Clinical trial NCT04004767: TRC-PAD Program: In-Clinic Trial-Ready Cohort
Official title: Trial Ready Cohort for the Prevention of Alzheimer's Dementia (TRC-PAD)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Preclinical Alzheimer's Disease
Prodromal Alzheimer's Disease
Alzheimer Disease
Dementia
Keywords: Alzheimer's
Prevention
Observational
Trial-Ready Cohort
Lead sponsor: University of Southern California
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
name: Alzheimer's Therapeutic Research Institute
name: Alzheimer's Clinical Trials Consortium
name: Brigham and Women's Hospital
name: Cleveland Clinic Lou Ruvo Center for Brain Health
First posted: 2019-07-02
Enrollment: 220
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Enrollment into preclinical and prodromal AD clinical trials
timeFrame: 5 years
Secondary outcomes:
measure: Optimization of adaptive risk algorithm to predict risk of amyloid positivity
timeFrame: 5 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Banner Alzheimer's Institute
state: Arizona
city: Sun City
country: United States
facility: Banner Sun Health Research Institute
state: Arizona
city: Irvine
country: United States
facility: University of California, Irvine
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Delray Beach
country: United States
facility: Brain Matters Research
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Miami Beach
country: United States
facility: Wien Center for Alzheimer's Disease
state: Florida
city: Miami
country: United States
facility: Gonzalez MD & Aswad MD Health Services
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Orlando
country: United States
facility: Synexus Clinical Research Orlando
state: Florida
city: Tampa
country: United States
facility: University of South Florida - Health Byrd Alzheimer Institute
state: Florida
city: The Villages
country: United States
facility: Synexus Clinical Research, The Villages
state: Florida
city: Winter Park
country: United States
facility: Charter Research, LLC
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Fairway
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 & Women's Hospital
state: Massachusetts
city: Plymouth
country: United States
facility: Headlands Eastern MA LLC
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: Saint Louis
country: United States
facility: Washington University, St. Louis
state: Missouri
city: Las Vegas
country: United States
facility: Cleveland Clinic Lou Ruvo Center for Brain Health
state: Nevada
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Beachwood
country: United States
facility: Case Western Reserve University
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Lou Ruvo Center for Brain Health, Cleveland
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Abington
country: United States
facility: Abington Neurological Associates
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Providence
country: United States
facility: Butler Hospital Memory and Aging Program
state: Rhode Island
city: Charleston
country: United States
facility: Ralph H. Johnson VA Medical Center
state: South Carolina
city: Charleston
country: United States
facility: Roper St. Francis Hospital
state: South Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Fort Worth
country: United States
facility: University of North Texas Health Sciences Center
state: Texas
city: Richmond
country: United States
facility: National Clinical Research, Inc.
state: Virginia
city: Seattle
country: United States
facility: University of Washington / Seattle Institute for Biomedical and Clinical Research
state: Washington
city: Madison
country: United States
facility: University of Wisconsin-Madison
state: Wisconsin
Study officials:
affiliation: USC Alzheimer's Therapeutic Research Institute (ATRI)
name: Paul Aisen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brigham and Women's Hospital
name: Reisa Sperling, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cleveland Clinic Lou Ruvo Center for Brain Health
name: Jeffrey Cummings, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.