Istradefylline Effect Protocol on Parkinson's Disease Tremor

Georgetown University

Status and phase: Completed; Phase 4

Conditions: Tremor; Parkinson Disease

Treatments: Drug: Istradefylline Pill

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05885360

STUDY00005472

Details and patient eligibility

About

This is an investigator-initiated trial. In this 6-month open label, single arm, exploratory pilot study, the investigator intends to enroll a pilot sample of 25 patients with Parkinson's disease who are being started on the novel FDA approved medication "Istradefylline'' as an add on therapy for management of their motor symptoms (based on the judgment of the movement disorders specialist, if patients are in sub-optimal management of their symptoms on maximum tolerable dose of their dopaminergic medications). The investigator will evaluate their motor symptoms before starting the new medication, including their MDS-UPDRS total and MDS-UPDRS-III scores.

Full description

In this 6-month open label, single arm, exploratory pilot study, the investigator intends to enroll a pilot sample of 25 patients with Parkinson's disease who are being started on the novel FDA approved medication "Istradefylline'' as an add on therapy for management of their motor symptoms (based on the judgment of the movement disorders specialist, if patients are in suboptimal management of their symptoms on maximum tolerable dose of their dopaminergic medications). The investigator will evaluate their motor symptoms before starting the new medication, including their MDS-UPDRS total and MDS-UPDRS-III scores.

Based on data from an early experience limited data set within our clinical practice of patients taking Istradefylline, the investigator noted improvement in motor symptoms on PDRS-III. The investigator evaluated the degree of tremor with a tremor quantifying software before and after 8 weeks of therapy. Tremor amplitude, frequency and severity improved in the first two patients based on said parameters.

Secondary analysis in week 24 will include all aforementioned assessments. The investigator will compare their score and results before and after the medication.

The therapeutic intervention will consist of evaluating the effect of the addition of Istradefylline 40 mg daily (after two weeks of Istradefylline 20 mg daily) in patients already on levodopa and other anti- parkinsonian treatments. Patients will be screened based on inclusion and exclusion criteria. Enrolled patients will need to be on a stable regimen of all their concomitant medications for at least 30 days prior to baseline visit. All PD concomitant medications are allowable. Participants must also have a MOCA (Montreal Cognitive Assessment) of 22 or greater, and the absence of a diagnosis of dementia.

Tremor score will be clinically defined by the presence of a sum score of at least 8 of 32 of the MDS-UPDRS tremor items 16, 20, and 21 (referred to as tremor score). The generation of this sum score is based on the validity of the MDS-UPDRS regarding tremor, 19 and the clinical experience, that the MDS-UPDRS tremor items reflect different but similarly important aspects of Parkinsonian tremor, including the impairment of activities of daily living by tremor.

Enrollment: 27 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• · Written informed consent

  • Capable of providing informed consent and complying with study procedures
  • Clinical diagnosis of Parkinson's disease according to the United Kingdom Brain Bank criteria which includes the following.
  • Bradykinesia
  • At least one of the following:
  • Muscular righty
  • 4-6 Hz rest tremor
  • Postural instability not caused by primary visual, vestibular, cerebellar, or proprioceptive dysfunction
  • Must be on a stable regimen of all current concomitant medication, including carbidopa-levodopa for at least 30 days prior to baseline visit
  • Participants also have a MOCA (Montreal Cognitive Assessment) score of 22 or greater
  • Study subjects are willing to present for all study visits and take medication.
  • The MDS-UPDRS I-III will be used to assess a baseline tremor score

Exclusion criteria

• · Diagnosis of dementia - defined by NIH as the loss of cognitive functioning such as thinking, remembering, and reasoning, to such an extent that it interferes with a person's daily life and activities.

  • Parkinson's plus syndromes or any other disorder other than idiopathic Parkinson's disease
  • Moderate to severe dyskinesia is defined as:
  • Moderate: Dyskinesias impact on activity to the point that the patient usually does not perform some activities or does not usually participate in some social activities during dyskinetic episodes
  • Severe: Dyskinesia impacts activities to the point that the patient usually does not perform most activities or participate in most social activities during dyskinetic episodes
  • Patients with severe cardiac disease or congestive heart failure
  • Severe uncontrolled orthostatic hypotension
  • Psychosis or psychotic symptoms that would raise concern for safe use of IST, 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 x severity) or B (frequency x severity) scales of the NPI
  • Active neoplastic disorder
  • Current treatment with strong CYP3A4 inhibitors
  • Current treatment with strong CYP3A4 inducers

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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27 participants in 1 patient group

Istradefylline 20 and 40 mg

Experimental group

Description:

The study intervention will be to add 20 mg Istradefylline for 2 weeks, following which the dose will be increased to 40 mg daily for the remainder of the 24 weeks.

Treatment:

Drug: Istradefylline Pill