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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.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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

Other trials in United States

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.

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 groups in NCT05333549
Study groupRoleWhat they receive
Usual care plus istradefyllineExperimentalParticipants 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.

  1. 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)
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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.

  1. First posted19 Apr 2022
  2. Study start18 Jul 2022
  3. Primary completion9 Jun 2025
  4. Study completion9 Jun 2025

Resources

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)
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
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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.

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