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Istradefylline for Parkinson Disease With Cognitive Impairment

Primary Purpose

Parkinson Disease, Cognitive Impairment

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Istradefylline
Sponsored by
Virginia Commonwealth University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Parkinson Disease

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Meet criteria for probable Parkinson disease dementia or PD-MCI (mild cognitive impairment)
  • Age greater than 50
  • Hoehn and Yahr stage < 4 in "on" state
  • Currently taking carbidopa/levodopa
  • Antiparkinsonian medications stable for at least 4 weeks prior to baseline visit
  • Cholinesterase inhibitor dose stable for 8 weeks prior to baseline visit

Exclusion Criteria:

  • Meet criteria for dementia with Lewy bodies, including dementia onset prior to or within 1 year of parkinsonism onset
  • Presence of troublesome dyskinesias
  • Pregnancy or possibility of becoming pregnant during the study period.
  • Moderate or severe hepatic impairment
  • dementia too severe to complete study measures or to adhere to medication schedule

Sites / Locations

  • Virginia Commonwealth UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Usual care plus istradefylline

Arm Description

Participants will receive usual care, and in addition, will be asked to take istradefylline daily for 26 weeks.

Outcomes

Primary Outcome Measures

Change in executive function - Card Sort test
Executive function will be assessed using the Card Sort Test from the NIH Toolbox Cognition Battery. Participants will be assessed at baseline, 4 weeks, 14 weeks, and 26 weeks

Secondary Outcome Measures

Change in neurocognitive outcomes
NIH Toolbox Cognition Battery (NTCB) consists of multiple self-report and clinician reported tests. The assessments can be completed on a tablet device and a composite as well as sub-scores are calculated. Higher scores are indicative of better functioning. Participants will be assessed at baseline, 4 weeks, 14 weeks, and 26 weeks.
Change in recall
Immediate and delayed recall will be assessed using the Hopkins Verbal Learning Test - Revised, which will be administered by a trained clinician. Higher scores indicate better recall. Participants will be assessed at baseline, 4 weeks, 14 weeks, and 26 weeks.
Change in oral fluency
In the Controlled Oral Word Association Test (FAS, animals) (COWAT) the participant is asked to make verbal associations to different letters of the alphabet by saying all the words which they can think of beginning with a given letter. Higher scores indicate better oral fluency. Participants will be assessed at baseline, 4 weeks, 14 weeks, and 26 weeks.
Change in executive function - Trail Making Test
Participants will complete the Trail Making Test (TMT) which is a timed test of executive function. Scores are the number of seconds needed to complete the test with higher scores indicate poorer executive function. Participants will be assessed at baseline, 4 weeks, 14 weeks, and 26 weeks.
Change in cognitive status
Participant's cognitive status will be assessed using the Montreal Cognitive Assessment score. Higher scores indicated better cognitive status. Participants will be assessed at baseline, 4 weeks, 14 weeks, and 26 weeks.
Change in higher cortical functions
The Dementia Rating Scale-2 (DRS-2) measures deficits in a large range of higher cortical functions and differentiates deficits of varying severity levels. The DRS-2 yields five subscales as well as an overall cognitive functioning score. Higher scores higher impairment. Participants will be assessed at baseline, 4 weeks, 14 weeks, and 26 weeks
Change in clinical symptoms related to Parkinson disease
The MDS-UPDRS has four parts, and is obtained via a combination of structured interview, questionnaire, and physical exam specifically assessing motor aspects of Parkinson disease. Higher scores indicate more severe clinical symptoms. Participants will be assessed at baseline, 4 weeks, 14 weeks, and 26 weeks.
Change in Parkinson disease stage
The Hoehn & Yahr scale will be used to assess functional disability associated with progression of Parkinson's disease through various stages. Later (higher) stages indicate more severe cases. Participants will be assessed at baseline, 4 weeks, 14 weeks, and 26 weeks
Change in Schwab and England ADL score
Schwab & England Activities of Daily Living Scale estimates the abilities of individuals living with Parkinson's Disease relative to a completely independent situation. The examiner prompts the individual to select the rating that most accurately describes their level of functional independence and frequently incorporates the caregiver's ratings of patient's level of independence as well. It is rated in 10% increments with 100% being completely independent and 0% being vegetative. Participants will be assessed at baseline, 4 weeks, 14 weeks, and 26 weeks
Change in hours of "off" time
Participants (and/or caregivers) will complete daily Hauser diaries reporting motor symptoms of Parkinson Disease. Diaries will be used to calculate many hours participants spend in "off" episodes (periods where symptoms recur) during awake time.
Change in percentage of "off" time
Participants (and/or caregivers) will complete daily Hauser diaries reporting motor symptoms of Parkinson Disease. Diaries will be used to calculate the percentage of awake time participants spend in "off" episodes (periods where symptoms recur).
Change in hours of "on" time
Participants (and/or caregivers) will complete daily Hauser diaries reporting motor symptoms of Parkinson Disease. Diaries will be used to calculate many hours participants spend in "on" episodes (periods where levodopa has a positive effect on Parkinson's symptoms) during awake time. The diaries will be used to assess daily awake time spent in the "on" state with dyskinesia, in the "on" state with non-troublesome dyskinesia, in the "on" state with troublesome dyskinesia, and in the "on" state with without troublesome dyskinesia.
Change in percentage of "on" time
Participants (and/or caregivers) will complete daily Hauser diaries reporting motor symptoms of Parkinson Disease. Diaries will be used to calculate the percentage of awake time participants spend in "on" episodes (periods where levodopa has a positive effect on Parkinson's symptoms). The diaries will be used to assess percentage of daily awake time spent in the "on" state with dyskinesia, in the "on" state with non-troublesome dyskinesia, in the "on" state with troublesome dyskinesia, and in the "on" state with without troublesome dyskinesia.
Change in severity of illness
The Clinical Global Impression Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. The score is based on a semi-structured interview assessing multiple aspects of function impacted by PD. Higher scores indicate more severe illness. Participants will be assessed at baseline, 4 weeks, 14 weeks, and 26 weeks
Change in Parkinson's health status
The PDQ-39 is the most widely used Parkinson's specific measure of health status. This is a 39-item questionnaire that offers a patient reported measure of health status and quality of life and assesses how often people affected by Parkinson's experience difficulties across 8 dimensions of daily living including mobility, activities of daily living (ADLs), emotional wellbeing, stigma, social support, cognition, communication and bodily support. Lower scores indicate better quality of life. Participants will be assessed at baseline, 4 weeks, 14 weeks, and 26 weeks

Full Information

First Posted
April 11, 2022
Last Updated
July 21, 2023
Sponsor
Virginia Commonwealth University
Collaborators
Kyowa Kirin, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05333549
Brief Title
Istradefylline for Parkinson Disease With Cognitive Impairment
Official Title
Istradefylline for Parkinson Disease Cognitive Impairment
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 18, 2022 (Actual)
Primary Completion Date
July 2025 (Anticipated)
Study Completion Date
July 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Virginia Commonwealth University
Collaborators
Kyowa Kirin, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No

5. Study Description

Brief Summary
The purpose of this research study is to determine whether istradefylline improves cognition in individuals with Parkinson disease with cognitive impairment.
Detailed Description
Istradefylline has been approved by the U. S. Food and Drug Administration (FDA) to reduce "off" episodes in Parkinson disease. The period when levodopa has a positive effect on Parkinson's symptoms is called on-time. Once the medication stops working, a so called "off" episode starts, where symptoms recur. Usual care for treatment of Parkinson disease with cognitive impairment is use of cognition enhancing medications also called cholinesterase inhibitors. In this study, participants will receive usual care, and in addition, they will be asked to take istradefylline daily for 26 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease, Cognitive Impairment

