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Cognitive Health in Ageing Register: Investigational, Observational and Trial Studies in Dementia Research: Prospective Readiness Cohort Study (CHARIOT:PRO)

This study is currently recruiting participants.
Verified September 2017 by Janssen Research & Development, LLC
Sponsor:
ClinicalTrials.gov Identifier:
NCT02114372
First Posted: April 15, 2014
Last Update Posted: September 25, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Janssen Research & Development, LLC
  Purpose

The purpose of this study is (i) Main Study: To describe the baseline characteristics (including demographics, cognitive status, and other measures) and the cognitive and functional changes of persons at risk for developing Alzheimer's disease (AD).

(ii) SubStudy: To investigate the longitudinal change of the components of the Preclinical Alzheimer Cognitive Composite (PACC) and the components of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in asymptomatic at risk for AD (ARAD) individuals compared with individuals not classified as ARAD.

(iii) Neurovision Ancillary Study: To explore correlation between retinal amyloid beta plaques identified by fluorescence with amyloid positron emission tomography (PET) Standardized Uptake Value Ratio (SUVR) and cerebrospinal fluid (CSF) amyloid beta 42 testing in participants at risk for Alzheimer's dementia.


Condition
Alzheimer's Disease Plaque, Amyloid

Study Type: Observational
Study Design: Observational Model: Ecologic or Community
Time Perspective: Prospective
Official Title: Cognitive Health in Ageing Register: Investigational, Observational and Trial Studies in Dementia Research (CHARIOT): Prospective Readiness Cohort Study (PRO)

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Main Study: Change From Baseline Cognition [ Time Frame: Up to 4 years ]
    Cognition will be evaluated at baseline and longitudinally with the Mini-Mental State Examination (MMSE), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Neuropsychological Assessment Battery (NAB)-Executive Function module, NAB-Memory module, CogState Brief Battery (CBB), Clinical Drug Research Assessment System (CDR-AS), and Delis Kaplan Executive Function System (DKEFS), as well as the Clinical Dementia Rating Scale.

  • SubStudy: Change From Baseline on Preclinical Alzheimer Cognitive Composite (PACC) Component Score [ Time Frame: Up to 3.5 years ]
    The PACC is a retrospectively validated measure that is weighted towards episodic memory, and also includes a timed executive function test and a global cognitive screening test. The PACC includes: 1. Total Recall score from the Free and Cued Selective Reminding Test [FCSRT] (0-48 words); 2. Delayed Paragraph Recall total score on single administration of the Logical Memory story from the Wechsler Memory Scale [WMS]-Revised (0-25 story units); 3. Digit Symbol Substitution Test score from the Wechsler Adult Intelligence Scale [WAIS]-Revised (0-135 symbols), and 4. MMSE score (0-30 points). The component scores are transformed using an established normalization method into z-scores. Each of the 4 component change scores is divided by the baseline sample standard deviation of that component. Z-score implies how many standard deviations higher or lower the score is compared with the baseline score.

  • SubStudy: Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status-Preclinical Alzheimer Cognitive Composite (RBANS-PACC) Component Score [ Time Frame: Up to 3.5 years ]
    This brief test is for cognitive assessment, detection, and characterization of dementia in the elderly as well as neuropsychological screening for younger patients. The RBANS-PACC includes: 1. RBANS List Learning; 2. RBAN Delayed Story Recall; 3. RBANS Coding; 4. MMSE score; and may also include a fifth component, the RBANS Semantic Fluency. The component scores are transformed using an established normalization method into z-scores. Each of the 4 component change scores is divided by the baseline sample standard deviation of that component. Z-score implies how many standard deviations higher or lower the score is compared with the baseline score.

  • Ancillary Study: Correlation Between the Change in Beta-amyloid Protein (A beta) Plaque Identified by Fluorescence in the Retina With Amyloid PET SUVR and CSF Amyloid Beta 42 [ Time Frame: Up to 6 weeks ]
    A noninvasive optical imaging technique used to detect retinal amyloid plaques following systemic administration of curcumin (a natural plaque-labeling fluorochrome) will be used to investigate the correlation between retinal amyloid plaques and amyloid pathology determined by amyloid PET SUVR or CSF amyloid beta 42.


