Modafinil for Freezing of Gait (FOG) in Parkinson's Disease (PD)

Study Overview
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Brief Summary
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Freezing of gait is a late stage complication of Parkinson's disease in which patients note that their feet feel stuck or glued to the ground. This can lead to imbalance and falls and the secondary complications that can result from falls such as fractures and hospitalizations. While levodopa can help freezing of gait in some patients, it does not help in all, and the dose needed to treat freezing may be limited by side effects of the medications. Currently there are no treatments targeted towards freezing of gait and the goal of this research is to see if Modafinil could be one such drug to help freezing of gait in Parkinson's disease.

Detailed Description
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Freezing of gait is a late stage complication of Parkinson's disease in which patients note that their feet feel stuck or glued to the ground. This can lead to imbalance and falls and the secondary complications that can result from falls such as fractures and hospitalizations. While levodopa can help freezing of gait in some patients, it does not help in all, and the dose needed to treat freezing may be limited by side effects of the medications. Currently there are no treatments targeted towards freezing of gait and the goal of this research is to see if Modafinil could be one such drug to help freezing of gait in Parkinson's disease. Approximately 20 subjects aged 18 or older with idiopathic Parkinson's disease with freezing of gait will be asked to enroll in the study from the patient population in the movement disorders clinic at the University of Arkansas for Medical Sciences (UAMS). Subjects will be assigned randomly 1:1 to an early start and delayed start arm of the study. In the early start arm subjects will receive 24 weeks of 50 mg oral daily Modafinil while subjects in the delayed start arm will receive 12 weeks of placebo followed by 12 weeks of 50 mg oral daily Modafinil. Assessments will be performed prior to initiation of medication at the screening visit, as well as at 12 weeks of the treatment phase. The assessments will include questionnaires to determine the frequency and severity of freezing of gait, level of mood, anxiety and apathy and quality of life, physical examination and tests of cognitive function. Objective assessment of patients walking will be conducted using a pressure sensor impregnated mat at each visit.

Official Title
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Modafinil as a Novel Therapy for the Treatment of Freezing of Gait in Parkinson's Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: modafinil 50mg
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of idiopathic PD on UK brain bank criteria. Presence of FOG based on objective assessment by the movement disorders neurologist. FOG-Q score > 8. Stable PD therapy (including medications and stimulation) for a period of 3 months prior to trial enrollment. Age ≥ 50 years. Exclusion Criteria: Patients on antidopaminergic medications for a period of less than 1 year from date of enrollment. Patients who may require adjustment of their PD medications over the 6 month period of the trial. History of allergic reactions to Modafinil or armodafinil. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, mitral valve prolapse, left ventricular hypertrophy, chronic obstructive pulmonary disease or psychiatric illness/social situations that would limit compliance with study requirements. Individuals who are pregnant or breastfeeding Non-english speaking individuals who are unable to complete the questionnaires and other assessments in English and/or follow instructions in English.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, placebo-controlled delayed start
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Early-start<br>24 weeks of modafinil 50 mg oral daily | Drug: modafinil 50mg<br>* 1 capsule oral daily<br>|
| Placebo Comparator: Delayed-start<br>12 weeks of oral placebo followed by 12 weeks of modafinil 50 mg oral daily | Drug: modafinil 50mg<br>* 1 capsule oral daily<br>Drug: Placebo oral capsule<br>* 1 capsule oral daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline Freezing of Gait (FOG) After First 12 Weeks of Treatment, as Measured by the Giladi Freezing of Gait Questionnaire (FOG-Q). | The freezing of gait questionnaire (FOG-Q) was administered by a movement disorders neurologist at baseline (week 0), and again after taking the randomly assigned treatment (either Modafinil or placebo) for 12 weeks. The FOG-Q scores 6 items between 0 and 4, for a total score of 24; higher values indicate worse FOG. | 12 weeks | 
| Mean Change From Baseline Stride Length After 12 Weeks on Treatment, as Measured Using an Instrumented Gait Mat. | Participants walked on a 20 foot instrumented gait mat for a total of 80 feet, first at baseline (week 0), and again after taking the randomly assigned treatment (either Modafinil or placebo) for 12 weeks. The stride length values usually range between 0 and 160 centimeters (the maximum stride length we have seen in an aging healthy population); lower values typically indicate more shuffling gait and have been associated with greater gait instability. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Motor Function After 12 Weeks on Treatment, as Measured by the Unified Parkinson's Disease Rating Scale Motor Score (UPDRS-III). | For each participant, the Unified Parkinson's disease Rating scale (UPDRS) was administered by a movement disorders neurologist. The scale was first administered at baseline (week 0), and again after taking the randomly assigned treatment (either Modafinil or placebo) for 12 weeks. The motor subscale of the UPDRS takes integer values between 0 and 4 for each of the 27 items for a total maximum score of 108; higher values indicate worse motor function. | 12 weeks | 
| Mean Change From Baseline Quality of Life After 12 Weeks on Treatment, as Measured by the Parkinson's Disease Questionnaire-39 (PDQ-39). | For each participant, the Parkinson's Disease Questionnaire (PDQ-39) was self-administered by participants. The questionnaire was first administered at baseline (week 0), and again after taking the randomly assigned treatment (either Modafinil or placebo) for 12 weeks. The PDQ-39 scores takes integer values between 0 and 4, for each of the 39 items for a total maximum score of 156; higher values indicate worse quality of life. | 12 weeks | 
| Mean Change From Baseline Sleep Quality After 12 Weeks on Treatment, as Measured by the REM Sleep Behavior Disorder Questionnaire (RBD-Q). | For each participant, the REM sleep behavior disorder questionnaire (RBD-Q) was self-administered by participants. The questionnaires were first administered at baseline (week 0), and again after taking the randomly assigned treatment (either Modafinil or placebo) for 12 weeks. The RBD-Q score takes integer values between 0 and 1, for each of the 13 item yes/no questions for a total maximum score of 13; higher values indicate worse sleep behavior disorder. | 12 weeks | 
| Mean Change From Baseline Sleep Quality After 12 Weeks on Treatment, as Measured by the Epworth Sleepiness Scale (ESS). | For each participant, the Epworth Sleepiness Scale (ESS) questionnaires was self-administered by participants. The questionnaires were first administered at baseline (week 0), and again after taking the randomly assigned treatment (either Modafinil or placebo) for 12 weeks. The ESS takes integer values between 0 and 3, for each of the 8 items for a total maximum score of 24; higher values indicate more daytime sleepiness. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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freezing of gait