Alzheimer's Disease Neuroimaging Initiative 2 (ADNI2)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Northern California Institute of Research and Education
Information provided by (Responsible Party):
Alzheimer's Disease Cooperative Study (ADCS)
ClinicalTrials.gov Identifier:
NCT01231971
First received: October 27, 2010
Last updated: January 25, 2014
Last verified: January 2014
  Purpose

The purpose of this study is to build upon the information obtained in the original Alzheimer's Disease Neuroimaging Initiative (ADNI1) and ADNI-GO (Grand Opportunity; a study funded through an NIH grant under the American Recovery and Reinvestment Act), to examine how brain imaging technology can be used with other tests to measure the progression of mild cognitive impairment (MCI) and early Alzheimer's disease (AD). ADNI2 seeks to inform the neuroscience of AD. This information will aid in the early detection of AD, and in measuring the effectiveness of treatments in future clinical trials.


Condition
Mild Cognitive Impairment (MCI)
Alzheimer's Disease

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Alzheimer's Disease Neuroimaging Initiative 2

Resource links provided by NLM:


Further study details as provided by Alzheimer's Disease Cooperative Study (ADCS):

Primary Outcome Measures:
  • Rate of volume change of whole brain, hippocampus and other structural MRI measures [ Time Frame: 4 Years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Rate of Decline as measured by: Cognitive Tests, Activities of Daily Living, and CDR Sum of Boxes [ Time Frame: 4 Years ] [ Designated as safety issue: No ]
  • Rate of conversion will be evaluated among all five groups [ Time Frame: 4 Years ] [ Designated as safety issue: No ]
  • Rates of change on each specified biochemical biomarker [ Time Frame: 4 Years ] [ Designated as safety issue: No ]
  • Rates of change of glucose metabolism (FDG-PET) [ Time Frame: 4 Years ] [ Designated as safety issue: No ]
  • Extent of amyloid deposition as measured by Florbetapir F 18 [ Time Frame: 4 Years ] [ Designated as safety issue: No ]
  • Group differences for each imaging and biomarker measurement [ Time Frame: 4 Years ] [ Designated as safety issue: No ]
  • Correlations among biomarkers and biomarker change [ Time Frame: 4 Years ] [ Designated as safety issue: No ]
  • APOE genotype, low CSF Aβ42, positive amyloid imaging with Florbetapir F 18 [ Time Frame: 4 Years ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

blood, urine, cerebrospinal fluid


Estimated Enrollment: 650
Study Start Date: January 2011
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
Cognitively Normal (CN)
150 newly enrolled participants with no apparent memory problems, and CN participants followed from the ADNI1 study
Early Mild Cognitive Impairment (EMCI)
100 newly enrolled early amnestic MCI participants, and approximately 200 EMCI participants will be followed from the ADNI-GO study
Late Mild Cognitive Impairment (LMCI)
150 newly enrolled late MCI participants, and LMCI participants followed from the ADNI1 study
Alzheimer's Disease (AD)
150 newly enrolled mild AD participants
Significant Memory Concern (SMC)
100 newly enrolled participants with Significant Memory Concern (SMC)

Detailed Description:

The Alzheimer's Disease Neuroimaging Initiative (ADNI) began in October 2004 as a landmark study with a public-private partnership that gathered and analyzed thousands of brain scans, genetic profiles and biomarkers in blood and cerebrospinal fluid (CSF). Although the original goal was to define biomarkers for use in clinical trials to determine the best way to measure treatment effects of Alzheimer's disease (AD), the goal has been expanded to using biomarkers to identify AD at a pre-dementia stage. ADNI1 involves scientists at 59 research centers, 54 in the U.S. and five in Canada. Originally 800 participants were enrolled. This group was comprised of 200 participants with AD, 400 with mild cognitive impairment (MCI) and 200 with normal cognition. In ADNI-GO, an estimated 200 participants with early amnestic MCI (EMCI) were enrolled to understand and characterize the mildest symptomatic phase of AD. An additional 650 participants will be enrolled under ADNI2.

Some of the leading-edge technologies under study are brain-imaging techniques, such as positron emission tomography (PET), including FDG-PET (which measures glucose metabolism in the brain); PET using a radioactive compound (Florbetapir F 18) that measures brain beta-amyloid; and structural MRI. Brain scans are showing scientists how the brain's structure and function change as AD starts and progresses. Biomarkers in cerebrospinal fluid are revealing other changes that could identify which patients with MCI will develop Alzheimer's. Scientists are looking at levels of beta-amyloid and tau in cerebrospinal fluid. (Abnormal amounts of the amyloid and tau proteins in the brain are hallmarks of Alzheimer's disease.)

