Alzheimer's Disease Neuroimaging Initiative Grand Opportunity (ADNI-GO)

This study has been completed.
Sponsor:
Collaborators:
Northern California Institute of Research and Education
Information provided by (Responsible Party):
Alzheimer's Disease Cooperative Study (ADCS)
ClinicalTrials.gov Identifier:
NCT01078636
First received: March 1, 2010
Last updated: May 15, 2013
Last verified: May 2013
  Purpose

The purpose of this study is to build upon the information obtained in the original Alzheimer's Disease Neuroimaging Initiative (ADNI1), 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). ADNI-GO seeks to define and characterize the mildest symptomatic phase of AD, referred to in this study as early amnestic MCI (EMCI). 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
Alzheimer's Disease

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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Rate of Decline as measured by: Cognitive tests, Activities of Daily Living, and CDR Sum of Boxes [ Time Frame: at screening, baseline, 6 (EMCI only) and 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Rate of conversion will be evaluated among all four groups [ Time Frame: at screening , baseline, 6 (EMCI only) and 12 months ] [ Designated as safety issue: No ]
  • Rate of volume change of whole brain, hippocampus, and other structural MRI measures [ Time Frame: at screening and 3, 6, and 12 months (EMCI); at baseline and 12 months (follow-up patients) ] [ Designated as safety issue: No ]
  • Rates of change on each specified biochemical biomarker [ Time Frame: at baseline, 6 (EMCI only) and 12 months ] [ Designated as safety issue: No ]
  • Rates of change of glucose metabolism (FDG-PET) [ Time Frame: at baseline ] [ Designated as safety issue: No ]
  • Extent of amyloid deposition as measured by 18F-AV-45 [ Time Frame: at baseline ] [ Designated as safety issue: No ]
  • Group differences for each imaging and biomarker measurement [ Time Frame: at screening, baseline, 6 (EMCI only) and 12 months ] [ Designated as safety issue: No ]
  • Correlations among biomarkers and biomarker change [ Time Frame: at screening, baseline, 6 (EMCI only) and 12 months ] [ Designated as safety issue: No ]
  • Subgroups analyses: APOE genotype, low CSF Aβ42, positive amyloid imaging with 18F-AV-45 [ Time Frame: at baseline ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

blood, urine, cerebrospinal fluid


Enrollment: 342
Study Start Date: April 2010
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
EMCI (only cohort recruiting in this study)
Newly recruited early amnestic Mild Cognitive Impairment patients; estimated enrollment 200
LMCI (not recruiting in this study)
Late Mild Cognitive Impairment patients; approximately 400 LMCI participants anticipated to follow from the original ADNI study
CN (not recruiting in this study)
Cognitively Normal patients; approximately 200 CN participants anticipated to follow from the original ADNI study

Detailed Description:

This project continues the work from ADNI1, the goal of which is to test whether serial magnetic resonance imaging (MRI), positron emission tomography (PET), other biological markers, and clinical and neuropsychological assessments can be combined to measure the progression of mild cognitive impairment (MCI) and early Alzheimer's disease (AD). The goal of the study is to determine relationships among the clinical, cognitive, imaging, genetic, and biochemical biomarker characteristics of the stage of the AD spectrum that precedes MCI, the mildest symptomatic phase of AD, referred to here as EMCI. The ADNI-GO model posits that AD begins with amyloid β (Aβ) deposition in the cortex, which leads to synaptic dysfunction, neurodegeneration, and cognitive/ functional decline.

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 (F-AV-45) 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.)

All participants from ADNI1 who are in the normal and MCI stages will continue to be followed in ADNI-GO. The next step is to scan and analyze the brains of people with EMCI; 200 EMCI participants will be enrolled to narrow the gap between cognitively normal (CN) and "late MCI (LMCI)" participants currently enrolled in ADNI.

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 of treatments 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

EMCI Inclusion Criteria:

  • Between 55 and 90 years of age
  • Study partner to accompany patient to all clinic visits for the duration of the protocol
  • Memory complaint by patient and/or study partner
  • Abnormal memory function score on Wechsler Memory Scale (adjusted for education)
  • Mini-Mental State Exam score between 24 and 30 (inclusive)
  • Clinical Dementia Rating = 0.5; Memory Box score at least 0.5
  • General cognition and functional performance sufficiently preserved such that a diagnosis of Alzheimer's disease cannot be made by the site physician at the time of the screening visit
  • Stability of the following permitted medications for 4 weeks (unless stated otherwise):

    • 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 if stable for 12 weeks prior to screening
  • Geriatric Depression Scale less than 6
  • Visual and auditory acuity adequate for neuropsychological testing
  • Good general health with no diseases expected to interfere with the study
  • Not pregnant, lactating, or of childbearing potential (i.e. women must be two years post-menopausal or surgically sterile)
  • Hachinski less than or equal to 4
  • Six grade education or has a good work history (sufficient to exclude mental retardation)
  • Fluent in English or Spanish
  • Agrees to at least one lumbar puncture for the collection of CSF
  • Willing and able to complete all baseline assessments
  • Willing to undergo repeated MRIs and at least two PET scans and willing to provide DNA and plasma samples as specified
  • Willing and able to participate in a longitudinal imaging study

