Longitudinal Evaluation of Amyloid Risk and Neurodegeneration - the LEARN Study

NCT ID: NCT02488720

Last Updated: 2023-11-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

538 participants

Study Classification

OBSERVATIONAL

Study Start Date

2015-09-08

Study Completion Date

2023-09-29

Brief Summary

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The LEARN study a multicenter, observational study will that will evaluate the rate of cognitive change in approximately 500 clinically normal older individuals who "screen-fail" for the A4 trial on the basis of their screening PET imaging not demonstrating evidence of elevated amyloid accumulation (Aβ negative) but meet all other A4 study eligibility criteria. This study will leverage the A4 infrastructure and maximize the data acquired in screening a large number of well-characterized older adults for the A4 trial.

The LEARN observational cohort will provide a critical comparison group for the A4 placebo arm, and future trials in preclinical AD. Although accumulating longitudinal data suggest that older individuals with elevated Aβ burden are at increased risk of cognitive decline, it is important to demonstrate a differential rate of clinical decline between Aβe ("Aβ elevated") and Aβne ("Aβ not elevated") individuals on a standardized set of clinical outcomes. Over 2000 well-characterized, highly motivated older volunteers will "screen fail" for the A4 trial. The LEARN study will follow 500 of these individuals, matched as closely as possible to the two treatment arms, in this observation cohort. The LEARN study may selectively recruit from a specific range of SUVr that fall below the threshold for "elevated amyloid" in order to support analyses of the relationship of baseline SUVr to subsequent cognitive change and amyloid accumulation. The observational cohort will be followed for 384 weeks with identical clinical/cognitive testing performed every 24 weeks, running parallel to the A4 treatment study and open label extension.

Detailed Description

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Conditions

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Cognition Disorders

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Clinically normal older inviduals

500 clinically normal older individuals with florbetapir positron emission tomography (PET) scan that does not show evidence of brain amyloid pathology at screening.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

1. Consented to participate in the A4 study and previously met A4 demographic, cognitive and clinical criteria (e.g., Mini-Mental State Examination (MMSE); Clinical Dementia Ratin (CDR); Logical Memory test, part IIa (LMIIa); medications; medical history).
2. Has a florbetapir PET scan that falls below the Aβ threshold levels required for randomization into the treatment arms of the A4 trial.
3. In general, permitted medications should be stable for 8 weeks prior to LEARN Visit 1. Changes to medications that, in the opinion of the investigator, are not likely to impact LEARN Visit 1 assessments are permissible.
4. Has a study partner that is willing to participate as a source of information and has at least weekly contact with the subject (contact can be in-person, via telephone or electronic communication). The study partner must have sufficient contact such that the investigator feels the study partner can provide meaningful information about the subject's daily function.
5. In the investigator's opinion, is both willing and able to participate in all required procedures for the duration of the study (at least 240 weeks), including adequate literacy in English or Spanish and adequate vision and hearing to complete the required psychometric tests.

Exclusion Criteria

1. Is receiving a prescription acetylcholinesterase inhibitor (AChEI) and/or memantine at LEARN Visit 1
2. Has current serious or unstable illness including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic, psychiatric, immunologic, or hematologic disease or other conditions that, in the investigator's opinion, could interfere with the analyses of safety and efficacy in this study.
3. Has any contraindications for MRI studies, including claustrophobia, the presence of metal (ferromagnetic) implants, or a cardiac pacemaker that is not compatible with MRI.
4. Has a LEARN Visit 1 MRI scan with results showing \>4 hemosiderin deposits (definite microhemorrhages or areas of superficial siderosis); or any amyloid-related imaging abnormalities - edema/effusions (ARIA-E).
5. Has received any exclusionary medication, including those with significant central nervous system (CNS) anticholinergic effects, within 3 months prior to LEARN Visit 1 or initiated at any point after screen. A full list of exclusionary medication will be provided in the relevant procedures manual.
6. Is currently enrolled in a clinical trial involving an investigational product or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. Participation in observational studies may be permitted upon review of the observational study protocol and approval by the Project Director or one of the ADCS Medical Monitors.

For subjects participating in the optional Lumbar Puncture (LP, all of the above, plus:
7. Current use of anticoagulants, such as warfarin or dabigatran.
Minimum Eligible Age

65 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Alzheimer's Association

OTHER

Sponsor Role collaborator

National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

Alzheimer's Therapeutic Research Institute

OTHER

Sponsor Role collaborator

University of Southern California

OTHER

Sponsor Role lead

Responsible Party

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Paul Aisen

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Reisa Sperling, MD

Role: STUDY_DIRECTOR

Center for Alzheimer Research and Treatment Brigham and Women's Hospital

Locations

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University of Alabama, Birmingham

