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

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ClinicalTrials.gov Identifier: NCT04165109
Recruitment Status : Recruiting
First Posted : November 15, 2019
Last Update Posted : September 5, 2021
Sponsor:
Collaborators:
National Institute on Aging (NIA)
Alzheimer's Clinical Trials 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 Intervention/treatment
Down Syndrome Alzheimer Disease Dementia Radiation: Flutafuranol Radiation: Pittsburgh Compound (PIB) Radiation: MK6240

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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)
Actual Study Start Date : June 7, 2021
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 Intervention/treatment
Trial Ready Cohort
Non-demented adults with Down syndrome (DS)
Radiation: Flutafuranol
All participants at qualifying sites will receive a single bolus intravenous injection of 8.1 mCi (300 MBq) (+/- 20%, 10μg mass dose) of flutafuranol ([18F]NAV4694). At approximately 90-minutes post dose, scanning will begin. An approximately 30-minute image acquisition scan will be performed.
Other Names:
  • [18F]NAV4694
  • NAV4694

Radiation: Pittsburgh Compound (PIB)
All participants at qualifying sites will receive a single bolus intravenous injection of 15 mCi (555 MBq) (± 10%) of PIB. At approximately 30-minutes post dose, scanning will begin. An approximately 30-minute image acquisition scan will be performed.
Other Names:
  • [11C]-PIB
  • PIB

Radiation: MK6240
All participants at qualifying sites will receive a single bolus intravenous injection of 5 mCi (185 MBq) (± 20%) of MK6240. At approximately 90-minutes post dose, scanning will begin. An approximately 30-minute image acquisition scan will be performed.
Other Name: [18F]MK-6240




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 Month 16, or until enrollment into a clinical trial ]
    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 (NPI) [ Time Frame: Screening and Month 16, or until enrollment into a clinical trial ]
    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.

  3. Change in cognition as measured by the Down Syndrome Mental Status Exam (DSMSE) [ Time Frame: Screening and Month 16, or until enrollment into a clinical trial ]
    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 (Informant Version) [ Time Frame: Baseline and Month 16, or until enrollment into a clinical trial ]

    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).


  5. Change in cognition as measured by the National Task Group Early Detection Screen for Dementia (NTG-EDSD) [ Time Frame: Baseline and Month 16, or until enrollment into a clinical trial ]
    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 Month 16, or until enrollment into a clinical trial ]
    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 amyloid deposition as measured by SUVR on Positron Imaging Tomography (PET) scan [ Time Frame: Baseline and Month 16, or until enrollment into a clinical trial ]
  8. Change in brain volume as measured by magnetic resonance imaging (MRI) [ Time Frame: Baseline and Month 16, or until enrollment into a clinical trial ]
  9. Change in plasma Amyloid Beta (Abeta) biomarkers [ Time Frame: Baseline and Month 16, or until enrollment into a clinical trial ]
  10. Change in plasma tau biomarkers [ Time Frame: Baseline and Month 16, or until enrollment into a clinical trial ]

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 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 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 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 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 laboratories
  8. 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)
  9. 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
  10. 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

Locations
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United States, Arizona
Barrow Neurological Institute Not yet recruiting
Phoenix, Arizona, United States, 85013
United States, California
University of California, Irvine School of Medicine Not yet recruiting
Orange, California, United States, 92868
United States, Colorado
Linda Crnic Institute for Down Syndrome, University of Colorado Not yet recruiting
Aurora, Colorado, United States, 80045
United States, Indiana
Indiana University Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Katherine Britt    317-963-7427    brittk@iu.edu   
Principal Investigator: Jill Fodstad, PhD         
United States, Kentucky
University of Kentucky Not yet recruiting
Lexington, Kentucky, United States, 40504
United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
United States, Missouri
Washington University, St. Louis Not yet recruiting
Saint Louis, Missouri, United States, 63108
United States, New York
New York State Institute for Basic Research in Developmental Disabilities (SIBRDD) Not yet recruiting
Staten Island, New York, United States, 10314
United States, Ohio
Case Western Reserve University Not yet recruiting
Beachwood, Ohio, United States, 44122
United States, Pennsylvania
University of Pittsburgh Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
Vanderbilt University Medical Center Center for Cognitive Medicine Recruiting
Nashville, Tennessee, United States, 37212
Contact: Amy Boegel, Dr.    615-875-0955    amy.r.boegel@vumc.org   
Principal Investigator: Paul Newhouse, Dr.         
Spain
Sant Pau Biomedical Research Institute (IIB Sant Pau) Not yet recruiting
Barcelona, Spain, 08041
United Kingdom
University of Cambridge Not yet recruiting
Cambridge, United Kingdom, CB2 1TN
King's College London, Institute of Psychiatry, Psychology & Neuroscience Not yet recruiting
London, United Kingdom, SE5 8AF
Sponsors and Collaborators
University of Southern California
National Institute on Aging (NIA)
Alzheimer's Clinical Trials 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: September 5, 2021
Last Verified: September 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: 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