Effect of Istradefylline Treatment on Behavioral Measures of Apathy in Parkinson's Disease.

Parkinson Disease Clinical Trial

Official title:

Effect of Istradefylline Treatment on Behavioral Measures of Apathy in Parkinson's Disease.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05182151
• Other study ID #: Pro00108116
• Status: Terminated
• Start date: July 29, 2022
• Est. completion date: December 1, 2023

Study information

• Verified date: January 2024
• Source: Medical University of South Carolina
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Apathy is defined as a lack of feeling, emotion, interest, or concern. Apathy also involves reduction or loss of motivation and goal-directed behavior. Clinically significant apathy, where meaningful activities are given up and quality of life is diminished, is common in people with Parkinson's disease (PD).

Many individuals with Parkinson's disease experiencing fluctuations in the severity of their movement problems and medication "off" time. "Off" time refers to periods of the day between doses of PD medication when your motor symptoms (e.g., tremor, stiffness, slowness, walking problems, etc.) are worse and interfere with your ability to complete tasks of daily living. The investigational drug, Istradefylline, is an FDA-approved medication to treat motor fluctuations and "off" time in PD.

The purpose of this study is to investigate whether people with Parkinson's disease (PD) who are treated with istradefylline (ISD) show improvements in motivation and apathy over a 12-week period. Specifically, we wish to see whether people with PD who are treated with ISD engage in more physical and recreational activities, such as hobbies and other interests.

Description:

Apathy is a clinical syndrome characterized by lack of motivation, interest, engagement, and emotional reactivity for goal-directed behaviors (Starkstein et al., 2008). A common and troublesome symptom in Parkinson's disease (PD), apathy is associated with diminished quality of life for both the patient and care partner (Van Reekum, Stuss, & Ostrander, 2005; Barone et al., 2009). To the extent that apathy reduces engagement in physical and social activities, it may also result in more rapid disease progression and cognitive decline (e.g., Crotty & Schwarzchild, 2020). Addressing apathy is therefore a crucial component of treating PD. A recent open-label study demonstrated significant reduction in self-reported apathy with Istradefylline (ISD) in PD (Nagayama et al, 2019). This unsurprising result likely reflects contributions from known benefits of ISD with respect to daytime somnolence and improved motor functioning (Matsuura et al., 2017; Suzuki et al. 2017), as well as enhanced functioning of dopamine-mediated reward pathways. However, patients with PD advanced enough to warrant treatment with ISD may also have diminished insight and awareness, and therefore not be particularly reliable reporters (e.g., Orfei et al., 2018). It is also unknown whether and to what extent this is correlated with actual changes in behavior and caregiver burden.

The objective of this study is to determine whether treatment with ISD increases engagement in physical and other meaningful activities in patients with Parkinson's disease.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: December 1, 2023
• Est. primary completion date: December 1, 2023
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

1. Diagnosis of PD consistent with United Kingdom Brain Bank Criteria or the Movement Disorder Society Research Criteria for the Diagnosis of Parkinson's Disease, with bradykinesia and sequence effect being present, and prominent motor asymmetry (if no rest tremor).

2. Current treatment with levodopa.

3. Stable on levodopa and other study-approved medications for PD motor symptoms for at least four weeks prior to screening.

4. Clinically significant wearing-off / fluctuating symptomatology warranting treatment with ISD

5. Presence of apathy at baseline (LARS > -22)

6. Living with adult informant

Exclusion Criteria:

Current or prior treatment with istradefylline. 2. History of Deep Brain Stimulation (DBS) surgery, ablative surgery (e.g., pallidotomy, thalamotomy, focused ultrasound, etc.), Duopa pump implantation, or other invasive intervention for Parkinson's disease symptoms. 3. Injury or concomitant health condition at screening that would preclude engagement in light physical activity. 10 4. Prior history of cerebrovascular accident (e.g., stroke or aneurysm) or seizure disorder (other than febrile seizures during childhood). 5. Dementia (MoCA<22) 6. Psychotic symptoms that would raise concern for safe use of ISD, as indicated by domains A (delusions) and B (hallucinations) of the Neuropsychiatric Inventory (NPI), and defined as a score of =4 on either the A (frequency × severity) or B (frequency × severity) scales of the NPI. 7. Depressive mood symptoms at baseline likely to interfere with response to treatment (BDI-II>19) 8. Active suicidal ideation within 1 year prior to Screening Visit as determined by a positive response to Question 4 or 5 on the C-SSRS. 9. Diagnosis or treatment for any central nervous system disorder other than Parkinson's disease that could be expected in the eyes of the investigator to impact ability to participate in study. 10. Contraindications / conditions that would preclude safe dosing of 40mg ISD 11. Change in medications for mood or anxiety within 6 weeks of enrollment or anticipation of change in medications for mood or anxiety during the 8-week study period.

12. Moderate or severe hepatic impairment. 13. Current treatment with strong CYP3A4 inhibitors 14. Current treatment with strong CYP3A4 inducers 15. Pregnant women are not able to participate due to unknown safety risks associated with ISD

Related Conditions & MeSH terms

• Apathy
• Parkinson Disease

Intervention

Drug:
• Istradefylline 40 mg
adenosine A2A receptor antagonist

Locations

Country	Name	City	State
United States	MUSC Movement Disorders Program	Charleston	South Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Medical University of South Carolina	Kyowa Kirin, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Physical Activity Scale for the Elderly (PASE)	telephone survey	12 weeks
Secondary	Engagement in Meaningful Activities Survey (EMAS)	telephone survey	12 weeks
Secondary	Lille Apathy Rating Scale (LARS)	apathy scale	12 weeks
Secondary	Apathy Evaluation Scale (AES)	patient and informant	12 weeks
Secondary	Beck Depression Inventory (BDI-2)	Depression scale	12 weeks
Secondary	Epworth Sleepiness Scale (ESS)	scale to assess sleepiness	12 weeks
Secondary	Global Impression of Change	patient and informant	12 weeks
Secondary	Unified Parkinson's Disease Rating Scale	motor symptom rating	12 weeks