Imaging a Cholinergic Biomarker of Cognition in Parkinson's Disease

Parkinson's Disease Clinical Trial

Official title:

Imaging a Cholinergic Biomarker of Cognition in Parkinson's Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05034263
• Other study ID #: 2020-00669
• Status: Recruiting
• Start date: May 27, 2021
• Est. completion date: May 27, 2024

Study information

• Verified date: October 2022
• Source: Stony Brook University
• Contact: Sandra Skinner, PhD
• Phone: 631-444-7513
• Email: sandra.skinner[@]stonybrookmedicine.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: May 27, 2024
• Est. primary completion date: May 27, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Locations

Country	Name	City	State
United States	Stony Brook Medical Center	Stony Brook	New York

Sponsors (2)

Lead Sponsor	Collaborator
Stony Brook University	Parkinson's Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cholinergic terminal density at baseline	Measured by PET scan 18F[VAT] distribution volume	Baseline
Primary	Cholinergic terminal density change between baseline and 18-months follow-up	Measured by the difference in PET scan 18F[VAT] distribution volume at baseline and 18-months follow-up	Baseline and 18 months follow-up
Primary	Overall cognitive functioning at baseline	As measured by the Montreal Cognitive Assessment (MoCA). The MoCA measures eight domains commonly affected by mild cognitive impairment. The one-page 30-point test includes assessments of short-term and delayed memory recall, visuospatial abilities, language, orientation to time and space, and executive functions including attention, concentration, and working memory. The MoCA has been shown to be sensitive to change over time. Scores on the MocA range from 0-30 with higher scores indicating better cognitive functioning.	Baseline
Primary	Change in overall cognitive functioning	As measured by the difference between the Montreal Cognitive Assessment (MoCA) score at baseline and at 18-months follow-up.The MoCA measures eight domains commonly affected by mild cognitive impairment. The one-page 30-point test includes assessments of short-term and delayed memory recall, visuospatial abilities, language, orientation to time and space, and executive functions including attention, concentration, and working memory. The MoCA has been shown to be sensitive to change over time. Scores on the MocA range from 0-30 with higher scores indicating better cognitive functioning.	Baseline and 18 Months
Primary	Attention/working memory at baseline as measured by the Trail Making A Test	The Trail Making Test is a quickly and easily administered test which assesses cognitive abilities such as visual-conceptual and visual-motor tracking, sustained attention, and task alternation abilities. Administration time for the Trail Making Test A is 5 minutes.	Baseline
Primary	Attention/working memory change from baseline to 18-months follow-up as measured by the Trail Making A Test	The Trail Making Test is a quickly and easily administered test which assesses cognitive abilities such as visual-conceptual and visual-motor tracking, sustained attention, and task alternation abilities. Administration time for the Trail Making Test A is 5 minutes.	18 months
Primary	Attention/working memory at baseline as measured by the Symbol Digit Modalities Test (SDMT)	Symbol Digit Modalities Test (SDMT) takes five minutes to complete and has demonstrated sensitivity in detecting changes in cognitive functioning over time.	Baseline
Primary	Attention/working memory change from baseline to 18-months follow-up as measured by the Symbol Digit Modalities Test	Symbol Digit Modalities Test (SDMT) takes five minutes to complete and has demonstrated sensitivity in detecting changes in cognitive functioning over time.	Baseline and 18- months follow-up
Primary	Executive function at baseline as measured by the Clock Drawing Test	The Clock Drawing Test is a quick screening test for cognitive dysfunction secondary to a range of neurological disorders and takes less than 5 minutes to administer.	Baseline
Primary	Executive function change from baseline to 18-months follow-up as measured by the Clock Drawing Test	The Clock Drawing Test is a quick screening test for cognitive dysfunction secondary to a range of neurological disorders and takes less than 5 minutes to administer.	Baseline and 18-month follow-up
Primary	Executive function at baseline as measured by the Trail Making Test B	The Trail Making Test is a quickly and easily administered test which assesses cognitive abilities such as visual-conceptual and visual-motor tracking, sustained attention, and task alternation abilities. Administration time for the Trail Making Test B is 10 minutes.	Baseline
