Cholinergic Integrity in Down Syndrome in Association With Aging, Alzheimer's Disease Pathology, … (NCT05231798) | Clinical Trial Compass
RecruitingPhase 2
Cholinergic Integrity in Down Syndrome in Association With Aging, Alzheimer's Disease Pathology, and Cognition
United States30 participantsStarted 2021-08-19
Plain-language summary
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.
Who can participate
Age range
18 Years – 55 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Diagnosis of Down syndrome (DS), including mosaic DS or partial trisomy 21.
. Provision of signed and dated informed consent form and if needed, assent with signed consent by a legally authorized representative (LAR).
. Stated willingness to comply with all study procedures and availability for the duration of the study
. Male or female, aged 18-55 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, the medical monitoring team will review on case-by-case basis to recommend timing of baseline cognitive testing
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1This trial is using a radioactive tracer called [18F]-FEOBV in a PET scan to measure cholinergic system activity in the brain — can you explain what that scan involves for someone with Down syndrome, and whether the radiation exposure or the scan process itself carries any particular risks we should think about?
2Since this is a Phase 2 study focused on understanding how the cholinergic system in the brain relates to Alzheimer's disease changes in people with Down syndrome, does this trial offer any direct treatment, or is it purely observational — and what would we gain from participating versus not?
3The trial is looking at how brain chemistry connects to aging and Alzheimer's pathology specifically in Down syndrome — given where my family member is right now in terms of age and cognitive status, is this the right time to consider enrolling, or would their stage of progression affect whether they'd be a good fit for what the researchers are trying to measure?
4Because this study is measuring cholinergic integrity alongside Alzheimer's disease pathology, will participants receive any information about their own results, such as whether Alzheimer's-related changes are already present in their brain, and how should we prepare emotionally or practically for that kind of disclosure?
5Are there any logistical demands of this trial — like how many visits are required, whether travel to a specialized imaging center is needed, or how long each PET scan session takes — that we should weigh against the potential benefits of participating?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
[18F]-FEOBV radiotracer standardized uptake value ratio correlation with the Basal Forebrain Cholinergic System Volume.
Timeframe: Analysis will be completed at study completion in approximately 3 years.
. Adequate visual and auditory acuity to allow neuropsychological testing
. For females who are not surgically sterile or post-menopausal by two years: negative pregnancy test 24 hours prior to PET scan.
Exclusion criteria
. 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)
. 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 and PET procedures
. IQ less than 40 (as assessed by Kaufman Brief Intelligence Test, Second Edition (KBIT-2).
. Pregnancy, breast-feeding
. 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