Clinical trial NCT00106899: ADNI: Alzheimer's Disease Neuroimaging Initiative
Official title: Alzheimer's Disease Neuroimaging Initiative
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Alzheimer's Disease
Keywords: neuroimaging
brain metabolism
biomarkers
cognition disorder
Mild Cognitive Impairment
Lead sponsor: Alzheimer's Disease Cooperative Study (ADCS)
Sponsor class: OTHER
Collaborators: name: Northern California Institute of Research and Education
name: National Institute on Aging (NIA)
name: National Institute for Biomedical Imaging and Bioengineering (NIBIB)
name: Foundation for the National Institutes of Health
name: Alzheimer's Drug Discovery Foundation
name: Alzheimer's Association
First posted: 2005-04-01
Enrollment: 818
Sex: ALL
Minimum age (years): 55
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: community sample

Brief summary: The purpose of this study is 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). This information will aid future clinical trials by providing a standard assessment tool to measure the effects of treatments being studied.

Detailed description: This study will test whether serial magnetic resonance imaging (MRI), positron emission tomography (PET), other biological markers, and clinical and neuropsychological assessment can be combined to measure the progression of mild cognitive impairment (MCI) and early Alzheimer's disease (AD). The information obtained by studying changes in the brain images of MCI and AD patients and healthy individuals, as well as other assessment tools, will be used to determine the best methods for measuring treatment effects in patients with MCI and AD.

Approximately 800 participants, ranging in age from 55 to 90, will be recruited for the study: 400 patients with MCI, 200 with early AD, and 200 normal controls. Patients with MCI and normal controls will be followed for 3 years, and those with AD will be followed for 2 years. At 6-month intervals, all participants will be seen in person or contacted by telephone. All participants will undergo repeated scanning and blood and urine biomarkers will be collected at the time of each scan. All patients will be asked if they are willing to undergo lumbar puncture at baseline and year one, with the goal of a minimum of 20% and as many as 50% of each group providing CSF (cerebrospinal fluid) samples for analysis and storage for future analyses.

NOTE: Beginning in Spring 2007 a subset of the ADNI participants will be offered the opportunity to participate in a supplemental study. The PIB (Pittsburgh Compound B) study provides imaging of amyloid plaque burden. PIB PET scans will be conducted in 24 control, 48 MCI, and 24 AD participants at approximately 16 ADNI PET sites. For entering participants with no previous PET FDG scans, controls and MCI participants will be scanned with PIB at entry (baseline), 12, 24, and 36 months, and AD participants will be scanned with PIB at entry (baseline), 12, and 24 months. For participants who have undergone previous (baseline and 6 month) PET FDG scans, controls and MCI participants will be scanned with PIB at 12, 24, and 36 months, and AD participants will be scanned with PIB at 12 and 24 months.

Eligibility criteria: Inclusion Criteria:

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

General (applies to each category):

* Between 55 and 90 years of age (Currently, ADNI sites are only recruiting volunteers age 70-90 among people with no memory problems)
* Study partner or caregiver to accompany patient to all scheduled visits
* Fluent in English or Spanish
* Permitted medications stable for at least 4 weeks prior to screening
* Adequate visual and auditory acuity to allow neuropsychological testing
* Good general health with no additional diseases expected to interfere with the study
* Women must be two years post-menopausal or surgically sterile
* Willing and able to complete all baseline assessments, and to participate in the 2-3 year protocol
* Willing to undergo neuroimaging and provide DNA and plasma samples as specified
* Completed 6 grades of education or sufficient work history to exclude mental retardation
* Modified Hachinski score \<=4
* Geriatric Depression Scale \<6

Specific Criteria for MCI and AD patients:

* Memory complaint by patient or study partner
* Abnormal memory function score on Wechsler Memory Scale (adjusted for education)
* Mini-Mental State Exam score between 24 and 30 (MCI) or 20 and 26 (AD)
* Clinical Dementia Rating = 0.5; Memory Box score at least 0.5 (MCI) or 1.0 (AD)

Exclusion Criteria:

* Any significant neurologic disease other than Alzheimer's disease
* Abnormal baseline MRI
* 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, history of schizophrenia
* History of alcohol or substance abuse or dependency within the past 2 years
* Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol
* Clinically significant laboratory abnormalities
* Residence in skilled nursing facility
* Participation in clinical studies involving neuropsychological measures being collected more than one time per year

Specific Exclusion Criteria for MCI and AD:

* Psychotic features, agitation or behavioral problems within the last 3 months which could lead to difficulty complying with the protocol.

Prohibited medications:

* Specific psychoactive medications (for example, certain antidepressants, anti-anxiety medications, sleeping pills, etc.)
* Warfarin (Coumadin)
* Investigational agents