ADNI2 extends the work of ADNI1 and ADNI GO to understand the progression of AD. The overall goal is to determine the relationships among the clinical, cognitive, imaging, genetic and biochemical biomarker characteristics of the entire spectrum of AD, as the pathology evolves from normal aging through very mild symptoms, to MCI, to dementia.

The overall impact of this study will be increased knowledge concerning the sequence and timing of events leading to MCI and AD, development of better clinical and imaging/fluid biomarker methods for early detection and for monitoring the progression of these conditions, and facilitation of clinical trials to slow disease progression, ultimately contributing to the prevention of AD.

  Eligibility

Ages Eligible for Study:   55 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

Community Sample

Criteria

Inclusion Criteria:

Participants will be classified as either normal controls, SMC, EMCI, LMCI or AD participants. General Inclusion Criteria will apply to all groups, with specific criteria for each group as described below:

General (applies to each category):

  • Geriatric Depression Scale less than 6.
  • Age between *55-90 (inclusive). *For normal controls and SMC participants, age must be between 65-90.
  • Study partner is available who has frequent contact with the participant (e.g. an average of 10 hours per week or more), and can accompany the participant to all clinic visits for the duration of the protocol.
  • Visual and auditory acuity adequate for neuropsychological testing.
  • Good general health with no diseases expected to interfere with the study.
  • Participant is not pregnant, lactating, or of childbearing potential (i.e. women must be two years post-menopausal or surgically sterile).
  • Willing and able to participate in a longitudinal imaging study.
  • Hachinski less than or equal to 4.
  • Completed six grades of education or has a good work history (sufficient to exclude mental retardation).
  • Must speak English or Spanish fluently.
  • Willing to undergo repeated MRIs (3Tesla) and at least two PET scans (one FDG and one Amyloid imaging) and no medical contraindications to MRI.
  • Agrees to collection of blood for Genome Wide Association Studies (GWAS), APOE testing and DNA and RNA banking.
  • Agrees to collection of blood for biomarker testing.
  • Agrees to at least one lumbar puncture for the collection of CSF.

Specific Inclusion Criteria for normal controls:

  • Participant must be free of memory complaints, verified by a study partner.
  • Normal memory function score on Wechsler Memory Scale (adjusted for education)
  • Mini-Mental State Exam (MMSE) score between 24 and 30 (inclusive)
  • Clinical Dementia Rating (CDR) = 0; Memory Box score must be 0
  • Cognitively normal, based on an absence of significant impairment in cognitive functions or activities of daily living
  • Stability of Permitted Medications for 4 weeks. In particular, participants may take:

    • Antidepressants lacking significant anticholinergic side effects
    • Estrogen replacement therapy is permissible
    • Gingko biloba is permissible, but discouraged
    • Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening

Specific Inclusion Criteria for SMC participants:

  • Subjects that are "self-referrals" that have a significant subjective memory concern
  • Significant memory concern confirmed by a Cognitive Change Index score of more than or equal to 16
  • Normal memory function score on Wechsler Memory Scale (adjusted for education)
  • Mini-Mental State Exam (MMSE) score between 24 and 30 (inclusive)
  • Clinical Dementia Rating (CDR) = 0; Memory Box score must be 0
  • Cognitively normal, based on the absence of significant memory impairment in cognitive function or activities of daily living
  • Stability of Permitted Medications for 4 weeks. In particular, subjects may take:

    • Antidepressants lacking significant anticholinergic side effects
    • Estrogen replacement therapy is permissible
    • Gingko biloba is permissible, but discouraged
    • Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening

Specific Inclusion Criteria for EMCI and LMCI participants:

  • Participant must have a subjective memory concern as reported by participant, study partner, or clinician
  • Abnormal memory function score on Wechsler Memory Scale (adjusted for education)
  • Mini-Mental State Exam (MMSE) score between 24 and 30 (inclusive)
  • Clinical Dementia Rating (CDR) = 0.5; Memory Box score must be at least 0.5
  • General cognition and functional performance sufficiently preserved such that a diagnosis of AD cannot be made by the site physician at the time of the screening visit
  • Stability of Permitted Medications for 4 weeks. In particular, participants may take:

    • Antidepressants lacking significant anticholinergic side effects
    • Estrogen replacement therapy
    • Gingko biloba is permissible, but discouraged
    • Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening
    • Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to screening

Specific Inclusion Criteria for AD participants:

