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

Purpose

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.

Conditions

  • Down Syndrome
  • Alzheimer Disease
  • Dementia

Eligibility

Eligible Ages
Between 35 Years and 55 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Study Type
Observational
Observational Model
Cohort
Time Perspective
Prospective

Arm Groups

ArmDescriptionAssigned Intervention
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 names:
    • [18F]MK-6240

Recruiting Locations

Vanderbilt University Medical Center Center for Cognitive Medicine
Nashville, Tennessee 37212
Contact:
Amy Boegel, Dr.
615-875-0955
amy.r.boegel@vumc.org

More Details

Status
Recruiting
Sponsor
University of Southern California

Study Contact

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