ADNI-GO: Alzheimer's Disease Neuroimaging Initiative Grand Opportunity

Sponsor

Alzheimer's Disease Cooperative Study (ADCS) (Other)

Overall Status

Completed

CT.gov ID

NCT01078636

Collaborator

Northern California Institute of Research and Education (Other), National Institute on Aging (NIA) (NIH)

342

Enrollment

Locations

Duration (Months)

6.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Mild Cognitive Impairment Alzheimer's Disease

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.

Study Design

Study Type:

Observational

Actual Enrollment :

342 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Alzheimer's Disease Neuroimaging Initiative Grand Opportunity

Study Start Date :

Apr 1, 2010

Actual Primary Completion Date :

Oct 1, 2012

Actual Study Completion Date :

Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

Rate of Decline as measured by: Cognitive tests, Activities of Daily Living, and CDR Sum of Boxes [at screening, baseline, 6 (EMCI only) and 12 months]

Secondary Outcome Measures

Rate of conversion will be evaluated among all four groups [at screening , baseline, 6 (EMCI only) and 12 months]
Rate of volume change of whole brain, hippocampus, and other structural MRI measures [at screening and 3, 6, and 12 months (EMCI); at baseline and 12 months (follow-up patients)]
Rates of change on each specified biochemical biomarker [at baseline, 6 (EMCI only) and 12 months]
Rates of change of glucose metabolism (FDG-PET) [at baseline]
Extent of amyloid deposition as measured by 18F-AV-45 [at baseline]
Group differences for each imaging and biomarker measurement [at screening, baseline, 6 (EMCI only) and 12 months]
Correlations among biomarkers and biomarker change [at screening, baseline, 6 (EMCI only) and 12 months]
Subgroups analyses: APOE genotype, low CSF Aβ42, positive amyloid imaging with 18F-AV-45 [at baseline]

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Banner Alzheimer's Institute	Phoenix	Arizona	United States	85006
3	Banner Sun Health Research Institute	Sun City	Arizona	United States	85351
4	University of California, Irvine	Irvine	California	United States	92697
5	University of California, Irvine - BIC	Irvine	California	United States	92868
6	University of Southern California	Los Angeles	California	United States	90033
7	University of California, Los Angeles	Los Angeles	California	United States	90095
8	University of California, Davis	Martinez	California	United States	94553
9	Stanford University	Palo Alto	California	United States	94304
10	University of California, San Diego	San Diego	California	United States	92037
11	University of California, San Francisco	San Francisco	California	United States	94143
12	Yale University School of Medicine	New Haven	Connecticut	United States	06510
13	Georgetown University	Washington	District of Columbia	United States	20057
14	Howard University	Washington	District of Columbia	United States	20060
15	Mayo Clinic, Jacksonville	Jacksonville	Florida	United States	32224
16	Wien Center	Miami Beach	Florida	United States	33140
17	Premiere Research Institute	West Palm Beach	Florida	United States	33407
18	Emory University	Atlanta	Georgia	United States	30329
19	Northwestern University	Chicago	Illinois	United States	60611
20	Rush University Medical Center	Chicago	Illinois	United States	60612
21	Indiana University	Indianapolis	Indiana	United States	46202
22	University of Kansas	Kansas City	Kansas	United States	66160
23	University of Kentucky	Lexington	Kentucky	United States	40536
24	Johns Hopkins University	Baltimore	Maryland	United States	21205
25	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
26	Boston University School of Medicine	Boston	Massachusetts	United States	02118
27	University of Michigan	Ann Arbor	Michigan	United States	48109
28	Mayo Clinic, Rochester	Rochester	Minnesota	United States	55901
29	Washington University, St. Louis	St. Louis	Missouri	United States	63108
30	Cleveland Clinic Lou Ruvo Center for Brain Health (CCLRBC)	Las Vegas	Nevada	United States	89106
31	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
32	Albany Medical College	Albany	New York	United States	12208
33	Dent Neurological Group	Amherst	New York	United States	14226
34	New York University	New York	New York	United States	10016
35	Mount Sinai School of Medicine	New York	New York	United States	10029
36	Columbia University	New York	New York	United States	10032
37	University of Rochester Medical Center	Rochester	New York	United States	14620
38	Duke University Medical Center	Durham	North Carolina	United States	27710
39	Wake Forest University	Winston-Salem	North Carolina	United States	27157
40	Case Western Reserve University	Cleveland	Ohio	United States	44122
41	Ohio State University	Columbus	Ohio	United States	43210
42	Oregon Health and Science University	Portland	Oregon	United States	97239
43	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
44	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
45	Rhode Island Hospital	Providence	Rhode Island	United States	02903
46	Butler Hospital Memory & Aging Program	Providence	Rhode Island	United States	02906
47	Medical University of South Carolina	Charleston	South Carolina	United States	29406
48	University of Texas SWMC	Dallas	Texas	United States	75390
49	Baylor College of Medicine	Houston	Texas	United States	77030
50	University of Wisconsin	Madison	Wisconsin	United States	53705
51	University of British Columbia	Vancouver	British Columbia	Canada	V6T 2B5
52	Saint Joseph's Hospital	Hamilton	Ontario	Canada	N6A 4V2
53	Parkwood Hospital	London	Ontario	Canada	N6C 5J1
54	Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
55	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
National Institute on Aging (NIA)

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