TRC-PAD Program: In-Clinic Trial-Ready Cohort (TRC-PAD)

Trial Ready Cohort for the Prevention of Alzheimer's Dementia (TRC-PAD)

The purpose of the TRC-PAD study is to develop a large, well-characterized, biomarker-confirmed, trial-ready cohort to facilitate rapid enrollment into AD prevention trials utilizing the APT Webstudy and subsequent referral to in-clinic evaluation and biomarker confirmation. Participants with known biomarker status may have direct referral to the Trial-Ready Cohort.

If you are interested in being selected for the TRC-PAD study, you should first enroll in the APT Webstudy (https://www.aptwebstudy.org/welcome).

Study Overview

• Status: Active, not recruiting
• Conditions: Dementia; Alzheimer Disease; Prodromal Alzheimer's Disease; Preclinical Alzheimer's Disease

Detailed Description

TRC-PAD study is short for the "Trial-Ready Cohort for the Prevention of Alzheimer's Dementia". The purpose of the TRC-PAD study is to find many people (also called a "cohort") who are interested in participating in clinical trials aimed at discovering treatments that will reduce the risk of developing Alzheimer's dementia. TRC-PAD will help researchers enroll participants into these trials quickly to allow new treatments to be discovered as soon as possible.

The TRC-PAD study is for individuals, age 50 and older, who may be at increased risk for memory loss caused by Alzheimer's disease. To join the TRC-PAD study, you first need to be invited to complete an in-person TRC-PAD visit.

How can I be invited to an in-person visit for TRC-PAD? Members of the Alzheimer Prevention Trials (APT) Webstudy complete online questionnaires and memory tests. The results of these tests will identify individuals as being eligible for an in-person TRC-PAD visit. If you are not enrolled in the APT Webstudy, you may be invited to an in-person visit for TRC-PAD because other tests or procedures you have had suggest you might be eligible to participate.

How might the TRC-PAD Study help researchers learn more about Alzheimer's disease dementia? Alzheimer's disease remains one of the most important medical conditions for which there is no treatment. Among the top ten causes of death, Alzheimer's disease is the only one that cannot be prevented, cured, or even slowed. To change this, researchers are conducting clinical trials to find new treatments. These trials need to study large numbers of individuals and follow participants over long periods of time. The goal of TRC-PAD is to identify individuals for these trials. TRC-PAD will find a group of people who may be "at-risk" for developing Alzheimer's dementia in the future and are appropriate for prevention trials.

How does TRC-PAD decide that I may have an increased risk for developing Alzheimer's dementia? A person's risk for developing Alzheimer's dementia is determined by a number of factors including family history, performance on memory tests, and biological tests called biomarkers. Biomarkers are measurements in parts of the body - like blood tests or brain scans - to help assess the presence of, or potential to develop, a disease.

If I decide to join TRC-PAD, what happens? Individuals in the TRC-PAD study will complete several assessments to see if they qualify to join the cohort. This will include biomarker testing (via Positron Emission Tomography (PET) brain scan or spinal fluid collection), tests of memory and thinking, questionnaires about daily functioning, mood and behavior, genetic testing and routine blood and urine tests. Individuals who are determined to eligible to enroll in TRC will come back to the clinic every 6 months for brief longitudinal follow-up visits with questionnaires and testing until that individual qualifies for a clinical trial.

• Study Type: Observational
• Enrollment (Estimated): 2000

Contacts and Locations

• Study Contact: Name: APT / TRC Recruitment Team; Phone Number: 858-877-3135; Email: info@aptwebstudy.org

