Parkinson DiseasePhase 2NCT05333549
Istradefylline for Parkinson Disease With Cognitive Impairment
A Phase 2 study testing Istradefylline medication in people with Parkinson Disease and Cognitive Impairment, run by Virginia Commonwealth University at 1 site in United States.
Trial summary
The purpose of this research study is to determine whether istradefylline improves cognition in individuals with Parkinson disease with cognitive impairment. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Parkinson Disease, Cognitive Impairment
- What is being tested?
- Istradefylline medication
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Jul 2022to 9 Jun 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Virginia Commonwealth University
Richmond, Virginia, 23298
About this study
Official title: Istradefylline for Parkinson Disease Cognitive Impairment
The purpose of this research study is to determine whether istradefylline improves cognition in individuals with Parkinson disease with cognitive impairment.
Read the 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.
- Conditions
- Parkinson Disease, Cognitive Impairment
- Being tested
- Istradefylline medication
- Medical subject headings
- Parkinson Disease, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Istradefylline medicationDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Usual care plus istradefylline | Experimental | Participants will receive usual care, and in addition, will be asked to take istradefylline daily for 26 weeks. Receives: Drug: Istradefylline medication |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Executive Function - Card Sort Test
Executive function will be assessed using the Card Sort Test from the NIH Toolbox Cognition Battery. It measures the number of times the participant successfully figures out the rule and matches 10 cards in a row (maximum of 6). So the score range is 0-6. Interpretation: Low numbers (e.g., 0-2 categories) reflect poor abstract reasoning and an inability to use feedback to guide behavior. A score of 6 is the standard normal score for younger adults and a score of 3 or higher is normal or adjusted cut-off for adults 60+.
Measured: Baseline to 26 weeks
Secondary outcomes (6)
Change in Neurocognitive Outcomes
NIH Toolbox Cognition Battery (NTCB): Scores are reported as T-scores normed to a mean of 50 with a standard deviation (SD) of 10, with higher scores indicating better cognitive functioning. In this dataset, the lowest T-score was 28 and the highest T-score was 66.
Measured: Baseline to 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. aw metrics must be converted into standard scores because raw totals decrease naturally with normal aging. Examiners utilize the normative data inside the Official PAR HVLT-R Manual Supplement or automated PARiConnect software to convert raw metrics into T-scores. T-scores adjust for age (and sometimes gender and education level depending on the specific norming data used). T-Score Range: Typically spans from 20 to 80. Average Performance: 40 to 59, Borderline/Low Range: 30 to 39, Clinical Impairment: Below 30
Measured: Baseline to 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. Because it is a free-generation task, there is no formal maximum "ceiling" score, but performance typically falls into predictable ranges. Average Performance: Healthy young-to-middle-aged adults typically generate an aggregate total of 35 to 45 words across all three letters combined. Scoring beneath the 25th percentile suggests a low-average performance. If the trajectory drops significantly further-specifically below the 5th percentile (equivalent to ≤ 1.5 standard deviations under the median)-clinicians look closely for signs of mild cognitive impairment (MCI), aphasia, or neurodegenerative conditions.
Measured: Baseline to 26 weeks
Change in Executive Function - Trail Making Test
TMT which is a timed test of attention and executive function.It primarily assesses visual scanning, attention, and processing speed and requires participants to connect numbered targets in sequential order. It additionally assesses cognitive flexibility and executive function and requires participants to alternate between numbers and letters in sequential order. Raw scores are the number of seconds needed to complete the test with higher scores indicating poorer executive function. A standard cutoff or cap is typically applied at 300 seconds (5 minutes) per section to halt the test if a patient struggles. The raw scores are converted into T-scores based on Heaton norms for age, sex, race, and education. T-scores have a mean of 50 and standard deviation (SD) of 10, with higher T-scores indicating better performance. T-scores ≥40 are generally considered within normal limits, while T-scores <40 indicate below-expected performance, with lower scores reflecting greater impai
Measured: Baseline to 26 weeks
Change in Cognitive Status-Montreal Cognitive Assessment
Participant's cognitive status will be assessed using the Montreal Cognitive Assessment score. Higher scores indicated better cognitive status. The Montreal Cognitive Assessment (MoCA) is scored between 0 and out of a maximum of 30 points, with a raw total score of 26 or above traditionally considered clinically normal. 18-25 points is considered Mild Cognitive Impairment (MCI), 10-17 points is considered Moderate Cognitive Impairment, and less than 10 is considered Severe Cognitive Impairment
Measured: Baseline to 26 weeks
Change in Higher Cortical Functions-The Dementia Rating Scale-2 (DRS-2)
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 Dementia Rating Scale-2 (DRS-2) is scored out of a maximum of 144 total raw points. A higher score indicates better cognitive function, while lower scores signify greater cognitive and behavioral impairment. 124-144 points indicated Normal/non-impaired, 120-123 Borderline/mild, less than 120 points Impaired. The maximum possible total score for the Dementia Rating Scale-2 (DRS-2) is 144, and the minimum possible total score is 0. There are five domains that equal 144 points. Each domain has a different maximum score, but they all have a minimum score of 0: Attention: Maximum score of 37, Initiation/Perseveration: Maximum score of 37, Construction: Maximum score of 6, Conceptualization: Maximum score of 39, Memory: Maximum score of 25.
