Trial-Ready Cohort-Down Syndrome (TRC-DS)

NCT04165109 | Recruiting DMC

• 2 other identifiers: ATRI-0061R61AG066543-01
• Study Type: observational
• Target: 450
• Locations: 5 countries
• Sites: 20

Brief Summary

The purpose of the Trial-Ready Cohort - Down Syndrome (TRC-DS) is to enroll 120 healthy adults with Down syndrome (DS), between the ages of 25-55, into a trial ready cohort (TRC), and up to 450 participants in total including co-enrolled in the Alzheimer Biomarkers Consortium - Down Syndrome (ABC-DS) study. Participants enrolled in the TRC-DS will undergo longitudinal cognitive and clinical assessment, genetic and biomarker testing, as well as imaging and biospecimen collection. Using these outcome measures, researchers will analyze the relationships between cognitive measures and biomarkers of Alzheimer's disease (AD) to identify endpoints for AD clinical trials in DS that best reflect disease progression. To learn more about the study and participating sites, visit our study website at: https://www.trcds.org/. TRC-DS is collaborating with the Alzheimer's Disease Biomarker Consortium-Down Syndrome (ABC-DS) to allow study participants to be concurrently enrolled in both ABC-DS and TRC-DS, referred to as "co-enrollment". ABC-DS is a longitudinal, observational research study that is overseen at University of Pittsburgh Coordinating Center. ABC-DS participants who express interest in potentially joining a clinical trial in the future and who meet TRC-DS eligibility criteria, may choose to co-enroll in TRC-DS at an ABC-DS Site. Co-enrolled participants will adhere to the ABC-DS protocol and schedule of activities, but agree to share their data with the TRC-DS team and to receive invitations for future participation in clinical trials. Fore more information on ABC-DS please visit https://www.nia.nih.gov/research/abc-ds or http://abcds.pitt.edu/.

Conditions

Down Syndrome; Alzheimer Disease; Dementia

Keywords

Trial-Ready Cohort; Observational; Alzheimer's; Prevention; Down Syndrome

Outcome Measures

Primary Outcomes (1)

• Enrollment of participants into the Trial-Ready Cohort in DS (TRC-DS).

  The primary aim of the TRC-DS is enrollment of 120 participants into the trial ready cohort, with up to 450 participants in total including co-enrollment with the Alzheimer Biomarkers Consortium - Down Syndrome (ABC-DS) study, to support future referral and enrollment into primary Alzheimer's disease (AD) prevention trials for adults with DS.

  5 years

Secondary Outcomes (9)

• Change in cognition as measured by the Cued Recall Test

  Baseline and Month 32, or until enrollment into a clinical trial

• Change in behavior as measured by the Neuropsychiatric Inventory (NPI)

  Screening and Month 32, or until enrollment into a clinical trial

• Change in cognition as measured by the Down Syndrome Mental Status Exam (DSMSE)

  Screening and Month 32, or until enrollment into a clinical trial

• Change in behavior as measured by the Vineland 3 (Informant Version)

  Baseline and Month 32, or until enrollment into a clinical trial

• Change in cognition as measured by the National Task Group Early Detection Screen for Dementia (NTG-EDSD)

  Baseline and Month 32, or until enrollment into a clinical trial

Study Arms (1)

Trial Ready Cohort

Non-demented adults with Down syndrome (DS)

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

120 non-demented adults with Down Syndrome and up to 450 participants in total including co-enrollment the Alzheimer Biomarkers Consortium - Down Syndrome (ABC-DS)

You may qualify if:

• Diagnosis of DS (including trisomy 21, mosaic trisomy 21, Robertsonian translocation trisomy 21 or partial trisomy 21) (as confirmed by Karyotype genetic testing or medical record review)
• Provision of signed and dated informed consent form; this includes adults with DS who can provide consent, or for whom an LAR provides consent on behalf of the individual to participate. Adults with DS who cannot consent must sign and date an assent accompanied with a signed and dated consent by legally authorized representative (LAR).
• Stated availability and willingness to comply with all study procedures and availability for the duration of the study or until referred to a clinical trial
• Male or female, aged 25-55 inclusive
• In good general health as evidenced by medical history with no diagnosis of dementia
• Permitted CNS-active medications, stable in dose for at least 4 weeks or longer. If new medications have been started, medical monitoring team will review on case by case basis to recommend timing of baseline cognitive testing
• Adequate visual and auditory acuity to allow neuropsychological testing
• Mental Age of 4 years or greater (based upon the Kaufman Brief Intelligence Test, Second Edition, or based upon medical records)
• IQ equal to or greater than 40 (based upon the Kaufman Brief Intelligence Test, Second Edition)
• Must speak English or Spanish fluently
• Must have a reliable Study Partner (may be caregiver, sibling, parent) who is capable of providing correct information about the participant's clinical symptoms and history

