Clinical trial NCT02114372: Cognitive Health in Ageing Register: Investigational, Observational and Trial Studies in Dementia Research: Prospective Readiness Cohort Study
Official title: Cognitive Health in Ageing Register: Investigational, Observational and Trial Studies in Dementia Research (CHARIOT): Prospective Readiness Cohort Study (PRO)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Alzheimer's Disease
Plaque, Amyloid
Keywords: Alzheimer's disease
Asymptomatic at risk for Alzheimer's disease
Retinal diagnosis for Alzheimer's disease
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2014-04-15
Enrollment: 1136
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: ECOLOGIC_OR_COMMUNITY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: SubStudy includes participants who have completed Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Preclinical Alzheimer Cognitive Composite (PACC) neurocognitive testing at least once during the SubStudy screening visits and have a baseline global Clinical Dementia Rating scale (CDR) score of 0.

Brief summary: The purpose of this study is to prospectively investigate the longitudinal change of the components of the Preclinical Alzheimer Cognitive Composite (PACC) and the components (index scores) of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in asymptomatic at risk for Alzheimer's disease (ARAD) individuals.

Detailed description: This is a prospective, non-interventional study that will enroll participants without dementia who are considered at high, medium, and low risk for developing AD from a community based register (referred to as the CHARIOT registry) in the United Kingdom. Participants will undergo a series of neuropsychological evaluations to characterize the patterns of cognitive change and their inter-relationship in the earliest stages of cognitive impairment. In addition, how such changes relate to the clinical presentation of cognitive impairment of the Alzheimer's type may be evaluated over time. The SubStudy will investigate the longitudinal change of components of the PACC and RBANS in ARAD individuals who have demonstrable amyloid in the brain by either PET or CSF compared with individuals not classified as ARAD. SubStudy participants will be followed every 6 months throughout the SubStudy and will alternate between completing the alternative forms of the PACC and RBANS for a period of up to 4.5 years (54 months). Blood, urine, and saliva samples will be collected from participants during the study for biomarker analyses to assess risk factors for dementia, Alzheimer's disease or confounding factors of dementia risk. Adverse events experienced by the participants during their participation in the study will be monitored.

Eligibility criteria: Inclusion Criteria:

* Completed Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Preclinical Alzheimer Cognitive Composite (PACC) neurocognitive testing at least once during the SubStudy screening visits
* Have a global Clinical Dementia Rating (CDR) score of 0 at screening
* Be fluent in and able to read and write in English; be willing and able to give written informed consent; and have adequate hearing and visual acuity to complete the required psychometric tests
* Have evidence of amyloid pathology by means of low cerebrospinal fluid (CSF) beta amyloid protein (ABeta42) concentrations at screenings (for amyloid positive cohort only) or have no evidence of amyloid pathology by this criterion (for amyloid negative cohort only) and are selected for inclusion in Cognitive Health in Ageing Register: Investigational, Observational, and Trial studies in dementia research: Prospective Readiness cohort study (CHARIOT-PRO) as per the interactive web response decision algorithm
* Be otherwise in satisfactory health and medically stable on the basis of medical history, vital signs, and physical exam. Any abnormalities must not be the cause or be associated with cognitive impairment

Exclusion Criteria:

* Meets clinical criteria for Alzheimer's disease (AD) dementia, Mild Cognitive Impairment (MCI) diagnosis, or has any degenerative brain disorder that is associated with dementia, such as Parkinson's disease
* Participants whose age- and education-adjusted cognitive performance is more than 1.5 standard deviation (SD) below normal on any of the RBANS Index scores at the first RBANS administration
* Any known history of familial autosomal dominant AD or other familial dementing diseases
* History of or current thyroid disease or thyroid dysfunction, which is currently uncontrolled or untreated, or clinically significant abnormal thyroid function tests. Participants treated for thyroid disease may be enrolled following review of their records of thyroid function, laboratory tests at screening, diagnosis and treatment history by the Investigator or designee
* Any contraindications for magnetic resonance imaging (MRI) (example, pacemaker, metal prostheses, implants, claustrophobia, pacemakers etc) unless MRI compatible

Primary outcomes:
measure: Main Study: Change From Baseline Cognition
timeFrame: Up to 4 years
measure: SubStudy: Change From Baseline on Preclinical Alzheimer Cognitive Composite (PACC) Component Score
timeFrame: Baseline and Month 42 (Year 3.5)
measure: SubStudy: Change From Baseline in RBANS Index Scores
timeFrame: Baseline and Month 42 (Year 3.5)
Secondary outcomes:
measure: SubStudy: Change From Baseline on the RBANS Total Scale
timeFrame: Baseline and Month 42 (Year 3.5)
measure: SubStudy: Change From Baseline on the PACC Composite Score
timeFrame: Baseline and Month 42 (Year 3.5)
Other outcomes:
Locations:
city: Edinburgh
country: United Kingdom
city: London
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Udeh-Momoh CT, Watermeyer T, Price G, de Jager Loots CA, Reglinska-Matveyev N, Ropacki M, Ketter N, Fogle M, Raghavan N, Arrighi M, Brashear R, Di J, Baker S, Giannakopoulou P, Robb C, Bassil D, Cohn M, McLellan-Young H, Crispin J, Lakey K, Lisa C, Chowdary Seemulamoodi Y, Kafetsouli D, Perera D, Car J, Majeed A, Ward H, Ritchie K, Perneczky R, Kivipelto M, Scott D, Bracoud L, Saad Z, Novak G, Ritchie CW, Middleton L. Protocol of the Cognitive Health in Ageing Register: Investigational, Observational and Trial Studies in Dementia Research (CHARIOT): Prospective Readiness cOhort (PRO) SubStudy. BMJ Open. 2021 Jun 24;11(6):e043114. doi: 10.1136/bmjopen-2020-043114.