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Banner Good Samaritan Medical Center
state: Arizona
city: Sun City
country: United States
facility: Sun Health / Arizona Consortium
state: Arizona
city: Irvine
country: United States
facility: University of California, Irvine
state: California
city: Irvine
country: United States
facility: University of California, Irvine - Brain Imaging Center
state: California
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Hartford
country: United States
facility: Olin Neuropsychiatry Research Center
state: Connecticut
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Washington
country: United States
facility: Howard University
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic, Jacksonville
state: Florida
city: Miami
country: United States
facility: Wein Center
state: Florida
city: Tampa
country: United States
facility: Byrd Alzheimer's Institute
state: Florida
city: West Palm Beach
country: United States
facility: Premiere Neurological Group
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center/Presbyterian St. Luke's Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston University Schools of Medicine and Public Health
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic, Rochester
state: Minnesota
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: Las Vegas
country: United States
facility: University of Nevada School of Medicine
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Amherst
country: United States
facility: Dent Neurological Institute
state: New York
city: New York
country: United States
facility: New York University
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Orchard Park
country: United States
facility: Dent Neurological Institute
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Syracuse
country: United States
facility: Neurological Care of CNY
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: North Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: London
country: Canada
facility: Parkwood Hospital
state: Ontario
city: London
country: Canada
facility: Saint Joseph's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook and Women's College, Health Sciences Centre, University of Toronto
state: Ontario
city: Montreal
country: Canada
facility: Jewish Hospital Memory Clinic, Quebec
state: Quebec
Study officials:
affiliation: University of California, San Francisco
name: Michael W. Weiner, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic - Rochester, Minnesota
name: Ronald Petersen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Diego
name: Paul Aisen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Frank RA, Galasko D, Hampel H, Hardy J, de Leon MJ, Mehta PD, Rogers J, Siemers E, Trojanowski JQ; National Institute on Aging Biological Markers Working Group. Biological markers for therapeutic trials in Alzheimer's disease. Proceedings of the biological markers working group; NIA initiative on neuroimaging in Alzheimer's disease. Neurobiol Aging. 2003 Jul-Aug;24(4):521-36. doi: 10.1016/s0197-4580(03)00002-2. No abstract available.
citation: Grundman M, Petersen RC, Ferris SH, Thomas RG, Aisen PS, Bennett DA, Foster NL, Jack CR Jr, Galasko DR, Doody R, Kaye J, Sano M, Mohs R, Gauthier S, Kim HT, Jin S, Schultz AN, Schafer K, Mulnard R, van Dyck CH, Mintzer J, Zamrini EY, Cahn-Weiner D, Thal LJ; Alzheimer's Disease Cooperative Study. Mild cognitive impairment can be distinguished from Alzheimer disease and normal aging for clinical trials. Arch Neurol. 2004 Jan;61(1):59-66. doi: 10.1001/archneur.61.1.59.
citation: Petersen RC. Mild cognitive impairment clinical trials. Nat Rev Drug Discov. 2003 Aug;2(8):646-53. doi: 10.1038/nrd1155. No abstract available.
citation: Rouch L, Virecoulon Giudici K, Cantet C, Guyonnet S, Delrieu J, Legrand P, Catheline D, Andrieu S, Weiner M, de Souto Barreto P, Vellas B; Alzheimer's Disease Neuroimaging Initiative. Associations of erythrocyte omega-3 fatty acids with cognition, brain imaging and biomarkers in the Alzheimer's disease neuroimaging initiative: cross-sectional and longitudinal retrospective analyses. Am J Clin Nutr. 2022 Dec 19;116(6):1492-1506. doi: 10.1093/ajcn/nqac236.
citation: Xu G, Zheng S, Zhu Z, Yu X, Jiang J, Jiang J, Chu Z; Alzheimer's Disease Neuroimaging Initiative. Association of tau accumulation and atrophy in mild cognitive impairment: a longitudinal study. Ann Nucl Med. 2020 Nov;34(11):815-823. doi: 10.1007/s12149-020-01506-2. Epub 2020 Aug 12.
citation: Kennedy RE, Schneider LS, Cutter GR; Alzheimer's Disease Neuroimaging Initiative. Biomarker positive and negative subjects in the ADNI cohort: clinical characterization. Curr Alzheimer Res. 2012 Dec;9(10):1135-41. doi: 10.2174/156720512804142976.
citation: Grill JD, Di L, Lu PH, Lee C, Ringman J, Apostolova LG, Chow N, Kohannim O, Cummings JL, Thompson PM, Elashoff D; Alzheimer's Disease Neuroimaging Initiative. Estimating sample sizes for predementia Alzheimer's trials based on the Alzheimer's Disease Neuroimaging Initiative. Neurobiol Aging. 2013 Jan;34(1):62-72. doi: 10.1016/j.neurobiolaging.2012.03.006. Epub 2012 Apr 13.
citation: Schrag A, Schott JM; Alzheimer's Disease Neuroimaging Initiative. What is the clinically relevant change on the ADAS-Cog? J Neurol Neurosurg Psychiatry. 2012 Feb;83(2):171-3. doi: 10.1136/jnnp-2011-300881. Epub 2011 Oct 21.
citation: Samtani MN, Farnum M, Lobanov V, Yang E, Raghavan N, Dibernardo A, Narayan V; Alzheimer's Disease Neuroimaging Initiative. An improved model for disease progression in patients from the Alzheimer's disease neuroimaging initiative. J Clin Pharmacol. 2012 May;52(5):629-44. doi: 10.1177/0091270011405497. Epub 2011 Jun 9.
citation: Schneider LS, Insel PS, Weiner MW; Alzheimer's Disease Neuroimaging Initiative. Treatment with cholinesterase inhibitors and memantine of patients in the Alzheimer's Disease Neuroimaging Initiative. Arch Neurol. 2011 Jan;68(1):58-66. doi: 10.1001/archneurol.2010.343.
citation: Schneider LS, Kennedy RE, Cutter GR; Alzheimer's Disease Neuroimaging Initiative. Requiring an amyloid-beta1-42 biomarker for prodromal Alzheimer's disease or mild cognitive impairment does not lead to more efficient clinical trials. Alzheimers Dement. 2010 Sep;6(5):367-77. doi: 10.1016/j.jalz.2010.07.004.