You may not qualify if:

• Any significant disease or unstable medical condition that could affect participation (i.e., unstable psychiatric disease, unstable cardiac problems, chronic renal failure, chronic hepatic disease, severe pulmonary disease)
• Participants in whom magnetic resonance imaging (MRI) is contraindicated including, but not limited to, those with a pacemaker, presence of metallic fragments near the eyes or spinal cord, or cochlear implant (Dental fillings do not present a risk for MRI)
• Participants unable to complete MRI procedure
• History, within the last 5 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
• Clinically significant abnormalities in screening laboratories
• 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 therapy (e.g. warfarin)
• Concurrent participation in a clinical trial for an investigational product or concurrent participation in longitudinal study with overlapping outcome measures/procedures is prohibited with the exception of ABC-DS co-enrollment or as approved by project director
• Participants whom the investigator deems to be otherwise ineligible. The Investigators should consult with the Coordinating Center on any issues that may disqualify the participant from participation in future clinical trials to determine whether enrollment into TRC-DS would be appropriate

Sponsors & Collaborators

• University of Southern California: lead
• National Institute on Aging (NIA): collaborator
• Alzheimer's Clinical Trials Consortium: collaborator
• Alzheimer's Therapeutic Research Institute: collaborator

Study Sites (20)

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

RECRUITING

University of California, Irvine School of Medicine, Co-Enrolling through ABC-DS Only

Orange, California, 92868, United States

RECRUITING

Linda Crnic Institute for Down Syndrome, University of Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Advocate Medical Group Adult Down Syndrome Center

Park Ridge, Illinois, 60068, United States

NOT YET RECRUITING

Indiana University

Indianapolis, Indiana, 46202, United States

RECRUITING

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

RECRUITING

University of Kentucky, Co-Enrolling through ABC-DS Only

Lexington, Kentucky, 40504, United States

RECRUITING

Massachusetts General Hospital, Co-Enrolling through ABC-DS Only

Boston, Massachusetts, 02114, United States

RECRUITING

Washington University, St. Louis

St Louis, Missouri, 63108, United States

RECRUITING

New York State Institute for Basic Research in Developmental Disabilities (SIBRDD), Co-Enrolling through ABC-DS Only

Staten Island, New York, 10314, United States

RECRUITING

Case Western Reserve University

Beachwood, Ohio, 44122, United States

RECRUITING

University of Cincinnati

Cincinnati, Ohio, 45219, United States

NOT YET RECRUITING

University of Pittsburgh, Co-Enrolling through ABC-DS Only

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Vanderbilt University Medical Center Center for Cognitive Medicine

Nashville, Tennessee, 37212, United States

RECRUITING

University of Texas Health San Antonio, Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases

San Antonio, Texas, 78229, United States

RECRUITING

University of Wisconsin - Madison, Waisman Center, Co-Enrolling through ABC-DS Only

Madison, Wisconsin, 53705, United States

RECRUITING

Institut Jerome Lejeune

Paris, France, 75018, France

RECRUITING

Institute of Memory & Cognition, Tallaght University Hospital

Dublin, Ireland, 24, Ireland

RECRUITING

Sant Pau Biomedical Research Institute (IIB Sant Pau)

Barcelona, 08041, Spain

RECRUITING

University of Cambridge, Co-Enrolling through ABC-DS Only

Cambridge, CB2 1TN, United Kingdom

RECRUITING

Related Publications (10)

• Hardy J. The discovery of Alzheimer-causing mutations in the APP gene and the formulation of the "amyloid cascade hypothesis". FEBS J. 2017 Apr;284(7):1040-1044. doi: 10.1111/febs.14004.

  PMID: 28054745 BACKGROUND

• Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol Med. 2016 Jun 1;8(6):595-608. doi: 10.15252/emmm.201606210. Print 2016 Jun.

  PMID: 27025652 BACKGROUND

• Handen BL, Cohen AD, Channamalappa U, Bulova P, Cannon SA, Cohen WI, Mathis CA, Price JC, Klunk WE. Imaging brain amyloid in nondemented young adults with Down syndrome using Pittsburgh compound B. Alzheimers Dement. 2012 Nov;8(6):496-501. doi: 10.1016/j.jalz.2011.09.229.