Birmingham, Alabama, United States

Site Status

Banner Alzheimer's Institute

Phoenix, Arizona, United States

Site Status

Banner Sun Health Research Institute

Sun City, Arizona, United States

Site Status

University of California, Irvine

Irvine, California, United States

Site Status

University of Southern California

Los Angeles, California, United States

Site Status

University of California, Los Angeles

Los Angeles, California, United States

Site Status

VA Palo Alto HSC / Stanford School of Medicine

Palo Alto, California, United States

Site Status

Yale University School of Medicine

New Haven, Connecticut, United States

Site Status

Georgetown University

Washington D.C., District of Columbia, United States

Site Status

Howard University

Washington D.C., District of Columbia, United States

Site Status

Mayo Clinic, Jacksonville

Jacksonville, Florida, United States

Site Status

Wien Center for Clinical Research

Miami Beach, Florida, United States

Site Status

Synexus Clinical Research

Orlando, Florida, United States

Site Status

University of South Florida - Health Byrd Alzheimer Institute

Tampa, Florida, United States

Site Status

Synexus Clinical Research - The Villages

The Villages, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

University of Iowa

Iowa City, Iowa, United States

Site Status

University of Kansas

Fairway, Kansas, United States

Site Status

University of Kentucky

Lexington, Kentucky, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Boston University

Boston, Massachusetts, United States

Site Status

University of Michigan, Ann Arbor

Ann Arbor, Michigan, United States

Site Status

Mayo Clinic, Rochester

Rochester, Minnesota, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Cleveland Clinic Lou Ruvo Center for Brain Health

Las Vegas, Nevada, United States

Site Status

Dent Neurologic Institute

Amherst, New York, United States

Site Status

University of Rochester Medical Center

Rochester, New York, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

Case Western Reserve University

Beachwood, Ohio, United States

Site Status

Central States Research

Tulsa, Oklahoma, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Butler Hospital Memory and Aging Program

Providence, Rhode Island, United States

Site Status

Roper St. Francis Healthcare

Charleston, South Carolina, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

Countries

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United States

References

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Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, Iwatsubo T, Jack CR Jr, Kaye J, Montine TJ, Park DC, Reiman EM, Rowe CC, Siemers E, Stern Y, Yaffe K, Carrillo MC, Thies B, Morrison-Bogorad M, Wagster MV, Phelps CH. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):280-92. doi: 10.1016/j.jalz.2011.03.003. Epub 2011 Apr 21.

Reference Type RESULT
PMID: 21514248 (View on PubMed)

Vos SJ, Xiong C, Visser PJ, Jasielec MS, Hassenstab J, Grant EA, Cairns NJ, Morris JC, Holtzman DM, Fagan AM. Preclinical Alzheimer's disease and its outcome: a longitudinal cohort study. Lancet Neurol. 2013 Oct;12(10):957-65. doi: 10.1016/S1474-4422(13)70194-7. Epub 2013 Sep 4.

Reference Type RESULT
PMID: 24012374 (View on PubMed)

Jack CR Jr, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, Petersen RC, Trojanowski JQ. Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol. 2010 Jan;9(1):119-28. doi: 10.1016/S1474-4422(09)70299-6.

Reference Type RESULT
PMID: 20083042 (View on PubMed)

Mormino EC, Betensky RA, Hedden T, Schultz AP, Amariglio RE, Rentz DM, Johnson KA, Sperling RA. Synergistic effect of beta-amyloid and neurodegeneration on cognitive decline in clinically normal individuals. JAMA Neurol. 2014 Nov;71(11):1379-85. doi: 10.1001/jamaneurol.2014.2031.

Reference Type RESULT
PMID: 25222039 (View on PubMed)

Knopman DS, Jack CR Jr, Wiste HJ, Weigand SD, Vemuri P, Lowe V, Kantarci K, Gunter JL, Senjem ML, Ivnik RJ, Roberts RO, Boeve BF, Petersen RC. Short-term clinical outcomes for stages of NIA-AA preclinical Alzheimer disease. Neurology. 2012 May 15;78(20):1576-82. doi: 10.1212/WNL.0b013e3182563bbe. Epub 2012 May 2.

Reference Type RESULT
PMID: 22551733 (View on PubMed)

Lim YY, Pietrzak RH, Ellis KA, Jaeger J, Harrington K, Ashwood T, Szoeke C, Martins RN, Bush AI, Masters CL, Rowe CC, Villemagne VL, Ames D, Darby D, Maruff P. Rapid decline in episodic memory in healthy older adults with high amyloid-beta. J Alzheimers Dis. 2013;33(3):675-9. doi: 10.3233/JAD-2012-121516.

Reference Type RESULT
PMID: 23001710 (View on PubMed)

Dubbelman MA, Liu A, Donohue MC, Langford O, Raman R, Rentz DM, Amariglio R, Sperling RA, Aisen PS, Marshall GA; as the A4 Study team. Changes in Daily Functioning in Association With Tau and Amyloid Among Unimpaired Older Adults With and Without Elevated Amyloid. Neurology. 2025 Jun 24;104(12):e213775. doi: 10.1212/WNL.0000000000213775. Epub 2025 May 29.

Reference Type DERIVED
PMID: 40440591 (View on PubMed)

Related Links

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https://keck.usc.edu/atri/research/studies/

Alzheimer's Therapeutic Research Institute

Other Identifiers

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U19AG010483

Identifier Type: NIH

Identifier Source: secondary_id

View Link

15-338729

Identifier Type: OTHER

Identifier Source: secondary_id

ADC-051

Identifier Type: -

Identifier Source: org_study_id

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