Recruiting

Cognitive Fluctuations

Sponsor:

Virginia Commonwealth University

Code:

NCT07284290

Conditions

Dementia With Lewy Bodies

Parkinson Disease Dementia

Healthy Controls

Eligibility Criteria

Sex: All

Age: 50 - 70+

Healthy Volunteers: Accepted

Interventions

Syn-One skin biopsy

Multi modal MRI

Assessment of dynamic EEG features over 48-hour periods across all study aims

Plasma biomarkers

Galantamine HBr extended-release 8mg capsules (8mg ER).

Study Details

Brief summary:

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

Conditions

Dementia With Lewy Bodies

Parkinson Disease Dementia

Healthy Controls

Study ID

NCT07284290

Start date

Dec 8, 2025

Status verified date

Mar, 2026

Completion date

Nov, 2029

Anticipated

Primary completion date

Nov, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 50 - 70+

Healthy Volunteers: Accepted

Inclusion Criteria:

Arm 1:

  • Age range: 50 ≤ age < 90.
  • Diagnosis of dementia with Lewy bodies (DLB), Parkinson disease dementia (PDD), Parkinson disease with Mild Cognitive Impairment (PD-MCI), Mild Cognitive Impairment with Lewy bodies (MCI-LB).
  • DLB participants must fulfill criteria for clinically probable DLB based on the 2017 4th consensus report of the DLB consortium.
  • PDD participants must meet criteria for clinically probable PD according to the MDS Clinical Diagnostic Criteria for Parkinson's Disease and must also meet criteria for probable PDD based on the 2007 Movement Disorders Society clinical diagnostic criteria.
  • PD-MCI participants must meet criteria for clinically probable PD according to the MDS Clinical Diagnostic Criteria for Parkinson's Disease and meet criteria for Mild Cognitive Impairment on cognitive testing at screening.
  • MCI-LB participants with must meet established research criteria.
  • Capacity to provide informed consent or, if unable, availability of a legally authorized representative or guardian who can provide informed consent.
  • Availability of informant (for participants meeting criteria for dementia).
  • Ability and willingness to comply with the study-related procedures.
  • Fluent in spoken and written English (due to cognitive testing)

Exclusion Criteria:

Arm 1

  • History of cognitive disorder or psychiatric disorder other than that related to dementia with Lewy bodies or Parkinson disease dementia.
  • History of deep brain stimulation or any neurosurgical procedure.
  • History of structural brain disease or known significant cerebrovascular disease.
  • History of seizures or epilepsy and/or use of sodium channel blockers, i.e. carbamazepine, oxcarbazepine, phenytoin, topiramate, lamotrigine, felbamate, zonisamide, rufinamide, lacosamide, eslicarbazepine, and valproate.
  • Greater than two alcoholic drinks per day for men and one per day for women.
  • Regular use of benzodiazepines or barbiturates. (If benzodiazepines are taken as needed only, these medications cannot be taken within 5 half-lives of screening visit or between screening visit and EEG.)
  • Severe dementia (based on PI assessment of subject dependence level for instrumental activities of daily living)
  • Any contraindication to brain MRI.
  • Any medical condition that would interfere with ability to complete all study procedures.
  • Participants must not be pregnant, planning to become pregnant, or father a child for the duration of the study

Inclusion Criteria:

Arm 2 (Cholinesterase inhibitor cohort) inclusion criteria:

  • Completed Aim 1.
  • Clinical diagnosis of LBD (DLB or PDD) with CF.
  • Not taking a cholinesterase inhibitor and has not taken a cholinesterase inhibitor in the previous 90 days.
  • Ability and willingness to comply with the ChEI Cohort procedures (including galantamine administration), or a caregiver willing and able to ensure compliance.

Exclusion Criteria:

Arm 2 (Cholinesterase inhibitor cohort) exclusion criteria:

  • Severe hepatic impairment.
  • Renal failure.
  • Significant bradycardia (<50 bpm) at screening or history of AV block.
  • Any contraindication to galantamine administration based on PI discretion.

Inclusion criteria:

Arm 3 (Healthy Controls)

  • Age range: 50 ≤ age < 90.
  • Healthy controls should not have any known neurologic conditions that could interfere with study procedures or results.
  • Capacity to provide informed consent or, if unable, availability of a legally authorized representative or guardian who can provide informed consent.
  • Availability of informant (for participants meeting criteria for dementia).
  • Ability and willingness to comply with the study-related procedures.
  • Fluent in spoken and written English (due to cognitive testing).

Exclusion Criteria:

Arm 3 (Healthy Controls)

  • No History of cognitive disorder or psychiatric disorder other than that related to dementia with Lewy bodies or Parkinson disease dementia.
  • No History of deep brain stimulation or any neurosurgical procedure.
  • No History of structural brain disease or known significant cerebrovascular disease.
  • No History of seizures or epilepsy and/or use of sodium channel blockers, i.e. carbamazepine, oxcarbazepine, phenytoin, topiramate, lamotrigine, felbamate, zonisamide, rufinamide, lacosamide, eslicarbazepine, and valproate.
  • Any medical condition that would interfere with ability to complete all study procedures.
  • Participants must not be pregnant, planning to become pregnant, or father a child for the duration of the study

Study Design

Enrollment

120 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Basic Science

Interventions and Outcome Measures

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

Interventions

Syn-One skin biopsy

Detects phosphorylated alpha synuclein in cutaneous nerve fibrils which has >95% sensitivity in detecting DLB

Multi modal MRI

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

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

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).

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.

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 ]
  • Dementia Cognitive Fluctuations Scale-Research Version (DCFS-R) (total score) [ Time Frame: Screening, Baseline, ChEI Cohort Day 56, 1 year follow-up visit, and 2 year follow-up visit ]
  • Mayo Fluctuations Scale (Four questions) [ Time Frame: Screening, Baseline, ChEI Cohort Day 56, 1 year follow-up visit, and 2 year follow-up visit ]
  • Functional Activities Questionnaire (FAQ Assessment) [ Time Frame: Screening, Baseline, 1 year follow-up visit, and 2 year follow-up visit ]
  • Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) [ Time Frame: Screening, Baseline, 1 year follow-up visit, and 2 year follow-up visit ]
  • REM Sleep Behavior Disorder Questionnaire (RBDSQ) [ Time Frame: Screening, Baseline, 1 year follow-up visit, and 2 year follow-up visit ]
  • Neuropsychiatric Inventory (NPI) [ Time Frame: Screening, Baseline, 1 year follow-up visit, and 2 year follow-up visit ]
  • Enhanced Scale for the assessment for Parkinson's Disease (SAPS-PD) [ Time Frame: Screening, Baseline, 1 year follow-up visit, and 2 year follow-up visit ]
  • Patient Health Questionnaire-9 (PHQ-9) [ Time Frame: Screening, Baseline, 1 year follow-up visit, and 2 year follow-up visit ]

Central Contacts and Locations

Central contacts

Kara McHaney

(804) 828-4788Kara.McHaney@vcuhealth.org

Locations

Virginia Commonwealth University

Recruiting

Richmond, Virginia, United States, 23298

Contacts

Kara McHaney

(804) 828-4788Kara.McHaney@vcuhealth.org

Principal Investigator:

Matthew Barrett, MD

More Information

Sponsor

Virginia Commonwealth University

Last update posted

Mar 6, 2026

Last verified

Mar, 2026

Keywords

  • Parkinson Disease with Mild Cognitive Impairment
  • Mild Cognitive Impairment with Lewy Bodies

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Virginia Commonwealth University on 2026-03-06.