Clinical trial NCT05034263: Imaging a Cholinergic Biomarker of Cognition in Parkinson's Disease
Official title: Imaging a Cholinergic Biomarker of Cognition in Parkinson's Disease
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Parkinson's Disease
Keywords: Acetylcholine
PET
MRI
Lead sponsor: Stony Brook University
Sponsor class: OTHER
Collaborators: name: Parkinson's Foundation
First posted: 2021-09-05
Enrollment: 6
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: People with Parkinson's disease who have normal cognition or mild cognitive impairment

Brief summary: This is an imaging study designed to illuminate the function of the cholinergic system and its association with cognitive skills in people with Parkinson's disease. The hypothesis of this study is that there will be an association between cholinergic terminal density, sex hormones, and cognitive functioning. Participants will receive a PET and MRI scan along with a battery of neurocognitive tests at baseline and again at 18 months follow-up. Hormone levels will be measured at baseline.

Detailed description: This is an imaging study designed to illuminate the functioning of the cholinergic system in people with Parkinson's disease. Some people with Parkinson's disease develop trouble with certain aspects of thinking such as memory. Studies have shown an association between a decline in thinking skills and dysfunction of the cholinergic system. This study will use the novel PET tracer \[18F\]VAT to provide more specific information about how the cholinergic system works by enabling direct measurement of cholinergic terminal density and projections. The hypothesis of this study is that there will be an association between cholinergic terminal density, sex hormones, and cognitive functioning. This is a longitudinal observational study that involves a screening visit and four study visits over the course of 18 months. The visits consist of neurocognitive assessments and imaging (MRI and PET scans) administered at baseline and at 18 months follow-up. Hormone levels will also be measured at baseline. This study is open to people with Parkinson's disease who have either normal cognition or mild cognitive impairment.

Eligibility criteria: Inclusion Criteria:

* Age 50-80
* Diagnosis of Parkinson's disease
* Ability to provide informed consent
* Ability to speak English
* Normal cognition or mild cognitive impairment
* Willingness to go off parkinsonian medication for 12 hours prior to two of the study visits

Exclusion Criteria:

* Contraindication for MRI
* Abnormal clinical brain MRI, specifically with evidence of large-vessel stroke or mass lesion
* History of stereotactic or ablative brain surgery
* Pregnancy
* Recent participation in other research studies involving radiation such that the annual research radiation dose would exceed FDA Limit if participating in this study
* Prior brain injury (eg., TBI)
* Baseline cognitive impairment due to genetic or developmental disorder
* Active illicit drug use or alcohol abuse
* Incapable of staying still for a 2-hour PET or MRI study
* Use of CNS-penetrating medications affecting the cholinergic system, including cholinesterase inhibitors and anticholinergics, up to 60 days prior to study participation

Primary outcomes:
measure: Cholinergic terminal density at baseline
timeFrame: Baseline
measure: Cholinergic terminal density change between baseline and 18-months follow-up
timeFrame: Baseline and 18 months follow-up
measure: Overall cognitive functioning at baseline
timeFrame: Baseline
measure: Change in overall cognitive functioning
timeFrame: Baseline and 18 Months
measure: Attention/working memory at baseline as measured by the Trail Making A Test
timeFrame: Baseline
measure: Attention/working memory change from baseline to 18-months follow-up as measured by the Trail Making A Test
timeFrame: 18 months
measure: Attention/working memory at baseline as measured by the Symbol Digit Modalities Test (SDMT)
timeFrame: Baseline
measure: Attention/working memory change from baseline to 18-months follow-up as measured by the Symbol Digit Modalities Test
timeFrame: Baseline and 18- months follow-up
measure: Executive function at baseline as measured by the Clock Drawing Test
timeFrame: Baseline
measure: Executive function change from baseline to 18-months follow-up as measured by the Clock Drawing Test
timeFrame: Baseline and 18-month follow-up
measure: Executive function at baseline as measured by the Trail Making Test B
timeFrame: Baseline
measure: Executive function change from baseline to 18-months follow-up as measured by the Trail Making Test B
timeFrame: Baseline and 18-month follow-up
measure: Language at baseline as measured by the Animal Naming Test
timeFrame: Baseline
measure: Language change from baseline to 18-month follow-up as measured by the Animal Naming Test
timeFrame: Baseline and 18-months follow-up
measure: Language at baseline as measured by the Boston Naming Test
timeFrame: Baseline
measure: Language change from baseline to 18-months follow-up as measured by the Boston Naming Test
timeFrame: Baseline and 18-months follow-up
measure: Language change between baseline and 18-month follow-up as measured by the Boston Naming Test
timeFrame: Baseline
measure: Memory at baseline as measured by the Free and Cued Selective Reminding Test
timeFrame: Baseline
measure: Memory change from baseline to 18-months follow-up as measured by the Free and Cued Selective Reminding Test
timeFrame: Baseline and 18-months follow-up
measure: Memory at baseline as measured by the Brief Visuospatial Memory Test-Revised Selective Reminding Test
timeFrame: Baseline
measure: Memory change from baseline to 18-months follow-up as measured by the Brief Visuospatial Memory Test-Revised
timeFrame: Baseline and 18-months follow-up
measure: Memory change between baseline and 18-month follow-up
timeFrame: Baseline and 18-month follow-up
measure: Visuospatial at baseline as measured by the Judgement of Line Orientation Test
timeFrame: Baseline
measure: Visuospatial change from baseline to 18-months follow-up as measured by the Judgement of Line Orientation Test
timeFrame: Baseline and 18-months follow-up
measure: Visuospatial at baseline as measured by the Intersecting Pentagons Test
timeFrame: Baseline
measure: Visuospatial change from baseline to 18-months follow-up as measured by the Intersecting Pentagons Test
timeFrame: Baseline and 18-months follow-up
measure: Estrogen levels in blood at baseline
timeFrame: Baseline
measure: Progesterone levels in blood as baseline
timeFrame: Baseline
measure: Testosterone levels in blood at baseline
timeFrame: Baseline
Secondary outcomes:
measure: Cholinergic terminal binding potential at baseline
timeFrame: Baseline
measure: Cholinergic terminal binding potential change between baseline and 18-months follow-up
timeFrame: Baseline and 18-month follow-up
measure: MRI Fractional anisotropy (FA) Values at baseline
timeFrame: Baseline
measure: Change in MRI Fractional anisotropy (FA) Values from baseline to 18-months follow-up
timeFrame: Baseline and 18-months follow-up
measure: MRI Resting-state functional connectivity at baseline
timeFrame: Baseline
measure: MRI Resting-state functional connectivity change between baseline and 18-months follow-up
timeFrame: Baseline and 18-months follow-up
Other outcomes:
Locations:
city: Stony Brook
country: United States
facility: Stony Brook Medical Center
state: New York
Study officials:
affiliation: Stony Brook Medical Center
name: Chuan Huang, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stony Brook Medical Center
name: Carine Maurer, PhD
role: PRINCIPAL_INVESTIGATOR
References: