Elucidating the Role of Cholinergic Degeneration in Cognitive Fluctuations in Lewy Body Dementia

Part of paid clinical trials in Richmond, Virginia.

Sponsor
Virginia Commonwealth University
Study ID
NCT07284290
Phase
PHASE4
Status
Recruiting
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Conditions

  • Dementia With Lewy Bodies
  • Healthy Controls
  • Parkinson Disease Dementia

Eligibility Criteria

Sex
ALL
Age
50 Years - 89 Years
Healthy Volunteers
Accepted

Interventions

  • Syn-One skin biopsy — PROCEDURE
    Detects phosphorylated alpha synuclein in cutaneous nerve fibrils which has \>95% sensitivity in detecting DLB
  • Multi modal MRI — DIAGNOSTIC_TEST
    Functional MRI used to investigate the network connectivity changes associated with alterations in the cholinergic system. Using this comprehensive methodology to establish cholinergic degeneration's contribution to CF provides a robust framework for future research and therapeutic strategies.
  • Assessment of dynamic EEG features over 48-hour periods across all study aims — DIAGNOSTIC_TEST
    Implementing prolonged EEG monitoring, to capture dynamic changes in neural activity associated with CF. The methods are designed avoid the limitations identified in a systematic review of EEG studies in DLB, as will use quantitative analysis of EEG, uniformly apply diagnostic criteria, and consider the confounding effects of medications. Concurrent evaluation of PVT performance and EEG This dual assessment will correlate cognitive and neurophysiological dynamics in real-time, providing a more holistic understanding of CF over time and the functional brain activity that underlies them. Temporal integration of PVT with EEG data collection will enable the identity of specific correlates of CF.
  • Plasma biomarkers — DIAGNOSTIC_TEST
    A blood sample will be collected and sent for processing by C2N Diagnostics for the detection of Aβ42/40 and p-tau217 via mass spectrometry, a method shown to be highly accurate for predicting amyloid positivity on PET (AUC=0.94). Exploratory Biomarkers: The additional blood sample will be used for analysis of exploratory biomarkers and future research. A total of up to 20mL of blood will be taken.
  • Galantamine HBr extended-release 8mg capsules (8mg ER). — DRUG
    20 participants from the arm 1. Participants will take 1 capsule daily of galantamine 8mg ER for 4 weeks and then increase to 2 capsules daily of galantamine 8mg ER (16mg) for 4 weeks. This titration will mitigate potential for cholinergic side effects. At 2 weeks, 4 weeks and 6 weeks of the treatment period, safety and compliance will be assessed during phone call visits. Any adverse event rated as Grade 2 or greater according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and that is definitely or possibly attributable to the study drug will result in study drug withdrawal or dose reduction.

Study Details

The proposed study aims to address the critical gaps in understanding the mechanisms of CF (Cognitive Fluctuations) by leveraging recently emerged molecular biomarkers, advanced neuroimaging techniques to assess measures of cholinergic degeneration, and synchronous EEG and assessments of attention. One of the overarching innovations of study is combining all of these assessments into one integrated research plan

Key Dates

Start date
Dec 8, 2025
Status verified
Mar 2026
Primary completion
Nov 30, 2029
Completion
Nov 30, 2029

Study Design

Enrollment
120 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE

Arms

  • Experimental: Subjects with DLB or PDD
    90 subjects with Dementia with Lewy Bodies (DLB) or Parkinson's Disease with Dementia (PDD)
  • Active Comparator: Subjects with Lewy Body disease with CF
    A subset of 20 subjects with Lewy Body (LB) disease with Cognitive fluctuations (CF) This arm will be a subset of 20 subjects from Arm #1 (Subjects with DLB or PDD).
  • Other: Healthy control subjects
    30 healthy controls

Primary Outcome Measure

Clinical Assessment of Fluctuations (CAF) (frequency and duration score) [ Time Frame: Screening, Baseline, ChEI Cohort Day 56, 1 year follow-up visit, and 2 year follow-up visit ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
Virginia Commonwealth UniversityRichmondVirginia23298
Kara McHaney
[email protected]
(804) 828-4788
Matthew Barrett, MD (PRINCIPAL_INVESTIGATOR)

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By research site
Virginia Commonwealth University· Richmond, VA

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