Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| R01NS142622 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Institute of Neurological Disorders and Stroke (NINDS) | NIH |
Not provided
Not provided
Not provided
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
Aim 1 is a cross-sectional case control study in which cholinergic degeneration in 45 participants with DLB or PDD with CF will be compared to a group of 45 individuals with Lewy Body disease without CF and 30 healthy controls. The first 20 participants who are eligible for Aim 2 and consent will also participate in an 8-week pre-post interventional cohort study immediately following Aim 1 procedures. For Aim 3, Aim 1 participants will complete annual follow-up evaluations for 2 years to understand factors influencing the change in cognitive fluctuations over time.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Subjects with DLB or PDD | Experimental | 90 subjects with Dementia with Lewy Bodies (DLB) or Parkinson's Disease with Dementia (PDD) |
|
| Subjects with Lewy Body disease with CF | Active Comparator | 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). |
|
| Healthy control subjects | Other | 30 healthy controls |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Syn-One skin biopsy | Procedure | Detects phosphorylated alpha synuclein in cutaneous nerve fibrils which has >95% sensitivity in detecting DLB |
|
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Assessment of Fluctuations (CAF) (frequency and duration score) | The scoring for the Clinical Assessment of Fluctuations (CAF) is a two-step process that uses both a frequency and a duration score. The two scores are multiplied together to get the final severity rating. A higher score indicates more severe cognitive fluctuations. After rating the frequency and duration, the two scores are multiplied to get the final CAF score. Frequency score x Duration score=Total CAF score | 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) | The DCFS-R is measured as a total score from 4 to 20, with higher scores indicating more severe cognitive fluctuations in dementia. It is calculated by summing a nurse's ratings on four items, each scored on a 5-point Likert scale (1=no difference, 5=very large difference). The four items assess the difference between a person's best and worst functioning, which includes daytime somnolence, drowsiness, and altered levels of consciousness. | Screening, Baseline, ChEI Cohort Day 56, 1 year follow-up visit, and 2 year follow-up visit |
| Mayo Fluctuations Scale (Four questions) | The four questions included in the Mayo Fluctuations Scale have been found to significantly differentiate Alzheimer's Disease from DLB. Positive items are summed to create a "fluctuations composite score" with a score of 3 or 4 associated with DLB. | Screening, Baseline, ChEI Cohort Day 56, 1 year follow-up visit, and 2 year follow-up visit |
| Functional Activities Questionnaire (FAQ Assessment) | The FAQ is a number from 0 to 30 that represents a person's independence in daily tasks, with higher scores indicating more difficulty. The score is calculated by summing the ratings (0-3) for 10 activities, and a cut-off score of 9 or higher is often used to suggest potential cognitive or functional impairment. |
Not provided
Not provided
Inclusion Criteria:
Arm 1:
Exclusion Criteria:
Arm 1
Inclusion Criteria:
Arm 2 (Cholinesterase inhibitor cohort) inclusion criteria:
Exclusion Criteria:
Arm 2 (Cholinesterase inhibitor cohort) exclusion criteria:
Inclusion criteria:
Arm 3 (Healthy Controls)
Exclusion Criteria:
Arm 3 (Healthy Controls)
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Kara McHaney | Contact | (804) 828-4788 | Kara.McHaney@vcuhealth.org |
| Name | Affiliation | Role |
|---|---|---|
| Matthew Barrett | Virginia Commonwealth University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Virginia Commonwealth University | Recruiting | Richmond | Virginia | 23298 | United States |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
A cross-sectional case control study in which cholinergic degeneration in 45 subjects with DLB or PDD with CF will be compared to a group of 45 subjects with Lewy Body disease without CF and 30 healthy controls. The first 20 participants who are eligible and consent will also participate in an 8-week pre-post interventional cohort study.
Not provided
Not provided
Not provided
Not provided
| 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. |
|
| Screening, Baseline, 1 year follow-up visit, and 2 year follow-up visit |
| Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) | The MDS-UPDRS is a tool that measures the experiences of daily living (Part I), motor experiences of daily living (Part II), motor examination (Part III), and motor complications (Part IV). Scores range from 0 to 260, with 0 indicating no disability and higher scores indicating greater disability. The individual parts are rated on a scale of 0 to 4, with higher scores indicating greater impairment. | Screening, Baseline, 1 year follow-up visit, and 2 year follow-up visit |
| REM Sleep Behavior Disorder Questionnaire (RBDSQ) | The RBDSQ is measured by a total from 0-13, with a score of 5 or higher indicating a positive result for REM Sleep Behavior Disorder (RBD). The questionnaire is a 10-item self-rating tool to screen for RBD, and the cutoff score can vary depending on the population being screened. | Screening, Baseline, 1 year follow-up visit, and 2 year follow-up visit |
| Neuropsychiatric Inventory (NPI) | The NPI is an interview performed with a caregiver to assess any changes in the participants' behavior related to delusions, hallucinations, anxiety, and apathy. It is comprised of 4 main questions, 31 sub-questions and frequency/severity ratings. | Screening, Baseline, 1 year follow-up visit, and 2 year follow-up visit |
| Enhanced Scale for the assessment for Parkinson's Disease (SAPS-PD) | The eSAPS-PD is used to measure the severity of hallucinations and delusions in patients with Parkinson's Disease Psychosis (PDP). Scored on a scale of 0 to 5 for each of its 9 items, resulting in a total score from 0 to 45. Each item is rated based on the severity of the symptom, with a score of 0 meaning "None" and a score of 5 meaning "Severe". | Screening, Baseline, 1 year follow-up visit, and 2 year follow-up visit |
| Patient Health Questionnaire-9 (PHQ-9) | The PHQ-9 is a self-report measure used to screen for and assess the severity of depression in adults. It consists of nine questions based on the diagnostic criteria for major depressive disorder in the DSM-5. The total score for the PHQ-9 can range from 0 to 27. Each of the nine items is scored based on the frequency with which a person has experienced a specific symptom over the past two weeks: 0: Not at all, 1: Several days, 2: More than half the days, 3: Nearly every day. The scores for all nine items are added together to produce a total severity score. While scores of 10 or higher have high sensitivity and specificity for identifying major depression, the PHQ-9 alone is not a diagnostic tool. A clinical interview is necessary for a definitive diagnosis. | Screening, Baseline, 1 year follow-up visit, and 2 year follow-up visit |
| ID | Term |
|---|---|
| D020961 | Lewy Body Disease |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D003704 | Dementia |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided