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RecruitingPhase 2

Cholinergic Integrity in Down Syndrome in Association With Aging, Alzheimer's Disease Pathology, and Cognition

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years to 55 Years
Sex
All sexes
Healthy volunteers
Accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Procedures mentioned: MRI scans

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "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)."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study looks at brain nerve cells that help with attention, learning, and memory in adults with Down syndrome ages 18–55 who do not have dementia. Researchers will use brain scans and tests to learn how these cells relate to aging, signs of Alzheimer's disease, and thinking skills.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Have Down syndrome, including mosaic Down syndrome or partial trisomy 21, and be age 18–55.
  • Sign a consent form, with agreement and signed consent from a legal representative if needed. Be willing and available to complete the study.
  • Be in good general health and have no dementia diagnosis.
  • Take only allowed medicines that affect the brain, with doses unchanged for at least 4 weeks or longer. The study team will review any new medicines.
  • Have enough sight and hearing to complete thinking tests. English must be your first language.
  • Have thinking skills at the level of a child age 4 or older, based on a study test.
  • Have a reliable study partner, such as a caregiver or family member, who can share information about your symptoms and health history.
  • Women must have a negative pregnancy test within 24 hours before the PET brain scan, unless surgery prevents pregnancy or menopause was at least 2 years ago.

Who can't join

  • Have dementia, an IQ below 40 on the study test, or a serious or unstable illness that could affect thinking tests.
  • Cannot safely have an MRI scan, such as because of a pacemaker, certain metal pieces, or a hearing implant; or cannot complete MRI and PET scans. Dental fillings are allowed.
  • Are pregnant or breastfeeding.
  • Have had new or returning cancer within the past 5 years. Some skin cancers and certain very early cancers of the cervix or prostate are allowed.
  • Have important abnormal screening blood tests, including vitamin B12 or thyroid results. Some B12 or thyroid results may be allowed after follow-up tests.
  • If having spinal fluid collected: have a bleeding or blood-clotting disorder, abnormal clotting tests, or take blood thinners such as warfarin.
  • Are also in a trial of an experimental product, or a long-term study with overlapping tests or procedures.
  • The lead study doctor decides you are not eligible for another reason.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

Inclusion Criteria: 1. Diagnosis of Down syndrome (DS), including mosaic DS or partial trisomy 21. 2. Provision of signed and dated informed consent form and if needed, assent with signed consent by a legally authorized representative (LAR). 3. Stated willingness to comply with all study procedures and availability for the duration of the study 4. Male or female, aged 18-55 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, the 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. For females who are not surgically sterile or post-menopausal by two years: negative pregnancy test 24 hours prior to PET scan. 9. Mental Age of 4 years or greater (based upon the Kaufman Brief Intelligence Test, 2nd Edition) 10. English must be first/native language 11. Reliable Study Partner (may be caregiver, sibling, parent) who can provide information about the subject'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. IQ less than 40 (as assessed by Kaufman Brief Intelligence Test, Second Edition (KBIT-2). 5. Pregnancy, breast-feeding 6. 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 7. 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. 8. Clinically significant abnormalities in screening laboratories 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 (e.g warfarin) 10. Participants whom the Site PI deems to be otherwise ineligible 11. Clinical diagnosis of dementia 12. Concurrent participation in a clinical trial for an investigational product or concurrent participation in a longitudinal study with overlapping outcome measures/procedures is prohibited

Study sites (1)

TN