Secondary Outcome Measures:
  • SubStudy: Change From Baseline on the RBANS-PACC Composite Score [ Time Frame: Up to 3.5 years ]
    This brief test is for cognitive assessment, detection and characterization of dementia in the elderly as well as neuropsychological screening for younger participants. RBANSPACC composite score will be calculated similar to PACC, by replacing 1 or more PACC components as: FCSRT replaced by RBANS List Learning; Delayed Paragraph Recall replaced by RBANS Delayed Story Recall; WAIS-IV Coding replaced by RBANS Coding; MMSE. It may also include a fifth component, RBANS Semantic Fluency. Composite score is determined from its components using an established normalization method. Each of the component change scores is divided by the baseline sample standard deviation of that component, to form standardized z-scores. Z-score implies how many standard deviations higher or lower the score is compared with baseline score. Composite score is a sum of z-scores for component scores. A change of 1 baseline standard deviation on each component would correspond to a 4-point change on the composite.

  • SubStudy: Change From Baseline on the PACC Composite Score [ Time Frame: Up to 3.5 years ]
    The PACC is a retrospectively validated measure that is weighted towards episodic memory, a timed executive function test and a global cognitive screening test. The PACC includes: 1. Total Recall score from FCSRT (0-48 words); 2. Delayed Paragraph Recall total score on single administration of the Logical Memory story from the WMS-Revised (0-25 story units); 3. Digit Symbol Substitution Test score from the WAIS-Revised (0-135 symbols), and 4. MMSE score (0-30 points). The composite score is determined from its components using an established normalization method. Each of the 4 component change scores is divided by the baseline sample standard deviation of that component, to form standardized z-scores. Z-score implies how many standard deviations higher or lower the score is compared with baseline score. The composite score is a sum of z-scores for component scores. Thus, a change of 1 baseline standard deviation on each component would correspond to a 4-point change on the composite.


Biospecimen Retention:   Samples With DNA
Blood, saliva, and urine specimens will be collected.

Estimated Enrollment: 700
Actual Study Start Date: February 5, 2014
Estimated Study Completion Date: March 30, 2022
Estimated Primary Completion Date: August 20, 2020 (Final data collection date for primary outcome measure)
Groups/Cohorts
CogState Brief Battery
Enrolled participants will be randomized in a balanced manner to CogState brief battery in both the Main Study and the SubStudy. CogState consists of four tasks that respectively measure the functions of attention, processing speed, visual learning, and working memory. The CogState Brief Battery is an approximately 15 minute computerized battery with demonstrated reliability, validity, and short term stability, that was developed expressly for maximal sensitivity to detect change. CogState can be administered via the internet or on a stand-alone computer and is available in over 50 languages.
Clinical Drug Research Assessment System (CDR-AS)
Enrolled participants will be randomized in a balanced manner to CDR-AS in both the Main Study and the SubStudy. CDR-AS is fully automated System that targets the core aspects of cognitive function crucial for everyday behavior which are vulnerable to numerous insults including aging, fatigue, disease, pathology, trauma, diet, and pharmaceuticals. CDR-AS is an approximately 20-minute computerized battery designed to reliably measure changes in cognitive function in clinical trial situations.
Delis Kaplan Executive Function System (DKEFS)
Enrolled participants will be randomized in a balanced manner to DKEFS in the Main Study and at one site of the SubStudy. The DKEFS is a paper and pencil measure of verbal and nonverbal executive functions and has been normed and validated for children and adults from 8-89 years of age. The measure consists of nine subtests. For the purposes of this study, the Trail Making Test (TMT) and Verbal Fluency subtests will be used.
COGNITO
Enrolled participants will be randomized in a balanced manner to COGNITO at the other site of the SubStudy. COGNITO is an approximately 45 to 60 minute computerized neuropsychometric examination based on well-known cognitive tests designed for both cognition research and clinical assessment. COGNITO assesses reaction time, primary and working memory, visuospatial and verbal secondary memory, implicit learning, language skills, functional and semantic categorization of visual data, focused and divided attention, and crystallized intelligence. Responses are made via a tactile screen which permits the recording of response latency (deducting reaction time provides an estimation of information processing time).
Retinal Imaging (Ancillary Study)
Participants enrolled in the Ancillary Study will be tested using a retinal imaging system, a scanning ophthalmoscope which uses infrared and blue light to obtain confocal images of the retina to quantify retinal amyloid beta plaques.

