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

Study Overview
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Brief Summary
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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 250 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/.

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

Conditions
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Down Syndrome, Alzheimer Disease, Dementia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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 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

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Trial Ready Cohort<br>Non-demented adults with Down syndrome (DS) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 250 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cognition as measured by the Cued Recall Test | The Cued Recall Test is modified from a version developed for adults from the typical population. Twelve items are presented for learning, 4 at a time, with each item accompanied by a unique category cue. The testing phase consists of 3 trials. Each trial begins with free recall of the test items; following free recall, a category cue is provided for those items not spontaneously recalled. Two scores are generated from the test, a Free Recall Score and a Total Score (Free Recall plus items recalled when the category cue is provided). A cut-off of < 23 on the Total Score resulted in a sensitivity of 91% and a specificity of 84% when individuals with DS and a diagnosis of dementia were compared to their healthy peers without dementia. | Baseline and Month 32, or until enrollment into a clinical trial | 
| Change in behavior as measured by the Neuropsychiatric Inventory (NPI) | The Neuropsychiatric Inventory (NPI) is a well-validated, reliable, multi-item instrument to assess psychopathology in AD based on an interview with a caregiver or qualified study partner. It evaluates both the frequency and severity of 12 neuropsychiatric features including delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, aberrant motor behavior, sleep, and appetite and eating disorders. A higher NPI score means that the participant is displaying more behavioral symptoms. The minimum score is 0 and the maximum is 144. A score of 0-20 is mild, 20-50 moderate and greater than 50 means significant behavioral symptoms. | Screening and Month 32, or until enrollment into a clinical trial | 
| Change in cognition as measured by the Down Syndrome Mental Status Exam (DSMSE) | The DSMSE is an omnibus measure of neuropsychological function that assesses a broad range of skills and is easy to administer. It is divided into items that test recall for personal information, orientation to season and day of week, memory, language, visuospatial function, and praxis. Recall for personal information is tested with questions about the subject's name, age and birth date. Orientation items ask the day of the week and season of the year. Memory in the DSMSE is assessed with items that require immediate and delayed recall of three objects and for the location of three hidden objects. Language items include confrontation naming, sentence repetition, and comprehension of one, two, and three step commands. Visuospatial items are three-dimensional block constructions. Praxis items include transitive and intransitive limb movements and a sequential task. | Screening and Month 32, or until enrollment into a clinical trial | 
| Change in behavior as measured by the Vineland 3 (Informant Version) | The Vineland Adaptive Behavior Scale 3 (VABS-II) I is a normed assessment tool that assesses adaptive behavior across the areas of communication, activities of daily living, and socialization. The tool is self-administered via interview toby a study partner using a tablet (e.g. iPad), takes approximately 45 minutes to complete and may be done remotely. The VABS-III scores range from 20-140. Higher scores indicate higher functioning. Specifically, these include 'very high' (domain and Adaptive Behavior Scale (ABC) Standard Scores of 130-140), moderately high (domain and ABC Standard Scores of 115-129), adequate (domain and ABC Standard Scores of 86-114), moderately low (domain and ABC Standard Scores of 71-85), and low (domain and ABC Standard Scores of 20-70). | 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) | The National Task Group Early Detection Screen for Dementia (NTG-EDSD) is a screening tool which measures changes typically observed in dementia. It is composed of four primary sections about relative demographics, ratings of health, mental health, and life stressors, a review of multiple domains associated with adult functioning, and a review of chronic medical conditions. The NTG-EDSD is completed by a staff member who interviews the caregiver. It contains 40 questions/question groups and takes 15 mins to administer. | Baseline and Month 32, or until enrollment into a clinical trial | 
| Change in cognition as measured by the Stroop Dog and Cat Task | In the Stroop Dog and Cat Task, a linear sequence of 16 pictures (8 cats, 8 dogs) are presented in a pre-determined random order. In the control condition the subject says the name of each picture and is urged to do so rapidly. In the experimental (inhibition) condition the participant is required to say 'cat' for the picture of each dog and 'dog' for the cat. For each condition the participant is given a brief practice period. Performance on the Stroop Dog and Cat was significantly related to informant-reported memory changes in 103 adults with DS with mild-moderate intellectual disability in the age range of 36 - 72 years. | Baseline and Month 32, or until enrollment into a clinical trial | 
| Change in brain volume as measured by magnetic resonance imaging (MRI) |  | Baseline and Month 32, or until enrollment into a clinical trial | 
| Change in plasma Amyloid Beta (Abeta) biomarkers |  | Baseline and Month 32, or until enrollment into a clinical trial | 
| Change in plasma tau biomarkers |  | Baseline and Month 32, or until enrollment into a clinical trial | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Trial-Ready Cohort, Observational, Alzheimer's, Prevention, Down Syndrome