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University Of Alabama
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner Alzheimer's Institute
    • Sun City, Arizona, United States, 85351
      • Banner Sun Health Research Institute
  • California
    • Irvine, California, United States, 92697
      • University of California, Irvine
    • Los Angeles, California, United States, 90033
      • University of Southern California
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University
  • District of Columbia
    • Washington, District of Columbia, United States, 20057
      • Georgetown University
  • Florida
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
    • Miami, Florida, United States, 33125
      • Gonzalez MD & Aswad MD Health Services
    • Miami Beach, Florida, United States, 33140
      • Wien Center for Alzheimer's Disease
    • Ocala, Florida, United States, 34470
      • Renstar Medical Research
    • Orlando, Florida, United States, 32806
      • Synexus Clinical Research Orlando
    • Tampa, Florida, United States, 33613
      • University of South Florida - Health Byrd Alzheimer Institute
    • The Villages, Florida, United States, 32162-7116
      • Synexus Clinical Research, The Villages
    • Winter Park, Florida, United States, 32792
      • Charter Research, LLC
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • Rush University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • University of Kentucky
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women'S Hospital
    • Plymouth, Massachusetts, United States, 02360
      • Headlands Eastern MA LLC
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic Rochester
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Washington University, St. Louis
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Cleveland Clinic Lou Ruvo Center for Brain Health
  • New York
    • Rochester, New York, United States, 14620
      • University of Rochester Medical Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Beachwood, Ohio, United States, 44195
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Lou Ruvo Center for Brain Health, Cleveland
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Neurological Associates
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
    • Providence, Rhode Island, United States, 02906
      • Butler Hospital Memory and Aging Program
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Ralph H. Johnson VA Medical Center
    • Charleston, South Carolina, United States, 29401
      • Roper St. Francis Hospital
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Fort Worth, Texas, United States, 76107
      • University of North Texas Health Sciences Center
  • Virginia
    • Richmond, Virginia, United States, 23294
      • National Clinical Research, Inc.
  • Washington
    • Seattle, Washington, United States, 98108
      • University of Washington / Seattle Institute for Biomedical and Clinical Research
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin-Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

AD biomarker confirmed individuals who may be at an increased risk for memory loss caused by Alzheimer's disease dementia. Individuals at highest risk within the APT Webstudy will be referred for an in-person TRC-PAD visit. Individuals with known biomarker status may qualify for a direct referral to the trial-ready cohort.

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent form
2. Stated availability and willingness to comply with all study procedures until referred to a clinical trial
3. Age 50-85 (inclusive)
4. Global Clinical Dementia Rating (CDR) score of 0 or 0.5 and no diagnosis of dementia
5. Has a study partner that is willing to participate as a source of information and has at least weekly contact with the participant (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 participant's daily function.
6. In good general health as evidenced by medical history
7. Adequate visual and auditory acuity to allow neuropsychological testing
8. Fluent in English or Spanish
9. For females who are not surgically sterile or post-menopausal by two years, receiving a Positron Emission Tomography (PET) scan for amyloid biomarker confirmation: negative pregnancy test prior to amyloid PET scan
10. Completed six grades of education or has a good work history
11. Evidence of elevated or intermediate (subthreshold) levels brain amyloid as assessed by central review of amyloid PET or cerebrospinal fluid (CSF) data. Prior amyloid testing results may be used with approval from the Coordinating Center.

Exclusion Criteria:

