Rasagiline for the Symptomatic Treatment of Fatigue in Parkinson's Disease

Study Overview
=================
Brief Summary
-----------------
The purpose of the research study is to determine if rasagiline is an effective treatment for fatigue in patients with Parkinson's disease (PD).

Detailed Description
-----------------
Despite the fact that fatigue affects 40-50% of all patients with PD and is a leading cause of disability, we currently do not have any effective treatments for this symptom. Rasagiline is a well-tolerated and effective treatment for the motor symptoms of PD. Rasagiline is a MAO-B inhibitor that may decrease the breakdown of dopamine. Many patients report an improvement in their energy levels when on this medication. A proven treatment for PD fatigue would significantly improve the quality of life for numerous patients and their caregivers.

Official Title
-----------------
Rasagiline for the Symptomatic Treatment of Fatigue in Parkinson's Disease: A Bi-Center, Placebo-Controlled Study (The REST Fatigue Trial)

Conditions
-----------------
Parkinson's Disease

Intervention / Treatment
-----------------
* Drug: Rasagiline
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: A clinical diagnosis of idiopathic PD by a movement disorders specialist. All subjects will be diagnosed using the UK Brain Bank criteria (Hughes et al., 1992). Age between 40-85 years. Able to sign and understand informed consent; and cognitively able to carry out the procedures in the study Stable on all PD medications for at least 30 days; and psychotropic medications for at least 90 days. Treatment naïve subjects who are appropriate candidates to begin MAO-inhibitor monotherapy as treatment for their PD may also be included in this study. Fatigue Severity Scale ≥ 36 (KRupps et al., 1989) Exclusion Criteria: Clinically significant medical disease that is associated independently with fatigue (e.g. significant cardiac or pulmonary disease, anemia, obstructive sleep apnea, liver or kidney failure). History of neurological illnesses other than PD or a history of a significant head trauma (involving unconsciousness). Evidence of secondary or atypical parkinsonism as suggested by the presence of any of the following: 1) history of stroke(s), 2) exposure to toxins or neuroleptics, 3) history of encephalitis, 4) neurological signs of upper motor neuron disease, cerebellar involvement, supranuclear gaze palsy, or significant orthostatic hypotension. MRI or CT scan with significant evidence of brain atrophy or other abnormalities (e.g. lacunar infarcts or iron deposits in the putamen. Clinical diagnoses of dementia; or an MMSE score of < 25. Unstable, newly diagnosed, or newly treated (i.e. less than 3 months) major psychiatric disorder such as depression or anxiety Beck's Depression Inventory score >14. Current or prior placement of Deep Brain Stimulator. Currently taking an MAO-B inhibitor or medications which are used as fatigue treatments, including amantadine, modafinil, methylphenidate, atomoxetine or other psychostimulants. Previously taken an MAO-B inhibitor for more than 2 weeks. Hypersensitivity to rasagiline or its products On mirtazapine, venlafaxine, regular use of compounds with vasoconstrictors, tramadol, meperidine, propoxyphene, dextromethorphan, St. John's wort, cyclobenzaprine On omeprazole, ciprofloxacin or drugs that are metabolized through CYP1A2

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: sugar pill<br>Placebo tablet, 1 per day, duration is approximately 12 weeks. | Drug: Placebo<br>* Comparison of Rasagiline versus placebo. Placebo tablet, 1 per day, duration is approximately 12 weeks.<br>|
| Active Comparator: rasagiline<br>Rasagiline tablet, 1 mg, 1 per day, duration is approximately 12 weeks. | Drug: Rasagiline<br>* Comparison of Rasagiline versus placebo. Rasagiline tablet, 1 mg, 1 per day, duration is approximately 12 weeks.<br>* Other names: Azilect;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Fatigue Impact Scale (MFIS) | The MFIS rates how much of a problem fatigue has caused the subjects during the past month, including the day of testing. It consists of 21 questions of fatigue on quality of life. Each subject is asked to circle the appropriate response for each item: 0=never, 1=rarely, 2=sometimes, 3=often, 4=always, 5=almost always. The minimum score is 0 and the maximum is 105. The higher the score, the more fatigue the subject. | Change from baseline to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fatigue Severity Scale (FSS) | The Fatigue Severity Score consists of a nine-item questionnaire to identify common features of fatigue. Patients are instructed to choose a number from 1 to 7 that indicates their degree of agreement with each statement, where 1 = strongly disagree and 7 = strongly agree. Scores can range from a minimum of 9 to a maximum of 63. The higher the score, the more fatigue the subject. | Change from baseline to week 12 | 
| Multidimensional Fatigue Inventory (MFIS) | The Multidimensional Fatigue Inventory (MFIS) is a 20-item self-report instrument designed to measure fatigue. It covers the following dimensions: general fatigue, physical fatigue, mental fatigue, reduced motivation and reduced activity. Subjects are instructed to choose a number from 1 to 5 that indicates their degree of agreement with each statement where 1 indicates that it is true and 5 that it is not true. There are positive and negative statements in the questionnaire. The range is 1 to 100, the higher the number the higher the fatigue. | Change from baseline to week 12 | 
| PD Quality of Life Scale (PDQ39) | PD Quality of Life Scale (PDQ39) is a 39-item questionnaire, which measures eight dimensions of health (mobility, activities of daily living, emotional well-being, stigma, social support, cognitions, communication and bodily discomfort) over the past 30 days. Dimension scores are coded on a scale of 0 (never) to 5 (always). The higher the score, the worse the quality of life affected by PD. The range for this test is 0 to 195. All eight dimensions are added for a total score. | Change from baseline to week 12 | 
| Paced Auditory Serial Addition Test (PASAT) | The Paced Auditory Serial Addition Test (PASAT) is a neuropsychological test used to assess capacity and rate of information processing and sustained and divided attention. Where subjects are given a number (every 3 seconds for the first series and 2 seconds for the second series) and are asked to add the number they just heard with the number they heard before. This is a challenging task that involves working memory, attention, and arithmetic capabilities. | Change from baseline to week 12 | 
| Finger Tapping | The patient is asked to use the index finger on the side most affected by Parkinson's disease to tap for sixty seconds with the number of taps at 30 seconds and 60 seconds recorded. | Change from baseline to week 12 | 
| Hand-grip Strength | The patients use the hand on the side most affected by Parkinson's disease to grip the dynamometer with as much strength as they can for 3 consecutive tries. The highest score will be their maximal voluntary contraction (MVC). The subject then rests for 60 seconds. The subject is asked to try to maintain 70% of their MVC and the duration the subject is able to maintain above 50% of their MVC is recorded. Immediately after the maintenance test, the subject performs three more MVCs and each one is recorded. These results are the duration the subject is able to maintain above 50% of their MVC. | Change from baseline to week 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Parkinson's Disease, Fatigue