Specific Inclusion Criteria for follow-up participants from ADNI1:

  • Must have been enrolled and followed in ADNI for at least one year diagnosed as either Mild Cognitive Impairment (MCI) or Cognitively Normal (CN) regardless of whether a diagnostic conversion has occurred since enrolling in ADNI
  • Willing and able to continue to participate in an ongoing longitudinal study; a reduced battery of tests can be requested from the project directors if the participant is not able/willing to complete the full battery
  • Study partner who has frequent contact with participant and can accompany participant to all clinic visits for the duration of the protocol

Exclusion Criteria:

  • 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
  • Screening/baseline MRI scans with evidence of infection, infarction, or other focal lesions; multiple lacunes or lacunes in a critical memory structure
  • 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 DSM-IV within the past 1 year
  • Psychotic features, agitation or behavioral problems within the last 3 months which could lead to difficulty complying with the protocol
  • 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 (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 amyloid imaging with 18F -AV-45: 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
  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: NCT01078636

  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Arizona
Banner Alzheimer's Institute
Phoenix, Arizona, United States, 85006
Banner Sun Health Research Institute
Sun City, Arizona, United States, 85351
United States, California
University of California, Irvine
Irvine, California, United States, 92697
University of California, Irvine - BIC
Irvine, California, United States, 92868
University of Southern California
Los Angeles, California, United States, 90033
University of California, Los Angeles
Los Angeles, California, United States, 90095
University of California, Davis
Martinez, California, United States, 94553
Stanford University
Palo Alto, California, United States, 94304
University of California, San Diego
San Diego, California, United States, 92037
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06510
United States, District of Columbia
Georgetown University
Washington, District of Columbia, United States, 20057
Howard University
Washington, District of Columbia, United States, 20060
United States, Florida
Mayo Clinic, Jacksonville
Jacksonville, Florida, United States, 32224
Wien Center
Miami Beach, Florida, United States, 33140
Premiere Research Institute
West Palm Beach, Florida, United States, 33407
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30329
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
Northwestern University
Chicago, Illinois, United States, 60611
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Kansas
University of Kansas
Kansas City, Kansas, United States, 66160
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21205
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Boston University School of Medicine
Boston, Massachusetts, United States, 02118
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
Mayo Clinic, Rochester
Rochester, Minnesota, United States, 55901
United States, Missouri
Washington University, St. Louis
St. Louis, Missouri, United States, 63108
United States, Nevada
Cleveland Clinic Lou Ruvo Center for Brain Health (CCLRBC)
Las Vegas, Nevada, United States, 89106
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New York
Albany Medical College
Albany, New York, United States, 12208
Dent Neurological Group
Amherst, New York, United States, 14226
New York University
New York, New York, United States, 10016
Columbia University
New York, New York, United States, 10032
Mount Sinai School of Medicine
New York, New York, United States, 10029
University of Rochester Medical Center
Rochester, New York, United States, 14620
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Wake Forest University
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44122
Ohio State University
Columbus, Ohio, United States, 43210
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02903
Butler Hospital Memory & Aging Program
Providence, Rhode Island, United States, 02906
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29406
United States, Texas
University of Texas SWMC
Dallas, Texas, United States, 75390
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53705
Canada, British Columbia
University of British Columbia
Vancouver, British Columbia, Canada, V6T 2B5
Canada, Ontario
Saint Joseph's Hospital
Hamilton, Ontario, Canada, N6A 4V2
Parkwood Hospital
London, Ontario, Canada, N6C 5J1
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
Jewish General Hospital / McGill University
Montreal, Quebec, Canada, H3T 1E2
Sponsors and Collaborators
Alzheimer's Disease Cooperative Study (ADCS)
Northern California Institute of Research and Education
Investigators
Study Chair: Ronald Petersen, MD, PhD Mayo Clinic, Rochester, Minnesota
Principal Investigator: Michael W Weiner, MD University of California, San Francisco
Study Chair: Paul Aisen, MD University of California, San Diego
  More Information

Additional Information:
Publications:
Responsible Party: Alzheimer's Disease Cooperative Study (ADCS)
ClinicalTrials.gov Identifier: NCT01078636     History of Changes
Other Study ID Numbers: IA0175, 1RC2AG036535-01
Study First Received: March 1, 2010
Last Updated: May 15, 2013
Health Authority: United States: Federal Government

Keywords provided by Alzheimer's Disease Cooperative Study (ADCS):
amyloid
plaques
imaging
early detection
Amnestic MCI
pre-dementia

Additional relevant MeSH terms:
Alzheimer Disease
Cognition Disorders
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 July 22, 2014