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

Официальное название

Alzheimer's Clinical Trial Consortium for Down Syndrome (ACTC-DS) Trial-Ready Cohort - Down Syndrome (TRC-DS)

Обзор

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 550 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/.

Первичные конечные точки

• Enrollment of participants into the Trial-Ready Cohort in DS (TRC-DS). [Срок оценки: 5 years]

Вторичные конечные точки (10)

• Change in cognition as measured by the Modified Cued Recall Test [Срок оценки: Baseline and Month 48 or until enrollment into a clinical trial]
• Change in behavior as measured by the Neuropsychiatric Inventory (NPI) [Срок оценки: Screening and Month 48, or until enrollment into a clinical trial]
• Change in cognition as measured by the Down Syndrome Mental Status Exam (DSMSE) [Срок оценки: Screening and Month 48, or until enrollment into a clinical trial]
• Change in behavior as measured by the Vineland 3 (Informant Version) [Срок оценки: Baseline and Month 48, or until enrollment into a clinical trial]
• Change in cognition as measured by the National Task Group Early Detection Screen for Dementia (NTG-EDSD) [Срок оценки: Baseline and Month 48, or until enrollment into a clinical trial]
• Change in cognition as measured by the Stroop Dog and Cat Task [Срок оценки: Baseline and Month 48, or until enrollment into a clinical trial]
• Clinical Global Impression of Change in Down Syndrome (CGIC-DS) [Срок оценки: Baseline and Month 48 or until enrollment into a clinical trial]
• Change in brain volume as measured by magnetic resonance imaging (MRI) [Срок оценки: Baseline and Month 48, or until enrollment into a clinical trial]
• Change in plasma Amyloid Beta (Abeta) biomarkers [Срок оценки: Baseline and Month 48, or until enrollment into a clinical trial]
• Change in plasma tau biomarkers [Срок оценки: Baseline and Month 48, or until enrollment into a clinical trial]

Критерии участия

Критерии включения

• Diagnosis of DS (including trisomy 21, mosaic trisomy 21, Robertsonian translocation trisomy 21 or partial trisomy 21) (as confirmed by 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, KBIT-2, verbal age equivalent, or based upon medical records)
• Ability to complete KBIT-2 with IQ equal to or greater than 40
• 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

Критерии исключения

• 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 non-compatible pacemaker, presence of MRI-incompatible 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 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.
• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

США · 18 центров

• Barrow Neurological Institute — Phoenix
• University of California, Irvine School of Medicine, Co-Enrolling through ABC-DS Only — Orange
• Linda Crnic Institute for Down Syndrome, University of Colorado — Aurora
• Advocate Medical Group Adult Down Syndrome Center — Park Ridge
• Indiana University — Indianapolis
• University of Kansas Medical Center — Kansas City
• University of Kentucky, Co-Enrolling through ABC-DS Only — Lexington
• Massachusetts General Hospital, Co-Enrolling through ABC-DS Only — Boston
• … и ещё 10 центров

Франция · 1 центр

• Institut Jerome Lejeune — Paris

Ирландия · 1 центр

• Institute of Memory & Cognition, Tallaght University Hospital — Dublin

Испания · 1 центр

• Sant Pau Biomedical Research Institute (IIB Sant Pau) — Barcelona

Великобритания · 1 центр

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

Публикации

• 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
• 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
• 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
• 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
• 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. PMID 26079411
• 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 PMID 28946567
• 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
• 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

Идентификаторы

NCT: NCT04165109 · ATRI-006 · 1R61AG066543-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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