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

NCT05231798 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 210933
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Down Syndrome; Down Syndrome, Partial Trisomy 21; Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• [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.

  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

  Analysis will be completed at study completion in approximately 3 years.

Study Arms (1)

Down Syndrome

EXPERIMENTAL

Adults between 18-55 with Down Syndrome.

Drug: [18F]-FEOBV Radiotracer

Interventions

[18F]-FEOBV Radiotracer DRUG

Participants will be administered an \[18F\]-fluoroethoxybenzovesamicol (FEOBV) radiotracer for diagnostic imaging purposes (PET scan).

Also known as: [18F]-fluoroethoxybenzovesamicol

Down Syndrome

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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 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

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• Vanderbilt Kennedy Center: collaborator

Study Sites (1)

Vanderbilt University Medical Center Clinical Research Center

Nashville, Tennessee, 37212, United States

Location

MeSH Terms

Conditions

Down Syndrome; Alzheimer Disease

Interventions

fluoroethoxy-benzovesamicol

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Dementia; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Alexander C Conley, Ph.D.

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

• Paul A Newhouse, M.D.

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD, Principal Investigator

Study Record Dates

• First Submitted: January 17, 2022
• First Posted: February 9, 2022
• Study Start: August 19, 2021
• Primary Completion: December 30, 2025
• Study Completion: April 30, 2026
• Last Updated: June 27, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• 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.

Locations

US (1)