  PMID: 23102120 BACKGROUND

• Rafii MS, Wishnek H, Brewer JB, Donohue MC, Ness S, Mobley WC, Aisen PS, Rissman RA. The down syndrome biomarker initiative (DSBI) pilot: proof of concept for deep phenotyping of Alzheimer's disease biomarkers in down syndrome. Front Behav Neurosci. 2015 Sep 14;9:239. doi: 10.3389/fnbeh.2015.00239. eCollection 2015.

  PMID: 26441570 BACKGROUND

• Lao PJ, Betthauser TJ, Hillmer AT, Price JC, Klunk WE, Mihaila I, Higgins AT, Bulova PD, Hartley SL, Hardison R, Tumuluru RV, Murali D, Mathis CA, Cohen AD, Barnhart TE, Devenny DA, Mailick MR, Johnson SC, Handen BL, Christian BT. The effects of normal aging on amyloid-beta deposition in nondemented adults with Down syndrome as imaged by carbon 11-labeled Pittsburgh compound B. Alzheimers Dement. 2016 Apr;12(4):380-90. doi: 10.1016/j.jalz.2015.05.013. Epub 2015 Jun 13.

  PMID: 26079411 BACKGROUND

• Rafii MS, Lukic AS, Andrews RD, Brewer J, Rissman RA, Strother SC, Wernick MN, Pennington C, Mobley WC, Ness S, Matthews DC; Down Syndrome Biomarker Initiative and the Alzheimer's Disease Neuroimaging Initiative. PET Imaging of Tau Pathology and Relationship to Amyloid, Longitudinal MRI, and Cognitive Change in Down Syndrome: Results from the Down Syndrome Biomarker Initiative (DSBI). J Alzheimers Dis. 2017;60(2):439-450. doi: 10.3233/JAD-170390.

  PMID: 28946567 BACKGROUND

• McCarron M, McCallion P, Reilly E, Dunne P, Carroll R, Mulryan N. A prospective 20-year longitudinal follow-up of dementia in persons with Down syndrome. J Intellect Disabil Res. 2017 Sep;61(9):843-852. doi: 10.1111/jir.12390. Epub 2017 Jun 29.

  PMID: 28664561 BACKGROUND

• Firth NC, Startin CM, Hithersay R, Hamburg S, Wijeratne PA, Mok KY, Hardy J, Alexander DC; LonDownS Consortium; Strydom A. Aging related cognitive changes associated with Alzheimer's disease in Down syndrome. Ann Clin Transl Neurol. 2018 May 20;5(6):741-751. doi: 10.1002/acn3.571. eCollection 2018 Jun.

  PMID: 29928657 BACKGROUND

• Startin CM, Hamburg S, Hithersay R, Al-Janabi T, Mok KY, Hardy J; LonDownS Consortium; Strydom A. Cognitive markers of preclinical and prodromal Alzheimer's disease in Down syndrome. Alzheimers Dement. 2019 Feb;15(2):245-257. doi: 10.1016/j.jalz.2018.08.009. Epub 2018 Nov 28.

  PMID: 30503169 BACKGROUND

• Hithersay R, Startin CM, Hamburg S, Mok KY, Hardy J, Fisher EMC, Tybulewicz VLJ, Nizetic D, Strydom A. Association of Dementia With Mortality Among Adults With Down Syndrome Older Than 35 Years. JAMA Neurol. 2019 Feb 1;76(2):152-160. doi: 10.1001/jamaneurol.2018.3616.

  PMID: 30452522 BACKGROUND

Related Links

• ATRI Studies
• Alzheimer's Clinical Trials Consortium
• The INCLUDE Project
• Alzheimer's Clinical Trials Consortium - Down syndrome
• Trial Ready Cohort-Down Syndrome

Biospecimen

Retention: SAMPLES WITH DNA

Blood, Urine, CSF

MeSH Terms

Conditions

Down Syndrome; Alzheimer Disease; Dementia

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Michael Rafii, MD, PhD

  USC Alzheimer's Therapeutic Research Institute (ATRI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

ATRI Recruitment Team

CONTACT

213-821-0569; atri-recruit@usc.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 25, 2019
• First Posted: November 15, 2019
• Study Start: June 7, 2021
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: June 4, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

IE (1); FR (1); ES (1); GB (1); US (16)