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Usual care plus istradefylline
Arm Type
Experimental
Arm Description
Participants will receive usual care, and in addition, will be asked to take istradefylline daily for 26 weeks.
Intervention Type
Drug
Intervention Name(s)
Istradefylline
Intervention Description
2 weeks on istradefylline 20mg daily, 2 weeks on istradefylline 40mg with the ability to adjust other antiparkinsonian medications, and 22 weeks on istradefylline 40mg and stable antiparkinsonian medications
Primary Outcome Measure Information:
Title
Change in executive function - Card Sort test
Description
Executive function will be assessed using the Card Sort Test from the NIH Toolbox Cognition Battery. Participants will be assessed at baseline, 4 weeks, 14 weeks, and 26 weeks
Time Frame
Baseline to 26 weeks
Secondary Outcome Measure Information:
Title
Change in neurocognitive outcomes
Description
NIH Toolbox Cognition Battery (NTCB) consists of multiple self-report and clinician reported tests. The assessments can be completed on a tablet device and a composite as well as sub-scores are calculated. Higher scores are indicative of better functioning. Participants will be assessed at baseline, 4 weeks, 14 weeks, and 26 weeks.
Time Frame
Baseline to 26 weeks
Title
Change in recall
Description
Immediate and delayed recall will be assessed using the Hopkins Verbal Learning Test - Revised, which will be administered by a trained clinician. Higher scores indicate better recall. Participants will be assessed at baseline, 4 weeks, 14 weeks, and 26 weeks.
Time Frame
Baseline to 26 weeks
Title
Change in oral fluency
Description
In the Controlled Oral Word Association Test (FAS, animals) (COWAT) the participant is asked to make verbal associations to different letters of the alphabet by saying all the words which they can think of beginning with a given letter. Higher scores indicate better oral fluency. Participants will be assessed at baseline, 4 weeks, 14 weeks, and 26 weeks.
Time Frame
Baseline to 26 weeks
Title
Change in executive function - Trail Making Test
Description
Participants will complete the Trail Making Test (TMT) which is a timed test of executive function. Scores are the number of seconds needed to complete the test with higher scores indicate poorer executive function. Participants will be assessed at baseline, 4 weeks, 14 weeks, and 26 weeks.
Time Frame
Baseline to 26 weeks
Title
Change in cognitive status
Description
Participant's cognitive status will be assessed using the Montreal Cognitive Assessment score. Higher scores indicated better cognitive status. Participants will be assessed at baseline, 4 weeks, 14 weeks, and 26 weeks.
Time Frame
Baseline to 26 weeks
Title
Change in higher cortical functions
Description
The Dementia Rating Scale-2 (DRS-2) measures deficits in a large range of higher cortical functions and differentiates deficits of varying severity levels. The DRS-2 yields five subscales as well as an overall cognitive functioning score. Higher scores higher impairment. Participants will be assessed at baseline, 4 weeks, 14 weeks, and 26 weeks
Time Frame
Baseline to 26 weeks
Title
Change in clinical symptoms related to Parkinson disease
Description
The MDS-UPDRS has four parts, and is obtained via a combination of structured interview, questionnaire, and physical exam specifically assessing motor aspects of Parkinson disease. Higher scores indicate more severe clinical symptoms. Participants will be assessed at baseline, 4 weeks, 14 weeks, and 26 weeks.
Time Frame
Baseline to 26 weeks
Title
Change in Parkinson disease stage
Description
The Hoehn & Yahr scale will be used to assess functional disability associated with progression of Parkinson's disease through various stages. Later (higher) stages indicate more severe cases. Participants will be assessed at baseline, 4 weeks, 14 weeks, and 26 weeks
Time Frame
Baseline to 26 weeks
Title
Change in Schwab and England ADL score
Description
Schwab & England Activities of Daily Living Scale estimates the abilities of individuals living with Parkinson's Disease relative to a completely independent situation. The examiner prompts the individual to select the rating that most accurately describes their level of functional independence and frequently incorporates the caregiver's ratings of patient's level of independence as well. It is rated in 10% increments with 100% being completely independent and 0% being vegetative. Participants will be assessed at baseline, 4 weeks, 14 weeks, and 26 weeks
Time Frame
Baseline to 26 weeks
Title
Change in hours of "off" time
Description
Participants (and/or caregivers) will complete daily Hauser diaries reporting motor symptoms of Parkinson Disease. Diaries will be used to calculate many hours participants spend in "off" episodes (periods where symptoms recur) during awake time.
Time Frame
Baseline to 26 weeks
Title
Change in percentage of "off" time
Description
Participants (and/or caregivers) will complete daily Hauser diaries reporting motor symptoms of Parkinson Disease. Diaries will be used to calculate the percentage of awake time participants spend in "off" episodes (periods where symptoms recur).
Time Frame
Baseline to 26 weeks
Title
Change in hours of "on" time
Description
Participants (and/or caregivers) will complete daily Hauser diaries reporting motor symptoms of Parkinson Disease. Diaries will be used to calculate many hours participants spend in "on" episodes (periods where levodopa has a positive effect on Parkinson's symptoms) during awake time. The diaries will be used to assess daily awake time spent in the "on" state with dyskinesia, in the "on" state with non-troublesome dyskinesia, in the "on" state with troublesome dyskinesia, and in the "on" state with without troublesome dyskinesia.
Time Frame
Baseline to 26 weeks
Title
Change in percentage of "on" time
Description
Participants (and/or caregivers) will complete daily Hauser diaries reporting motor symptoms of Parkinson Disease. Diaries will be used to calculate the percentage of awake time participants spend in "on" episodes (periods where levodopa has a positive effect on Parkinson's symptoms). The diaries will be used to assess percentage of daily awake time spent in the "on" state with dyskinesia, in the "on" state with non-troublesome dyskinesia, in the "on" state with troublesome dyskinesia, and in the "on" state with without troublesome dyskinesia.
Time Frame
Baseline to 26 weeks
Title
Change in severity of illness
Description
The Clinical Global Impression Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. The score is based on a semi-structured interview assessing multiple aspects of function impacted by PD. Higher scores indicate more severe illness. Participants will be assessed at baseline, 4 weeks, 14 weeks, and 26 weeks
Time Frame
Baseline to 26 weeks
Title
Change in Parkinson's health status
Description
The PDQ-39 is the most widely used Parkinson's specific measure of health status. This is a 39-item questionnaire that offers a patient reported measure of health status and quality of life and assesses how often people affected by Parkinson's experience difficulties across 8 dimensions of daily living including mobility, activities of daily living (ADLs), emotional wellbeing, stigma, social support, cognition, communication and bodily support. Lower scores indicate better quality of life. Participants will be assessed at baseline, 4 weeks, 14 weeks, and 26 weeks
Time Frame
Baseline to 26 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Meet criteria for probable Parkinson disease dementia or PD-MCI (mild cognitive impairment) Age greater than 50 Hoehn and Yahr stage < 4 in "on" state Currently taking carbidopa/levodopa Antiparkinsonian medications stable for at least 4 weeks prior to baseline visit Cholinesterase inhibitor dose stable for 8 weeks prior to baseline visit Exclusion Criteria: Meet criteria for dementia with Lewy bodies, including dementia onset prior to or within 1 year of parkinsonism onset Presence of troublesome dyskinesias Pregnancy or possibility of becoming pregnant during the study period. Moderate or severe hepatic impairment dementia too severe to complete study measures or to adhere to medication schedule
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kara McHaney
Phone
804-828-4788
Email
kara.mchaney@vcuhealth.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthew Barrett, MD
Organizational Affiliation
Virginia Commonwealth University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kara McHaney
Phone
804-828-4788
Email
kara.mchaney@vcuhealth.org

12. IPD Sharing Statement

Plan to Share IPD
No

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Istradefylline for Parkinson Disease With Cognitive Impairment

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