Down SyndromePhase 2NCT05231798
Cholinergic Integrity in Down Syndrome in Association With Aging, Alzheimer's Disease Pathology, and Cognition
A Phase 2 study testing [18F]-FEOBV Radiotracer in people with Down Syndrome and Down Syndrome, Partial Trisomy 21, run by Vanderbilt University Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Down Syndrome, Down Syndrome, Partial Trisomy 21, Alzheimer Disease
- What is being tested?
- [18F]-FEOBV Radiotracer
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Aug 2021to 30 Apr 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Show all 11Show fewer
- 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.
- Mental Age of 4 years or greater (based upon the Kaufman Brief Intelligence Test, 2nd Edition)
- English must be first/native language
- Reliable Study Partner (may be caregiver, sibling, parent) who can provide information about the subject's clinical symptoms and history
Who cannot join
- 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
Show all 12Show fewer
- 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
- 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)
- Participants whom the Site PI deems to be otherwise ineligible
- Clinical diagnosis of dementia
- Concurrent participation in a clinical trial for an investigational product or concurrent participation in a longitudinal study with overlapping outcome measures/procedures is prohibited
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Vanderbilt University Medical Center Clinical Research Center
Nashville, Tennessee, 37212
Amy Boegel, 615-875-0955, amy.r.boegel@vumc.org
About this study
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.
Read the detailed description
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).
- Being tested
- [18F]-FEOBV Radiotracer
- Medical subject headings
- Down Syndrome, Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[18F]-FEOBV RadiotracerDrug
Also called [18F]-fluoroethoxybenzovesamicol
Participants will be administered an [18F]-fluoroethoxybenzovesamicol (FEOBV) radiotracer for diagnostic imaging purposes (PET scan).
| Study group | Role | What they receive |
|---|---|---|
| Down Syndrome | Experimental | Adults between 18-55 with Down Syndrome. Receives: Drug: [18F]-FEOBV Radiotracer |
What is being measured
The primary outcome is the main question the study is designed to answer.
[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.
Measured: Analysis will be completed at study completion in approximately 3 years.
Secondary outcomes (1)
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.
Measured: Analysis will be completed at study completion in approximately 3 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2022
- Study start19 Aug 2021
- Primary completion30 Apr 2027 (estimated)
- Study completion30 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Down SyndromeStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Vanderbilt Kennedy Center, Alzheimer's Association, Fondation Jérôme Lejeune, National Institute on Aging (NIA)
- Responsible party
- Principal investigator, Paul Newhouse, Vanderbilt University Medical Center
- Investigators
- Alexander C Conley, Ph.D., Principal investigator, Vanderbilt University Medical CenterPaul A Newhouse, M.D., Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05231798
- Sponsor's protocol ID
- 210933
- Status last verified
- Jun 2026
- First submitted
- 17 Jan 2022
- Last updated
- 22 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified participant data will be available upon request.
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cholinergic Integrity in Down Syndrome in Association With Aging, Alzheimer's Disease Pathology, and Cognition
- ClinicalTrials.gov ID
- NCT05231798
- Acronym / sponsor ID
- 210933
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Collaborators
- Vanderbilt Kennedy Center, Alzheimer's Association, Fondation Jérôme Lejeune, National Institute on Aging (NIA)
- Study start
- 19 Aug 2021 (actual)
- Primary completion
- 30 Apr 2027 (estimated)
- Study completion
- 30 Apr 2027 (estimated)
- First posted
- 9 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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).
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Down Syndrome | Experimental | Drug: [18F]-FEOBV RadiotracerAdults between 18-55 with Down Syndrome. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [18F]-FEOBV RadiotracerAlso: [18F]-fluoroethoxybenzovesamicolParticipants will be administered an [18F]-fluoroethoxybenzovesamicol (FEOBV) radiotracer for diagnostic imaging purposes (PET scan). | Drug | Down Syndrome |
Primary outcome
[18F]-FEOBV radiotracer standardized uptake value ratio correlation with the Basal Forebrain Cholinergic System Volume.
Time frame: Analysis will be completed at study completion in approximately 3 years.
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.
1 secondary outcome
EEG resting state power correlation with [18F]-FEOBV radiotracer standardized uptake value ratio
Time frame: Analysis will be completed at study completion in approximately 3 years.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2026.
- Individual participant dataSharing planned: Yes. De-identified participant data will be available upon request.
Related trials for Down Syndrome
Not yet recruitingPhase 4
Oral Switch in Bloodstream Infections in Immunocompromised Children
Bloodstream Infection, Bloodstream Infection Due to Central Venous Catheter
Not yet recruiting
Fecal Microbiota Transplantation (FMT) to Slow Biological Aging
Aging, Healthy, Aging and Cognitive Health
Active, not recruitingPhase 3
A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia
B Acute Lymphoblastic Leukemia, B Lymphoblastic Lymphoma
Not yet recruiting
Executive Function Play Opportunities for Children With Down Syndrome
Down Syndrome, Trisomy 21
RecruitingObservational study
Natural History of Dysregulation and Aging of the Immune System in People With Trisomy 21 With and Without Thymectomy
Down Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Alexander C Conley, Ph.D. principal investigator
Vanderbilt University Medical Center
Paul A Newhouse, M.D. principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing [18F]-FEOBV Radiotracer in people with Down Syndrome and Down Syndrome, Partial Trisomy 21, run by Vanderbilt University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kiara Baker (615-327-7117, Kiara.Baker@vumc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
[18F]-FEOBV radiotracer standardized uptake value ratio correlation with the Basal Forebrain Cholinergic System Volume. (time frame: Analysis will be completed at study completion in approximately 3 years.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2026.