Detailed Description:
This is a prospective, non-interventional study consisting of a Main Study, a SubStudy, and an Ancillary 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. The Main Study will be conducted only at one site and the SubStudy and the Ancillary Study will be conducted at two sites. Participants in both the Main Study and the SubStudy 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. 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. The Ancillary Study will explore how measures of retinal amyloid plaques relate to cerebellar amyloid SUVR taken from PET imaging or with amyloid beta 42 levels measured in CSF. Data collection to assess outcome measures associated with disease progression will occur at baseline and every 6 months thereafter at the clinic during the follow-up period of 48 months (Main Study). SubStudy participants will be followed every 3 months throughout the SubStudy and will alternate between completing the alternative forms of the PACC and RBANS for a period of up to 3.5 years. Ancillary Study participants will be followed on Day 1, Days 4-15 and a follow-up call (greater than [30] and less than [<] 35 days after Visit 2). 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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   60 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Main Study includes participants without dementia who are considered at high, medium, and low risk for developing mild cognitive impairment (MCI) due to Alzheimer's disease (AD). 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. Participants enrolled in the SubStudy are eligible for the Ancillary Study. In addition, participants who has completed CHARIOT:PRO SubStudy amyloid screening within 12 months prior to the first Ancillary Study visit and participants who have not met enrollment criteria for the SubStudy based on amyloid status will be enrolled in the Ancillary Study.
Criteria

Inclusion criteria:

  1. Main Study:

    • Enrolled in the CHARIOT Register
    • Willing and able to give written informed consent
    • Meets the definition for inclusion in the low risk, medium risk, or high risk cohorts according to criteria specified in the protocol. Participants for whom an age- and education-adjusted baseline RBANS domain index score is more than 1.5 standard deviation (SD) below normal will be adjudicated for inclusion
  2. SubStudy:

    • Completed RBANS and PACC neurocognitive testing at least once during the SubStudy screening visits
    • Have a global CDR score of 0 at screening
    • Be able to read and write and must have adequate hearing and visual acuity to complete the required psychometric tests
  3. Ancillary Study:

    • Has completed SubStudy amyloid screening using either positron emission tomography (PET) scanning or CSF A beta 42 measurement within 12 months prior to the first Ancillary Study visit and is either enrolled in the SubStudy OR is one of the additional 200 individuals who have not met enrollment criteria for the SubStudy based on amyloid status

Exclusion Criteria:

  1. Main Study:

    • Concurrent participation in a clinical trial
    • Diagnosis of dementia
    • Past or current use of memantine or cholinesterase inhibitors
    • Diagnosis of other neurologic disease or conditions known to cause or be associated with dementia, such as Parkinson's disease
    • History of traumatic brain injury with residual neurological deficit or stroke
  2. SubStudy:

    • Met clinical criteria for AD dementia or has any degenerative brain disorder that is associated with dementia
    • Any known history of familial autosomal dominant Alzheimer's disease or other familial dementing diseases
  3. Ancillary Study:

    • Has advanced retinal disease, advanced cataracts, or other advanced ocular conditions that, in the opinion of the investigator, are likely to affect obtaining clear images of the retina
    • Has had prior ocular surgery within 2 months of planned retinal imaging, or is still taking post-operative ocular medications at first day of retinal imaging
    • Has had major surgery within 4 weeks of Ancillary Study inclusion or has planned surgical procedure during the study period
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02114372


Contacts
Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions: JNJ.CT@sylogent.com

Locations
United Kingdom
Royal Infirmary of Edinburgh Recruiting
Edinburgh, United Kingdom, EH16 4SA
Imperial College of London Recruiting
London, United Kingdom, W6 8RP
Active, not recruiting
London, United Kingdom
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

Additional Information:
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02114372     History of Changes
Other Study ID Numbers: CR104383
REGISTRYALZ0001 ( Other Identifier: Janssen Research & Development, LLC )
RRA-11823 ( Other Identifier: Janssen Research & Development, LLC )
First Submitted: April 11, 2014
First Posted: April 15, 2014
Last Update Posted: September 25, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Janssen Research & Development, LLC:
Alzheimer's disease
Asymptomatic at risk for Alzheimer's disease
Retinal diagnosis for Alzheimer's disease

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Plaque, Amyloid
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Pathological Conditions, Anatomical