Longitudinal Evaluation of Amyloid Risk and Neurodegeneration - the LEARN Study

Sponsor

University of Southern California (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02488720

Collaborator

Alzheimer's Association (Other), National Institute on Aging (NIA) (NIH), Alzheimer's Therapeutic Research Institute (Other)

500

Enrollment

Locations

81.7

Anticipated Duration (Months)

12.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Cognition Disorders

Study Design

Study Type:

Observational

Anticipated Enrollment :

500 participants

Observational Model:

Cohort

Time Perspective:

Prospective

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

Actual Study Start Date :

Sep 8, 2015

Anticipated Primary Completion Date :

Jul 1, 2022

Anticipated Study Completion Date :

Jul 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
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.

Outcome Measures

Primary Outcome Measures

Change from Baseline of the ADCS Preclinical Alzheimer Cognitive Composite (ADCS-PACC) to Week 240 [4.5 years]

Secondary Outcome Measures

Change from Baseline in Cognitive Function Index (CFI) to Week 240 [4.5 years]
Change from Baseline in Mean Composite Summary Uptake Value Ratio (SUVr) to Week 240 [4.5 years]
Change from Baseline in Cerebral Spinal Fluid (CSF) Tau Biomarkers to Week 240 [4.5 years]
Change from Baseline of Cerebrospinal Fluid (CSF) Concentrations of Amyloid Beta (Abeta) to Week 240 [4.5 years]
Change from Baseline of Volumetric Magnetic Resonance Imaging (vMRI) to Week 240 [4.5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

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).
Has a florbetapir PET scan that falls below the Aβ threshold levels required for randomization into the treatment arms of the A4 trial.
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.
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.
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:

Is receiving a prescription acetylcholinesterase inhibitor (AChEI) and/or memantine at LEARN Visit 1
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.
Has any contraindications for MRI studies, including claustrophobia, the presence of metal (ferromagnetic) implants, or a cardiac pacemaker that is not compatible with MRI.
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).
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.
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:

Current use of anticoagulants, such as warfarin or dabigatran.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama, 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 Southern California	Los Angeles	California	United States	90033
6	University of California, Los Angeles	Los Angeles	California	United States	90095
7	VA Palo Alto HSC / Stanford School of Medicine	Palo Alto	California	United States	94304
8	Yale University School of Medicine	New Haven	Connecticut	United States	06510
9	Georgetown University	Washington	District of Columbia	United States	20057
10	Howard University	Washington	District of Columbia	United States	20060
11	Mayo Clinic, Jacksonville	Jacksonville	Florida	United States	32224
12	Wien Center for Clinical Research	Miami Beach	Florida	United States	33140
13	Synexus Clinical Research	Orlando	Florida	United States	32806
14	University of South Florida - Health Byrd Alzheimer Institute	Tampa	Florida	United States	33613
15	Synexus Clinical Research - The Villages	The Villages	Florida	United States	32162
16	Emory University	Atlanta	Georgia	United States	30322
17	Northwestern University	Chicago	Illinois	United States	60611
18	Rush University Medical Center	Chicago	Illinois	United States	60612
19	University of Iowa	Iowa City	Iowa	United States	52242
20	University of Kansas	Fairway	Kansas	United States	66205
21	University of Kentucky	Lexington	Kentucky	United States	40504
22	Johns Hopkins University	Baltimore	Maryland	United States	21224
23	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
24	Boston University	Boston	Massachusetts	United States	02118
25	University of Michigan, Ann Arbor	Ann Arbor	Michigan	United States	48105
26	Mayo Clinic, Rochester	Rochester	Minnesota	United States	55905
27	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
28	Cleveland Clinic Lou Ruvo Center for Brain Health	Las Vegas	Nevada	United States	89106
29	Dent Neurologic Institute	Amherst	New York	United States	14226
30	University of Rochester Medical Center	Rochester	New York	United States	14620
31	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
32	Case Western Reserve University	Beachwood	Ohio	United States	44122
33	Central States Research	Tulsa	Oklahoma	United States	74104
34	Oregon Health & Science University	Portland	Oregon	United States	97239
35	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104-2676
36	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
37	Rhode Island Hospital	Providence	Rhode Island	United States	02903
38	Butler Hospital Memory and Aging Program	Providence	Rhode Island	United States	02906
39	Roper St. Francis Healthcare	Charleston	South Carolina	United States	29414
40	University of Wisconsin	Madison	Wisconsin	United States	53792