Longitudinal Evaluation of Amyloid Risk and Neurodegeneration - the LEARN Study

Cognition Disorders Clinical Trial

— LEARN  

Official title:

Longitudinal Evaluation of Amyloid Risk and Neurodegeneration - the LEARN Study. A Companion Observational Study to Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02488720
• Other study ID #: ADC-051
• Secondary ID: U19AG01048315-33
• Status: Completed
• Start date: September 8, 2015
• Est. completion date: September 29, 2023

Study information

• Verified date: November 2023
• Source: University of Southern California
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 538
• Est. completion date: September 29, 2023
• Est. primary completion date: September 29, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 65 Years to 85 Years

Eligibility

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 Aß 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.

Related Conditions & MeSH terms

• Amyloidosis
• Cognition Disorders
• Nerve Degeneration

Locations

Country	Name	City	State
United States	Dent Neurologic Institute	Amherst	New York
United States	University of Michigan, Ann Arbor	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	Case Western Reserve University	Beachwood	Ohio
United States	University of Alabama, Birmingham	Birmingham	Alabama
United States	Boston University	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Roper St. Francis Healthcare	Charleston	South Carolina
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Kansas	Fairway	Kansas
United States	University of Iowa	Iowa City	Iowa
United States	University of California, Irvine	Irvine	California
United States	Mayo Clinic, Jacksonville	Jacksonville	Florida
United States	Cleveland Clinic Lou Ruvo Center for Brain Health	Las Vegas	Nevada
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	Wien Center for Clinical Research	Miami Beach	Florida
United States	Yale University School of Medicine	New Haven	Connecticut
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Synexus Clinical Research	Orlando	Florida
United States	VA Palo Alto HSC / Stanford School of Medicine	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 & Science University	Portland	Oregon
United States	Butler Hospital Memory and 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	Banner Sun Health Research Institute	Sun City	Arizona
United States	University of South Florida - Health Byrd Alzheimer Institute	Tampa	Florida
United States	Synexus Clinical Research - The Villages	The Villages	Florida
United States	Central States Research	Tulsa	Oklahoma
United States	Georgetown University	Washington	District of Columbia
United States	Howard University	Washington	District of Columbia
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (4)

Lead Sponsor	Collaborator
University of Southern California	Alzheimer's Association, Alzheimer's Therapeutic Research Institute, National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View Citation

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):1 — View Citation

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 D — View Citation

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: 10.1 — View Citation

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 pr — View Citation

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)7 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline of the ADCS Preclinical Alzheimer Cognitive Composite (ADCS-PACC) to Week 240		4.5 years
Secondary	Change from Baseline in Cognitive Function Index (CFI) to Week 240		4.5 years
Secondary	Change from Baseline in Mean Composite Summary Uptake Value Ratio (SUVr) to Week 240		4.5 years
Secondary	Change from Baseline in Cerebral Spinal Fluid (CSF) Tau Biomarkers to Week 240		4.5 years
Secondary	Change from Baseline of Cerebrospinal Fluid (CSF) Concentrations of Amyloid Beta (Abeta) to Week 240		4.5 years
Secondary	Change from Baseline of Volumetric Magnetic Resonance Imaging (vMRI) to Week 240		4.5 years

External Links

•   Alzheimer's Therapeutic Research Institute
•   National Institute on Aging