Clinical trial NCT04165109: Trial-Ready Cohort-Down Syndrome (TRC-DS)
Official title: Alzheimer's Clinical Trial Consortium for Down Syndrome (ACTC-DS) Trial-Ready Cohort - Down Syndrome (TRC-DS)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Down Syndrome
Alzheimer Disease
Dementia
Keywords: Trial-Ready Cohort
Observational
Alzheimer's
Prevention
Down Syndrome
Lead sponsor: University of Southern California
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
name: Alzheimer's Clinical Trials Consortium
name: Alzheimer's Therapeutic Research Institute
First posted: 2019-11-15
Enrollment: 450
Sex: ALL
Minimum age (years): 25
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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)

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/.


Eligibility criteria: Inclusion Criteria:

1. 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)
2. 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).
3. 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
4. Male or female, aged 25-55 inclusive
5. In good general health as evidenced by medical history with no diagnosis of dementia
6. 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
7. Adequate visual and auditory acuity to allow neuropsychological testing
8. Mental Age of 4 years or greater (based upon the Kaufman Brief Intelligence Test, Second Edition, or based upon medical records)
9. IQ equal to or greater than 40 (based upon the Kaufman Brief Intelligence Test, Second Edition)
10. Must speak English or Spanish fluently
11. 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

Exclusion Criteria:

1. 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)
2. 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)
3. Participants unable to complete MRI procedure
4. 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
5. Clinically significant abnormalities in B12 or 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. A high TSH is exclusionary unless follow up T3/T4 levels indicate that it is not physiologically significant.
6. Clinically significant abnormalities in screening laboratories
7. 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)
8. 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
9. 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

Primary outcomes:
measure: Enrollment of participants into the Trial-Ready Cohort in DS (TRC-DS).
timeFrame: 5 years
Secondary outcomes:
measure: Change in cognition as measured by the Cued Recall Test
timeFrame: Baseline and Month 32, or until enrollment into a clinical trial
measure: Change in behavior as measured by the Neuropsychiatric Inventory (NPI)
timeFrame: Screening and Month 32, or until enrollment into a clinical trial
measure: Change in cognition as measured by the Down Syndrome Mental Status Exam (DSMSE)
timeFrame: Screening and Month 32, or until enrollment into a clinical trial
measure: Change in behavior as measured by the Vineland 3 (Informant Version)
timeFrame: Baseline and Month 32, or until enrollment into a clinical trial
measure: Change in cognition as measured by the National Task Group Early Detection Screen for Dementia (NTG-EDSD)
timeFrame: Baseline and Month 32, or until enrollment into a clinical trial
measure: Change in cognition as measured by the Stroop Dog and Cat Task
timeFrame: Baseline and Month 32, or until enrollment into a clinical trial
measure: Change in brain volume as measured by magnetic resonance imaging (MRI)
timeFrame: Baseline and Month 32, or until enrollment into a clinical trial
measure: Change in plasma Amyloid Beta (Abeta) biomarkers
timeFrame: Baseline and Month 32, or until enrollment into a clinical trial
measure: Change in plasma tau biomarkers
timeFrame: Baseline and Month 32, or until enrollment into a clinical trial
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Orange
country: United States
facility: University of California, Irvine School of Medicine, Co-Enrolling through ABC-DS Only
state: California
city: Aurora
country: United States
facility: Linda Crnic Institute for Down Syndrome, University of Colorado
state: Colorado
city: Park Ridge
country: United States
facility: Advocate Medical Group Adult Down Syndrome Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky, Co-Enrolling through ABC-DS Only
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital, Co-Enrolling through ABC-DS Only
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University, St. Louis
state: Missouri
city: Staten Island
country: United States
facility: New York State Institute for Basic Research in Developmental Disabilities (SIBRDD), Co-Enrolling through ABC-DS Only
state: New York
city: Beachwood
country: United States
facility: Case Western Reserve University
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh, Co-Enrolling through ABC-DS Only
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center Center for Cognitive Medicine
state: Tennessee
city: San Antonio
country: United States
facility: University of Texas Health San Antonio, Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases
state: Texas
city: Madison
country: United States
facility: University of Wisconsin - Madison, Waisman Center, Co-Enrolling through ABC-DS Only
state: Wisconsin
city: Paris
country: France
facility: Institut Jerome Lejeune
city: Dublin
country: Ireland
facility: Institute of Memory & Cognition, Tallaght University Hospital
city: Barcelona
country: Spain
facility: Sant Pau Biomedical Research Institute (IIB Sant Pau)
city: Cambridge
country: United Kingdom
facility: University of Cambridge, Co-Enrolling through ABC-DS Only
Study officials:
affiliation: USC Alzheimer's Therapeutic Research Institute (ATRI)
name: Michael Rafii, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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.
citation: 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.
citation: 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.
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citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.