Alzheimer's Disease Neuroimaging Initiative Grand Opportunity

Mild Cognitive Impairment Clinical Trial

— ADNI-GO  

Official title:

Alzheimer's Disease Neuroimaging Initiative Grand Opportunity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01078636
• Other study ID #: IA0175
• Secondary ID: 1RC2AG036535-01
• Status: Completed
• Phase: N/A
• First received: March 1, 2010
• Last updated: September 15, 2014
• Start date: April 2010
• Est. completion date: October 2012

Study information

• Verified date: September 2014
• Source: Alzheimer's Disease Cooperative Study (ADCS)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 342
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 55 Years to 90 Years

Eligibility

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

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease
• Cognition Disorders
• Mild Cognitive Impairment

Locations

Country	Name	City	State
Canada	Saint Joseph's Hospital	Hamilton	Ontario
Canada	Parkwood Hospital	London	Ontario
Canada	Jewish General Hospital / McGill University	Montreal	Quebec
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	University of British Columbia	Vancouver	British Columbia
United States	Albany Medical College	Albany	New York
United States	Dent Neurological Group	Amherst	New York
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Boston University School of Medicine	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	Case Western Reserve University	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	University of Texas SWMC	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of California, Irvine	Irvine	California
United States	University of California, Irvine - BIC	Irvine	California
United States	Mayo Clinic, Jacksonville	Jacksonville	Florida
United States	University of Kansas	Kansas City	Kansas
United States	Cleveland Clinic Lou Ruvo Center for Brain Health (CCLRBC)	Las Vegas	Nevada
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Kentucky	Lexington	Kentucky
United States	University of California, Los Angeles	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	University of Wisconsin	Madison	Wisconsin
United States	University of California, Davis	Martinez	California
United States	Wien Center	Miami Beach	Florida
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Columbia University	New York	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	New York University	New York	New York
United States	Stanford University	Palo Alto	California
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Banner Alzheimer's Institute	Phoenix	Arizona
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Butler Hospital Memory & Aging Program	Providence	Rhode Island
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Mayo Clinic, Rochester	Rochester	Minnesota
United States	University of Rochester Medical Center	Rochester	New York
United States	University of California, San Diego	San Diego	California
United States	University of California, San Francisco	San Francisco	California
United States	Washington University, St. Louis	St. Louis	Missouri
United States	Banner Sun Health Research Institute	Sun City	Arizona
United States	Georgetown University	Washington	District of Columbia
United States	Howard University	Washington	District of Columbia
United States	Premiere Research Institute	West Palm Beach	Florida
United States	Wake Forest University	Winston-Salem	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Alzheimer's Disease Cooperative Study (ADCS)	National Institute on Aging (NIA), Northern California Institute of Research and Education

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (4)

Misra C, Fan Y, Davatzikos C. Baseline and longitudinal patterns of brain atrophy in MCI patients, and their use in prediction of short-term conversion to AD: results from ADNI. Neuroimage. 2009 Feb 15;44(4):1415-22. doi: 10.1016/j.neuroimage.2008.10.031. Epub 2008 Nov 5. — View Citation

Petersen RC, Aisen PS, Beckett LA, Donohue MC, Gamst AC, Harvey DJ, Jack CR Jr, Jagust WJ, Shaw LM, Toga AW, Trojanowski JQ, Weiner MW. Alzheimer's Disease Neuroimaging Initiative (ADNI): clinical characterization. Neurology. 2010 Jan 19;74(3):201-9. doi: 10.1212/WNL.0b013e3181cb3e25. Epub 2009 Dec 30. — View Citation

Risacher SL, Saykin AJ, West JD, Shen L, Firpi HA, McDonald BC; Alzheimer's Disease Neuroimaging Initiative (ADNI). Baseline MRI predictors of conversion from MCI to probable AD in the ADNI cohort. Curr Alzheimer Res. 2009 Aug;6(4):347-61. — View Citation

Shen L, Kim S, Risacher SL, Nho K, Swaminathan S, West JD, Foroud T, Pankratz N, Moore JH, Sloan CD, Huentelman MJ, Craig DW, Dechairo BM, Potkin SG, Jack CR Jr, Weiner MW, Saykin AJ; Alzheimer's Disease Neuroimaging Initiative. Whole genome association study of brain-wide imaging phenotypes for identifying quantitative trait loci in MCI and AD: A study of the ADNI cohort. Neuroimage. 2010 Nov 15;53(3):1051-63. doi: 10.1016/j.neuroimage.2010.01.042. Epub 2010 Jan 25. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Rate of conversion will be evaluated among all four groups		at screening , baseline, 6 (EMCI only) and 12 months	No
Secondary	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)	No
Secondary	Rates of change on each specified biochemical biomarker		at baseline, 6 (EMCI only) and 12 months	No
Secondary	Rates of change of glucose metabolism (FDG-PET)		at baseline	No
Secondary	Extent of amyloid deposition as measured by 18F-AV-45		at baseline	No
Secondary	Group differences for each imaging and biomarker measurement		at screening, baseline, 6 (EMCI only) and 12 months	No
Secondary	Correlations among biomarkers and biomarker change		at screening, baseline, 6 (EMCI only) and 12 months	No
Secondary	Subgroups analyses: APOE genotype, low CSF Aß42, positive amyloid imaging with 18F-AV-45		at baseline	No

External Links

•   ADEAR Center
•   Alzheimer's Disease Cooperative Study, ADNI-GO
•   Laboratory of NeuroImaging: Alzheimer's Disease Neuroimaging Initiative