Measured: Baseline to 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2022
- Study start18 Jul 2022
- Primary completion9 Jun 2025
- Study completion9 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- More trials run by Virginia Commonwealth UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Collaborators
- Kyowa Kirin, Inc.
- Responsible party
- Sponsor
- Investigators
- Matthew Barrett, MD, Principal investigator, Virginia Commonwealth University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05333549
- Sponsor's protocol ID
- HM20022119
- Status last verified
- Sep 2026
- First submitted
- 11 Apr 2022
- Last updated
- 23 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Istradefylline for Parkinson Disease Cognitive Impairment
- ClinicalTrials.gov ID
- NCT05333549
- Acronym / sponsor ID
- HM20022119
- Conditions
- Parkinson Disease, Cognitive Impairment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Collaborators
- Kyowa Kirin, Inc.
- Study start
- 18 Jul 2022 (actual)
- Primary completion
- 9 Jun 2025 (actual)
- Study completion
- 9 Jun 2025 (actual)
- First posted
- 19 Apr 2022 (actual)
- Results
- Posted 23 Sep 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Usual care plus istradefylline | Experimental | Drug: Istradefylline medicationParticipants will receive usual care, and in addition, will be asked to take istradefylline daily for 26 weeks. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Istradefylline medication2 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 | Drug | Usual care plus istradefylline |
Primary outcome
Change in Executive Function - Card Sort Test
Time frame: Baseline to 26 weeks
Executive function will be assessed using the Card Sort Test from the NIH Toolbox Cognition Battery. It measures the number of times the participant successfully figures out the rule and matches 10 cards in a row (maximum of 6). So the score range is 0-6. Interpretation: Low numbers (e.g., 0-2 categories) reflect poor abstract reasoning and an inability to use feedback to guide behavior. A score of 6 is the standard normal score for younger adults and a score of 3 or higher is normal or adjusted cut-off for adults 60+.
6 secondary outcomes
Change in Neurocognitive Outcomes
Time frame: Baseline to 26 weeks
Change in Recall
Time frame: Baseline to 26 weeks
Change in Oral Fluency
Time frame: Baseline to 26 weeks
Change in Executive Function - Trail Making Test
Time frame: Baseline to 26 weeks
Change in Cognitive Status-Montreal Cognitive Assessment
Time frame: Baseline to 26 weeks
Change in Higher Cortical Functions-The Dementia Rating Scale-2 (DRS-2)
Time frame: Baseline to 26 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Parkinson Disease
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
Enrolling by invitationObservational study
Early Molecular Biomarkers for Differentiating Parkinsonian Syndromes
PARKINSON DISEASE (Disorder), Atypical Parkinsonism
RecruitingPhase 3
A Clinical Study of Sacituzumab Tirumotecan (MK-2870) in Combination With Pembrolizumab (MK-3475) as First-line Maintenance Treatment of Cervical Cancer (MK-2870-036/TroFuse-036/GOG-3123/ENGOT-cx22)
Cervical Cancer
Active, not recruitingPhase 1/2
Clinical Safety and Efficacy of Umbilical Cord Mesenchymal Stromal Cells-derived Exosomes in Patients With Parkinson's Disease
Parkinson Disease (PD)
Active, not recruitingObservational study
Adaptive DBS to Offset STN Dysregulation During Exercise in PD
Parkinson Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthew Barrett, MD principal investigator
Virginia Commonwealth University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Istradefylline medication in people with Parkinson Disease and Cognitive Impairment, run by Virginia Commonwealth University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Sep 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Executive Function - Card Sort Test (time frame: Baseline to 26 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2026.