  • Participant must have a subjective memory concern as reported by participant, study partner, or clinician
  • Abnormal memory function score on Wechsler Memory Scale (adjusted for education)
  • Mini-Mental State Exam (MMSE) score between 20 and 26 (inclusive)
  • Clinical Dementia Rating (CDR) = 0.5 or 1.0
  • National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable AD
  • Stability of Permitted Medications for 4 weeks. In particular, participants may take:

    • Antidepressants lacking significant anticholinergic side effects
    • Estrogen replacement therapy
    • Gingko biloba is permissible, but discouraged
    • Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening
    • Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to screening

Specific Inclusion Criteria for follow-up participants from ADNI1 and ADNI GO:

  • Must have been enrolled and followed in ADNI1 for at least one year or enrolled in ADNI-GO with original diagnosis of Cognitively Normal (CN), Mild Cognitive Impairment (MCI), or Early Mild Cognitive Impairment (EMCI) regardless of whether a diagnostic conversion has occurred since initial enrollment in ADNI.
  • Willing and able to continue to participate in an ongoing longitudinal study. A reduced battery of tests is allowable if the participant is not able/willing to complete the full battery.
  • Study partner is available who has frequent contact with the participant (e.g. an average of 10 hours per week or more), and can accompany the participant to all clinic visits for the duration of the protocol.

Exclusion Criteria:

General (applies to each category):

  • Screening/baseline MRI scan with evidence of infection, infarction, or other focal lesions; Participants with multiple lacunes or lacunes in a critical memory structure are excluded
  • Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body
  • Major depression, bipolar disorder as described in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) within the past 1 year
  • Currently treated with medication for obsessive-compulsive disorder or attention deficit disorder
  • History of schizophrenia
  • History of alcohol or substance abuse or dependence within the past 2 years
  • Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol
  • Clinically significant abnormalities in B12, or TFTs that might interfere with the study
  • Residence in skilled nursing facility
  • Current use of specific psychoactive medications (e.g.,certain antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.); Current use of warfarin or dabigatran (exclusionary for lumbar puncture).
  • Use of investigational agents one month prior to entry and for the duration of the trial
  • Participation in clinical studies involving neuropsychological measures being collected more than one time per year
  • Exclusion for FDG PET scan and amyloid imaging with Florbetapir F 18: Current or recent participation in any procedures involving radioactive agents such that the total radiation dose exposure to the participant in any given year would exceed the limits of annual and total dose commitment set forth in the US Code of Federal Regulations (CFR) Title 21 Section 361.1.
  • Exceptions to these guidelines may be considered on a case-by-case basis at the discretion of the protocol director

Specific Exclusion Criteria for normal controls and SMC participants:

  • Any significant neurologic disease, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities

Specific Exclusion Criteria for EMCI and LMCI participants:

  • Any significant neurologic disease other than suspected incipient Alzheimer's disease, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities.

Specific Exclusion Criteria for AD participants:

  • Any significant neurologic disease other than Alzheimer's disease, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities.

Specific Exclusion Criteria for follow-up participants from ADNI1 and ADNI GO:

  • Participants will not be able to participate in FDG PET scan and amyloid imaging with Florbetapir F 18 if the following is true: Current or recent participation in any procedures involving radioactive agents such that the total radiation dose exposure to the participant in any given year would exceed the limits of annual and total dose commitment set forth in the US Code of Federal Regulations (CFR) Title 21 Section 361.1.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01231971

  Show 59 Study Locations
Sponsors and Collaborators
Alzheimer's Disease Cooperative Study (ADCS)
Northern California Institute of Research and Education
Investigators
Principal Investigator: Ronald Petersen, MD, PhD Mayo Clinic
Principal Investigator: Michael W. Weiner, MD University of California, San Francisco
Principal Investigator: Paul S. Aisen, MD University of California, San Diego
  More Information

Additional Information:
Publications:
Responsible Party: Alzheimer's Disease Cooperative Study (ADCS)
ClinicalTrials.gov Identifier: NCT01231971     History of Changes
Other Study ID Numbers: ADC-039-ADNI2
Study First Received: October 27, 2010
Last Updated: January 25, 2014
Health Authority: United States: Federal Government

Keywords provided by Alzheimer's Disease Cooperative Study (ADCS):
amyloid
plaques
neuroimaging
biomarkers
cognition disorder
early detection
Amnestic MCI
pre-dementia
dementia
Alzheimer's disease

Additional relevant MeSH terms:
Alzheimer Disease
Cognition Disorders
Mild Cognitive Impairment
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on August 27, 2014