Primary	Executive function change from baseline to 18-months follow-up as measured by the Trail Making Test B	The Trail Making Test is a quickly and easily administered test which assesses cognitive abilities such as visual-conceptual and visual-motor tracking, sustained attention, and task alternation abilities. Administration time for the Trail Making Test B is 10 minutes.	Baseline and 18-month follow-up
Primary	Language at baseline as measured by the Animal Naming Test	The Animal Naming Test is a semantic fluency test that takes one minute to administer.	Baseline
Primary	Language change from baseline to 18-month follow-up as measured by the Animal Naming Test	The Animal Naming Test is a semantic fluency test that takes one minute to administer.	Baseline and 18-months follow-up
Primary	Language at baseline as measured by the Boston Naming Test	The Boston Naming Test measures confrontational word retrieval and takes about 15 minutes to administer.	Baseline
Primary	Language change from baseline to 18-months follow-up as measured by the Boston Naming Test	The Boston Naming Test measures confrontational word retrieval and takes about 15 minutes to administer.	Baseline and 18-months follow-up
Primary	Language change between baseline and 18-month follow-up as measured by the Boston Naming Test	The Boston Naming Test measures confrontational word retrieval and takes about 15 minutes to administer.	Baseline
Primary	Memory at baseline as measured by the Free and Cued Selective Reminding Test	The Free and Cued Selective Reminding Test is an episodic memory test which assesses immediate and delayed free and cued-facilitated recall.	Baseline
Primary	Memory change from baseline to 18-months follow-up as measured by the Free and Cued Selective Reminding Test	The Free and Cued Selective Reminding Test is an episodic memory test which assesses immediate and delayed free and cued-facilitated recall.	Baseline and 18-months follow-up
Primary	Memory at baseline as measured by the Brief Visuospatial Memory Test-Revised Selective Reminding Test	The Brief Visuospatial Memory Test-Revised is a brief measure of visuospatial memory that takes approximately 45 minutes to administer.	Baseline
Primary	Memory change from baseline to 18-months follow-up as measured by the Brief Visuospatial Memory Test-Revised	The Brief Visuospatial Memory Test-Revised is a brief measure of visuospatial memory that takes approximately 45 minutes to administer.	Baseline and 18-months follow-up
Primary	Memory change between baseline and 18-month follow-up	As measured by the change in Free and Cued Selective Reminding Test and the Brief Visuospatial Memory Test-Revised scores at baseline and at 18-months follow-up.	Baseline and 18-month follow-up
Primary	Visuospatial at baseline as measured by the Judgement of Line Orientation Test	Judgement of Line Orientation measures visuospatial perception and takes less than 15 minutes to administer.	Baseline
Primary	Visuospatial change from baseline to 18-months follow-up as measured by the Judgement of Line Orientation Test	Judgement of Line Orientation measures visuospatial perception and takes less than 15 minutes to administer.	Baseline and 18-months follow-up
Primary	Visuospatial at baseline as measured by the Intersecting Pentagons Test	Intersecting Pentagons is a measure of visuospatial sense that takes less than 5 minutes to administer.	Baseline
Primary	Visuospatial change from baseline to 18-months follow-up as measured by the Intersecting Pentagons Test	Intersecting Pentagons is a measure of visuospatial perception that takes less than 5 minutes to administer.	Baseline and 18-months follow-up
Primary	Estrogen levels in blood at baseline	Estrogen levels (picograms of estradiol per milliliter of serum) will be measured via blood draw performed at baseline	Baseline
Primary	Progesterone levels in blood as baseline	Progesterone levels (nanograms of progesterone per milliliter of serum) will be measured via blood draw at baseline	Baseline
Primary	Testosterone levels in blood at baseline	Levels of free testosterone (picograms testosterone per milliliter serum) and total testosterone (nanograms testosterone/deciliter serum) will be measured via blood draw performed at the baseline visit.	Baseline
Secondary	Cholinergic terminal binding potential at baseline	Measured by PFC [18F]VAT VT and BPND	Baseline
Secondary	Cholinergic terminal binding potential change between baseline and 18-months follow-up	Measured by PFC [18F]VAT VT and BPND	Baseline and 18-month follow-up
Secondary	MRI Fractional anisotropy (FA) Values at baseline	As measured by fMRI at baseline	Baseline
Secondary	Change in MRI Fractional anisotropy (FA) Values from baseline to 18-months follow-up	As measured by fMRI at baseline and 18-months follow-up	Baseline and 18-months follow-up
Secondary	MRI Resting-state functional connectivity at baseline	As measured by fMRI	Baseline
Secondary	MRI Resting-state functional connectivity change between baseline and 18-months follow-up	As measured by fMRI	Baseline and 18-months follow-up