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

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ClinicalTrials.gov Identifier: NCT04165109
Recruitment Status : Not yet recruiting
First Posted : November 15, 2019
Last Update Posted : July 20, 2020
Sponsor:
Collaborators:
National Institute on Aging (NIA)
Alzheimer's Clinical Trial Consortium
Alzheimer's Therapeutic Research Institute
Information provided by (Responsible Party):
Michael Rafii, MD, PhD, University of Southern California

Brief Summary:
The purpose of the Trial-Ready Cohort - Down Syndrome (TRC-DS) is to enroll 120 non-demented adults (ages 35-55) with Down syndrome (DS) into a trial ready cohort (TRC). 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.

Condition or disease
Down Syndrome Alzheimer Disease Dementia

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Study Type : Observational
Estimated Enrollment : 120 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Alzheimer's Clinical Trial Consortium for Down Syndrome (ACTC-DS) Trial-Ready Cohort - Down Syndrome (TRC-DS)
Estimated Study Start Date : September 2020
Estimated Primary Completion Date : December 2025
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Down Syndrome

Group/Cohort
Trial Ready Cohort
Non-demented adults with Down syndrome (DS)



Primary Outcome Measures :
  1. Enrollment of 120 participants into the Trial-Ready Cohort in DS (TRC-DS). [ Time Frame: 5 years ]
    The primary aim of the TRC-DS is enrollment of 120 participants into the trial ready cohort to support future referral and enrollment into primary Alzheimer's disease (AD) prevention trials for adults with DS.


Secondary Outcome Measures :
  1. Change in cognition as measured by the Cued Recall Test [ Time Frame: Baseline and every 16 months through end of study or enrollment into a clinical trial, up to 5 years ]
    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.

  2. Change in behavior as measured by the Neuropsychiatric Inventory- Questionnaire (NPI-Q) [ Time Frame: Baseline and every 16 months through end of study or enrollment into a clinical trial, up to 5 years ]
    The NPI-Q is a 12-item questionnaire that assesses behaviors in dementia patients and has been used in Down syndrome.

  3. Change in cognition as measured by the Down Syndrome Mental Status Exam (DSMSE) [ Time Frame: Screening and every 16 months through end of study or enrollment into a clinical trial, up to 5 years ]
    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.

  4. Change in behavior as measured by the Vineland 3 [ Time Frame: Baseline and every 16 months through end of study or enrollment into a clinical trial, up to 5 years ]
    The Vineland 3 is a normed assessment tool that assesses adaptive behavior across the areas of communication, activities of daily living, and socialization. The tool is administered via interview to a caregiver and takes approximately 45 minutes to complete.

  5. Change in cognition as measured by the National Task Group Early Detection Screen for Dementia (NTG-EDSD) [ Time Frame: Baseline, every 8 months (over the phone) and every 16 months (in person) through end of study or enrollment into a clinical trial, up to 5 years ]
    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.

  6. Change in cognition as measured by the Stroop Dog and Cat Task [ Time Frame: Baseline and every 16 months through end of study or enrollment into a clinical trial, up to 5 years ]
    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.

  7. Change in verbal learning and cognition as measured by the modified Selective Reminding Test (SRT) [ Time Frame: Baseline and every 16 months through end of study or enrollment into a clinical trial, up to 5 years ]
    The modified SRT is a test designed to measure verbal learning and memory through the use of a list-learning procedure over multiple trials. This paradigm is believed to separate verbal memory into distinct processes. The modified SRT involves reading the participant a list of 12 unrelated words and then having the participant immediately recall as many of these 12 words as possible. Every trial after the first involves selectively presenting only those words in which the participant did not recall on the immediately preceding trial. The selective reminding trials proceed in this manner until the participant is able to correctly recall all 12 words on three consecutive trials.

  8. Change in cognition as measured by the Brief Praxis Test (BPT) [ Time Frame: Baseline and every 16 months through end of study or enrollment into a clinical trial, up to 5 years ]
    The Brief Praxis Test (BPT), evaluates simple sequences of voluntary movements expected to deteriorate with the onset and progression of dementia in AD among persons at all levels of premorbid intellectual disability. Participants are given points for each task they are able to perform.

  9. Change in amyloid deposition as measured by SUVR on Positron Imaging Tomography (PET) scan [ Time Frame: Baseline and every 16 months through end of study or enrollment into a clinical trial, up to 5 years ]
  10. Change in brain volume as measured by magnetic resonance imaging (MRI) [ Time Frame: Baseline and every 16 months through end of study or enrollment into a clinical trial, up to 5 years ]
  11. Change in plasma Amyloid Beta (Abeta) biomarkers [ Time Frame: Baseline and every 16 months through end of study or enrollment into a clinical trial, up to 5 years ]
  12. Change in plasma tau biomarkers [ Time Frame: Baseline and every 16 months through end of study or enrollment into a clinical trial, up to 5 years ]

Biospecimen Retention:   Samples With DNA
Blood, Urine, CSF


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   35 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
120 non-demented adults with Down Syndrome
Criteria

Inclusion Criteria:

  1. Diagnosis of DS (including mosaic DS or partial trisomy 21) who are capable of providing consent to participate, or for whom a legally authorized representative (LAR) may give permission on behalf of the individual to participate. Adults with DS who cannot consent for themselves but can provide assent would need to provide assent
  2. Provision of signed and dated informed consent form and if needed, assent with signed 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 (i.e. 2 years) or until referred to a clinical trial
  4. Male or female, aged 35-55 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)
  9. IQ less 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 neuropsychological testing (i.e., 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 and PET procedures
  4. For females who are not surgically sterile or post-menopausal by two years: Positive Pregnancy test 48 hours prior to amyloid PET scan, or currently breast-feeding
  5. 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
  6. 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
  7. Clinically significant abnormalities in screening ECG or laboratories
  8. Answer "Yes" to C-SSRS suicidal ideation Type 4 or 5 or behavior
  9. 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)
  10. Concurrent participation in a clinical trial for an investigational product or concurrent participation in longitudinal study with overlapping outcome measures/procedures is prohibited
  11. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04165109


Contacts
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Contact: ATRI Recruitment Team 858-964-0638 atri-recruit@usc.edu

Sponsors and Collaborators
University of Southern California
National Institute on Aging (NIA)
Alzheimer's Clinical Trial Consortium
Alzheimer's Therapeutic Research Institute
Investigators
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Principal Investigator: Michael Rafii, MD, PhD USC Alzheimer's Therapeutic Research Institute (ATRI)
Additional Information:
Publications:

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Responsible Party: Michael Rafii, MD, PhD, Professor, University of Southern California
ClinicalTrials.gov Identifier: NCT04165109    
Other Study ID Numbers: ATRI-006
1R61AG066543-01 ( U.S. NIH Grant/Contract )
First Posted: November 15, 2019    Key Record Dates
Last Update Posted: July 20, 2020
Last Verified: July 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Michael Rafii, MD, PhD, University of Southern California:
Trial-Ready Cohort
Observational
Alzheimer's
Prevention
Down Syndrome
Additional relevant MeSH terms:
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Alzheimer Disease
Down Syndrome
Syndrome
Disease
Pathologic Processes
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn