Memory Center
🇺🇸Columbus, Georgia, United States
St Vincent's Hospital Sydney
🇦🇺Darlinghurst, New South Wales, Australia
The Centre for Memory and Aging
🇨🇦Toronto, Ontario, Canada
ECRC Experimental and Clinical Research Center, Charité Campus Berlin Buch, Memory Clinic
🇩🇪Berlin, Germany
Ninewells Hospital
🇬🇧Dundee, United Kingdom
Vancouver Island Health Authority
🇨🇦Victoria, British Columbia, Canada
AZ Sint Jan
🇧🇪Brugge, Belgium
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
Centrum Medyczne NeuroProtect
🇵🇱Warszawa, Poland
NZOZ WCA
🇵🇱Wrocław, Poland
Hospital Geral de Santo Antonio; Servico de Neurologia
🇵🇹Porto, Portugal
HUC; Servico de Neurologia
🇵🇹Coimbra, Portugal
Clinic for neurology, Clinical Center Kragujevac
🇷🇸Kragujevac, Serbia
Chang Gung Memorial Foundation - Linkou - Neurology
🇨🇳Taoyuan, Taiwan
Azienda Ospedaliera Universitaria Policlinico Tor Vergata; Neurologia
🇮🇹Roma, Lazio, Italy
Oslo universitetssykehus HF Ullevål sykehus; Hukommelsesklinikken
🇳🇴Oslo, Norway
Hospital de Braga; Servico de Neurologia
🇵🇹Braga, Portugal
Hospital Virgen del Puerto. Servicio de Neurología
🇪🇸Plasencia, Caceres, Spain
University of California, Davis; Alzheimers Disease Center, Department of Neurology
🇺🇸Sacramento, California, United States
Parkwood Hospital; Geriatric Medicine
🇨🇦London, Ontario, Canada
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States