1. Treatment with an another anti-amyloid investigational anti-amyloid drug or other experimental intervention within 12 months. Use of aducanumab or other approved anti-amyloid treatments allowed if stable for at least 3 months.
2. Enrolled in another interventional clinical trial within the last 12 weeks
3. Any significant neurologic disease such as Alzheimer's disease dementia, 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 deficits or known structural brain abnormalities.
4. Major depression, bipolar disorder as described in DSM-V within the past 1 year or psychotic features, agitation or behavioral problems within 3 months, which could lead to difficulty complying with the protocol
5. History of schizophrenia (DSM V criteria)
6. History of alcohol or substance abuse or dependence within the past 2 years (DSM V criteria)
7. Clinically significant or unstable medical condition, including uncontrolled hypertension, uncontrolled diabetes, or significant cardiac, pulmonary, renal, hepatic, endocrine, or other systemic disease in the opinion of the Investigator, may either put the participant at risk because of participation in the study, or influence the results, or the participant's ability to participate in the study.
8. History within the last 3 years of a primary or recurrent malignant disease with the exception of non-melanoma skin cancers, resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with normal prostate-specific antigen post-treatment
9. Clinically significant abnormalities in B12 or thyroid function tests (TFTs) that might interfere with the study. A low B12 is exclusionary, unless follow-up labs (homocysteine (HC) and methylmalonic acid (MMA)) indicate that it is not physiologically significant.
10. Clinically significant abnormalities in screening laboratories or ECG.
11. For participants undergoing CSF collection: a current blood clotting or bleeding disorder, or significantly abnormal PT or PTT at screening or if on anti-coagulation (e.g. warfarin)
12. Participants whom the Site PI deems to be otherwise ineligible.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
TRC-PAD Cohort; Individuals identified as being at an increased risk for memory loss caused by Alzheimer's disease dementia. Determination of risk based on a number of factors including family history, performance on memory tests, genetic tests and biomarker tests.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Enrollment into preclinical and prodromal AD clinical trials	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Optimization of adaptive risk algorithm to predict risk of amyloid positivity	The TRC-PAD program aims to optimize an innovative, adaptive risk algorithm to efficiently identify the most appropriate trial participants. Once optimized, this algorithm will be able to select amyloid positive individuals (and eventually tau and other neurodegenerative biomarkers) with >75% accuracy, greatly reducing future costly biomarker screen fails.	5 years

Collaborators and Investigators

• Sponsor: University of Southern California
• Collaborators: National Institute on Aging (NIA); Alzheimer's Therapeutic Research Institute; Brigham and Women's Hospital; Alzheimer's Clinical Trials Consortium; Cleveland Clinic Lou Ruvo Center for Brain Health
• Investigators: Principal Investigator: Paul Aisen, MD, USC Alzheimer's Therapeutic Research Institute (ATRI); Principal Investigator: Reisa Sperling, MD, Brigham and Women's Hospital; Principal Investigator: Jeffrey Cummings, MD, Cleveland Clinic Lou Ruvo Center for Brain Health

Publications and helpful links

General Publications

• Amariglio RE, Donohue MC, Marshall GA, Rentz DM, Salmon DP, Ferris SH, Karantzoulis S, Aisen PS, Sperling RA; Alzheimer's Disease Cooperative Study. Tracking early decline in cognitive function in older individuals at risk for Alzheimer disease dementia: the Alzheimer's Disease Cooperative Study Cognitive Function Instrument. JAMA Neurol. 2015 Apr;72(4):446-54. doi: 10.1001/jamaneurol.2014.3375. Erratum In: JAMA Neurol. 2015 May;72(5):608.
• Mormino EC, Papp KV, Rentz DM, Donohue MC, Amariglio R, Quiroz YT, Chhatwal J, Marshall GA, Donovan N, Jackson J, Gatchel JR, Hanseeuw BJ, Schultz AP, Aisen PS, Johnson KA, Sperling RA. Early and late change on the preclinical Alzheimer's cognitive composite in clinically normal older individuals with elevated amyloid beta. Alzheimers Dement. 2017 Sep;13(9):1004-1012. doi: 10.1016/j.jalz.2017.01.018. Epub 2017 Feb 28.

Helpful Links

• ATRI Studies
• Alzheimer's Clinical Trials Consortium
• APT Webstudy

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2019
• Primary Completion (Estimated): April 30, 2024
• Study Completion (Estimated): April 30, 2024

Study Registration Dates

• First Submitted: June 28, 2019
• First Submitted That Met QC Criteria: June 28, 2019
• First Posted (Actual): July 2, 2019

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Observational; Prevention; Alzheimer's; Trial-Ready Cohort
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Tauopathies; Dementia; Alzheimer Disease
• Other Study ID Numbers: ATRI-004; R01AG053798 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No