A Phase 2 interventional study of [18F]-FEOBV Radiotracer in Down Syndrome, Down Syndrome, Partial Trisomy 21 and Alzheimer Disease, sponsored by Vanderbilt University Medical Center. Recruiting at 1 site in United States. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-06-22.
Sponsored by Vanderbilt University Medical Center · Phase 2, Interventional, and Other
Progressive age-related cognitive deficits occurring in both AD and DS have been connected to the degeneration of several neuronal populations, but mechanisms are not fully elucidated. The most consistent neuronal losses throughout the progression of AD are seen in cholinergic neurons where these losses negatively affect cognition, particularly in attention, learning, and memory formation. Evidence of reduced cholinergic integrity in DS is largely limited to animal models and post-mortem human data. The investigators propose to use molecular, functional, and structural biomarkers to assess the cholinergic integrity in adults with DS. The investigators anticipate using the data gathered in this pilot study to inform future study designs to determine AD risk stratification in DS by identifying individuals who show an accelerated decline in cholinergic integrity that correlates with cognitive and neurobehavioral changes. Also, our cholinergic biomarkers may identify whether individuals with DS are likely to respond to pro-cholinergic interventions, including the novel cholinergic modulators that are being developed to enhance cholinergic-sensitive cognitive functioning. The investigators anticipate using the data gathered here to inform future treatment studies in TRC-DS and beyond where novel cholinergic treatments may offer opportunities for early intervention in DS and be complementary to disease-modifying approaches such as anti-amyloid treatments.
Down syndrome (DS) or Trisomy 21, is the most common genetic cause of intellectual disability. Among its consequences, by the age of 30, people with DS invariably develop amyloid plaques and neurofibrillary tangles such that up to 75% of people with DS will develop Alzheimer's disease (AD). AD in DS is thought to be linked to the presence of three copies of the amyloid precursor protein (APP) gene, which resides on chromosome 21. This gene leads to higher levels of amyloid-β (Aβ) plaques. Preliminary data show that adults with DS exhibit significant changes in AD-related biomarkers between the ages of 35-55. It is also within this age range that AD-related cognitive decline and dementia typically manifest in DS. AD is the primary cause of death in adults with DS over the age of 35. Although it is currently suggested that the onset of dementia in DS is in part due to triplication of the amyloid precursor protein (APP) gene, other neurodegenerative features of sporadic AD may occur in DS and these can aggravate the onset of cognitive decline and dementia. Progressive cognitive deficits occurring in sporadic AD are associated with the degeneration of several neuronal populations. Throughout the progression of AD, the most consistent losses are seen in cholinergic neurons. While the loss of the cholinergic integrity has been established as a critical biological process in sporadic AD, the cholinergic system has not been evaluated in adults with DS to examine if age-related cholinergic decline can be detected in DS and whether it is associated with the progression of AD pathologies and cognitive decline as seen in sporadic AD.
The investigators propose to conduct a pilot study that aims to assess the integrity of the cholinergic neurotransmission system using in-vivo structural, functional, and molecular imaging biomarkers.
The examination of the cholinergic system in DS and its relationship to aging and known AD pathologies and cognitive decline would help validate whether the cholinergic decline is an early marker of dementia risk in DS and proceeds or follows changes in standard AD imaging and fluid biomarkers, thus helping establish how similar AD in DS is to that of sporadic AD. The investigators anticipate using the data gathered here to inform future treatment studies where novel cholinergic treatments may offer opportunities for early intervention in DS and be complementary to disease-modifying approaches such as anti-amyloid treatments.
Objective: To examine the molecular, functional, and structural biomarkers of cholinergic integrity in Down syndrome (DS) in association with age, Alzheimer's disease (AD) pathology, and cognitive/neurobehavioral performance.
Specific Aim: The Center for Cognitive Medicine is a site for the Trial-Ready Cohort-Down Syndrome (TRC-DS) study, to enable a systematic biomarker characterization of middle-aged and older individuals with DS by using neuroimaging, cognitive, and clinical measures, in preparation for an AD-like prevention trial likely using anti-amyloid agents. The investigators will leverage this cohort's well-characterized DS participants to initiate a new pathway for investigating our novel cholinergic biomarker in 10 TRC-DS participants (age:35-55) and enroll 110 additional adults with DS (age:18-55) outside of the TRC-DS study.
The investigators will use molecular, functional, and structural biomarkers to measure the cholinergic integrity of adults with DS. These methods will include resting and task-related electroencephalogram (EEG), basal forebrain volumetric measures on structural magnetic resonance imaging (MRI), and positron emission tomography (PET) with a vesicular cholinergic radiotracer known as fluoroethoxybenzovesamicol ([18F]FEOBV).
438 studies on the registry are indexed under Down Syndrome; 99 are open to participants now.
This study's planned enrollment of 30 is below the median of 37 across 286 interventional studies indexed under Down Syndrome.
Browse Down Syndrome studies →Vanderbilt University Medical Center is the lead sponsor of 833 studies on the registry; 155 are open to participants now.
Of its 125 completed or terminated interventional studies of FDA-regulated products, 92 (74%) have results posted.
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Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
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Postmenopausal
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INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
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Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
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Adults between 18-55 with Down Syndrome.
Drug: [18F]-FEOBV Radiotracer
Participants will be administered an \[18F\]-fluoroethoxybenzovesamicol (FEOBV) radiotracer for diagnostic imaging purposes (PET scan).
Also known as: [18F]-fluoroethoxybenzovesamicol
[18F]-FEOBV radiotracer standardized uptake value ratio correlation with the Basal Forebrain Cholinergic System Volume.
The association of \[18F\]-FEOBV radiotracer standardized uptake value ratio with the the gray matter volume of the cholinergic basal forebrain in adults with Down syndrome.
Time frame: Analysis will be completed at study completion in approximately 3 years.
EEG resting state power correlation with [18F]-FEOBV radiotracer standardized uptake value ratio
The association of EEG resting state power with \[18F\]-FEOBV radiotracer standardized uptake value ratio in adults with Down syndrome.
Time frame: Analysis will be completed at study completion in approximately 3 years.
Plan to share: Yes — De-identified participant data will be available upon request.
Supporting information: Study protocol, Statistical analysis plan, Clinical study report
Time frame: Data will become available after the study completion, anticipated to be 08/19/2024
Access criteria: Access will be granted to qualified individuals upon request.
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