Istradefylline for Parkinson's Disease with Cognitive Impairment

Overseen By Kara McHaney

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Virginia Commonwealth University

Must be taking: Carbidopa/levodopa

Disqualifiers: Dementia with Lewy bodies, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 26 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the drug istradefylline (also known as Nourianz or KW-6002) can improve thinking and memory in people with Parkinson's disease who experience memory or thinking problems. Participants will continue their usual treatment and add istradefylline daily for 26 weeks. Suitable candidates have Parkinson's disease with mild memory issues and are already taking medication such as carbidopa/levodopa. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that your antiparkinsonian medications and cholinesterase inhibitor doses are stable for a certain period before starting the trial.

Is there any evidence suggesting that istradefylline is likely to be safe for humans?

Research has shown that istradefylline is generally well-tolerated by people with Parkinson's disease. Studies have found it to be safer compared to other Parkinson's treatments. Nausea was the most common side effect, but overall, side effects did not differ significantly from those of a placebo. This suggests that istradefylline is safe to use, with manageable side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Parkinson's disease?

Researchers are excited about istradefylline for Parkinson's disease with cognitive impairment because it works differently from most current treatments. While standard treatments like levodopa primarily address motor symptoms by increasing dopamine levels, istradefylline targets a different pathway by blocking the adenosine A2A receptor. This unique mechanism may help alleviate both motor and cognitive symptoms by reducing neural inflammation and improving brain function. This dual action has the potential to offer more comprehensive symptom management for patients.

What evidence suggests that istradefylline might be an effective treatment for Parkinson's disease with cognitive impairment?

Research shows that istradefylline can help people with Parkinson's disease manage their symptoms. Studies have found that using istradefylline with levodopa greatly reduces the time patients experience the OFF state, when their medication isn’t working well and symptoms return. Another study found that istradefylline improves movement issues in Parkinson’s by extending the effectiveness of levodopa. In this trial, participants will receive usual care plus istradefylline to focus on improving thinking skills. These findings suggest that istradefylline positively affects Parkinson's symptoms overall. ^{1 2 4 6 7}

Who Is on the Research Team?

Matthew Barrett, MD

Principal Investigator

Virginia Commonwealth University

Are You a Good Fit for This Trial?

This trial is for individuals over 50 with Parkinson's disease who are experiencing cognitive impairment. They must be in the early to moderate stages of the disease, taking carbidopa/levodopa, and have stable medication doses. Those with dementia related to Lewy bodies, severe liver issues, or women who could become pregnant aren't eligible.

Inclusion Criteria

My Parkinson's medication has been the same for the last 4 weeks.

I am currently on carbidopa/levodopa medication.

I am over 50 years old.

Exclusion Criteria

Dementia too severe to complete study measures or to adhere to medication schedule

My liver is not working well.

I experience significant involuntary movements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive usual care and take istradefylline daily for 26 weeks

26 weeks

4 visits (in-person) at baseline, 4 weeks, 14 weeks, and 26 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Istradefylline

Trial Overview The study is testing whether a drug called Istradefylline can improve thinking and memory skills in people with Parkinson's disease who also have cognitive impairments.

How Is the Trial Designed?

Group I: Usual care plus istradefylline Experimental Treatment 1 Intervention

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

Istradefylline is already approved in United States, Japan for the following indications:

Approved in United States as Nourianz for:

• Parkinson's disease

Approved in Japan as Nouriast for:

• Parkinson's disease

Who Is Running the Clinical Trial?

Virginia Commonwealth University

Lead Sponsor

Trials

732

Recruited

22,900,000+

Kyowa Kirin, Inc.

Industry Sponsor

Trials

49

Recruited

5,700+

Published Research Related to This Trial

Istradefylline is a newly approved adjunct treatment for Parkinson's disease that helps reduce 'off' episodes when used alongside the standard levodopa/carbidopa therapy, as demonstrated in four randomized, double-blind, placebo-controlled studies.

This drug works differently than traditional Parkinson's treatments by blocking adenosine A2A receptors, and while it can be effective, it may cause side effects like dyskinesia and dizziness, and its high cost could affect accessibility for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Istradefylline: A novel agent in the treatment of "off" episodes associated with levodopa/carbidopa use in Parkinson disease. Cummins, L., Cates, ME.[2022]

Istradefylline, when used alongside levodopa, significantly reduces the time patients with Parkinson's Disease spend in the OFF state and improves motor function as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) Part III.

The study found that istradefylline is safe, with no significant differences in adverse events compared to placebo, although it was associated with a higher risk of dyskinesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Istradefylline, an adenosine A₂A receptor antagonist, for patients with Parkinson's Disease: a meta-analysis. Chen, W., Wang, H., Wei, H., et al.[2014]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT00199433

NCT00199433 | A Study of Istradefylline (KW-6002) as ... This study will compare the efficacy of 40 mg per day of istradefylline in improving the symptoms of Parkinson's disease with placebo.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7768423/

Istradefylline to Treat Patients with Parkinson's Disease ... This trial of 15 patients found that istradefylline prolonged the effective half-time of levodopa and improved cardinal parkinsonian signs, ...

3. withpower.com withpower.com/trial/istradefylline-for-parkinsons-disease-with-cognitive-impairment-a90dd

Istradefylline for Parkinson's Disease with Cognitive ... Istradefylline, when used alongside levodopa, significantly reduces the time patients with Parkinson's Disease spend in the OFF state and improves motor ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0022510X24002272

Adherence to istradefylline in patients with Parkinson's ... This descriptive study aimed to identify longitudinal istradefylline adherence patterns and to characterize factors associated with them.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9329678/

Istradefylline for OFF Episodes in Parkinson's Disease This was a phase IIb, randomized clinical trial evaluating the efficacy and safety of istradefylline at doses of 20 and 40 mg/day versus placebo ...

6. neurology.org neurology.org/doi/abs/10.1212/WNL.0000000000208502

Comparative Safety of Istradefylline in Parkinson's Disease Overall, istradefylline exhibits a favorable safety profile compared to other PD adjunct therapies, as demonstrated by both RCTs and RWE.

7. nature.com nature.com/articles/s41598-017-18339-1

The effect of istradefylline for Parkinson's disease: A meta- ... The present meta-analysis suggests that istradefylline at 40 mg/day could alleviate off time and motor symptoms derived from Parkinson's disease.