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

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

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

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: Placebo; Drug: Rasagiline

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz outpatient Pavilion
  • Florida
    • Gainesville, Florida, United States, 32610
      • Shands and University of Florida Medical Plaza
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Center for Neurological Restoration

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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).
2. Age between 40-85 years.
3. Able to sign and understand informed consent; and cognitively able to carry out the procedures in the study
4. Stable on all PD medications for at least 30 days; and psychotropic medications for at least 90 days.
5. Treatment naïve subjects who are appropriate candidates to begin MAO-inhibitor monotherapy as treatment for their PD may also be included in this study.
6. Fatigue Severity Scale ≥ 36 (KRupps et al., 1989)

Exclusion Criteria:

1. 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).
2. History of neurological illnesses other than PD or a history of a significant head trauma (involving unconsciousness).
3. 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.
4. MRI or CT scan with significant evidence of brain atrophy or other abnormalities (e.g. lacunar infarcts or iron deposits in the putamen.
5. Clinical diagnoses of dementia; or an MMSE score of < 25.
6. Unstable, newly diagnosed, or newly treated (i.e. less than 3 months) major psychiatric disorder such as depression or anxiety
7. Beck's Depression Inventory score >14.
8. Current or prior placement of Deep Brain Stimulator.
9. Currently taking an MAO-B inhibitor or medications which are used as fatigue treatments, including amantadine, modafinil, methylphenidate, atomoxetine or other psychostimulants.
10. Previously taken an MAO-B inhibitor for more than 2 weeks.
11. Hypersensitivity to rasagiline or its products
12. On mirtazapine, venlafaxine, regular use of compounds with vasoconstrictors, tramadol, meperidine, propoxyphene, dextromethorphan, St. John's wort, cyclobenzaprine
13. On omeprazole, ciprofloxacin or drugs that are metabolized through CYP1A2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: sugar pill; Placebo tablet, 1 per day, duration is approximately 12 weeks.	Drug: Placebo; Comparison of Rasagiline versus placebo. Placebo tablet, 1 per day, duration is approximately 12 weeks.
Active Comparator: rasagiline; Rasagiline tablet, 1 mg, 1 per day, duration is approximately 12 weeks.	Drug: Rasagiline; Comparison of Rasagiline versus placebo. Rasagiline tablet, 1 mg, 1 per day, duration is approximately 12 weeks.; 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parkinson's Disease Sleep Scale (PDSS)	The Parkinson's disease sleep scale (PDSS) is a 15-item visual analogue scale that assesses the profile of nocturnal disturbances in Parkinson's disease patients. The severity of symptoms of sleep over the past week is marked with a cross along a 10 cm line (labeled worst to best state). Responses are quantified by measuring the distance along each line to the intersection with the cross in centimetres, to the nearest 0.1 cm. The scores for each item range from 0 (symptom severe and always experienced) to 10 (symptom-free). The maximum score for PDSS is 150.	Change from baseline to week 12
Marin Apathy Inventory (Apathy Evaluation Scale)	The Marin Apathy Inventory (Apathy Evaluation Scale) is a 14-item inventory measuring apathy of the subject over the past 2 to 4 weeks. Subjects are instructed to choose an answer from 0 to 3: 0=not at all, 1 = slightly, 2 = some, 3 = a lot, to questions related to apathy. The range would be 0 to 42, the higher the score the worse the apathy.	Change from baseline to week 12
Visual Analog Scale - Subset: Afraid	The Visual Analog Scale is a measurement instrument for subjective characteristics or attitudes that cannot be directly measured. The severity of attitude at the time of testing is marked with a cross along a 10 cm line (labeled neutral to afraid, confused, sad, angry, energetic, tired, happy or tense). Responses are quantified by measuring the distance along each line to the intersection with the cross in centimetres, to the nearest 0.1 cm. The scores for each item range from 0 (symptoms-free) to 10 (symptom severe).	Change from baseline to week 12
State-Trait Anxiety Inventory (STAI)	The State-Trait Anxiety Inventory (STAI) is 40-item psychological inventory based on a 4-point Likert scale. Higher scores are positively correlated with higher levels of anxiety. The range for this test is 0 to 160.	Change from baseline to week 12
Becks Depression Inventory (BDI-II)	The Becks Depression Inventory (BDI-II) is a 21-question inventory measuring the severity of depression. Each subject is instructed to choose an answer on a scale value of 0 to 3 with the total score from 0 to 63. Higher total scores indicate more severe depressive symptoms.	Change from baseline to week 12
Unified Parkinson's Disease Rating Scale - Motor (UPDRS Part III)	Unified Parkinson's Disease Rating Scale - Motor (UPDRS Part III)is a 14-question inventory measuring the motor functions of patients with Parkinson's Disease. Each subject is rated on a scale of 0 to 4 with the total score from 0 to 56. Higher total scores indicate more impairment of motor function.	Change from baseline to week 12
Visual Analog Scale - Subset: Confused	The Visual Analog Scale is a measurement instrument for subjective characteristics or attitudes that cannot be directly measured. The severity of attitude at the time of testing is marked with a cross along a 10 cm line (labeled neutral to afraid, confused, sad, angry, energetic, tired, happy or tense). Responses are quantified by measuring the distance along each line to the intersection with the cross in centimetres, to the nearest 0.1 cm. The scores for each item range from 0 (symptoms-free) to 10 (symptom severe).	Change from baseline to week 12
Visual Analog Scale - Subset: Sad	The Visual Analog Scale is a measurement instrument for subjective characteristics or attitudes that cannot be directly measured. The severity of attitude at the time of testing is marked with a cross along a 10 cm line (labeled neutral to afraid, confused, sad, angry, energetic, tired, happy or tense). Responses are quantified by measuring the distance along each line to the intersection with the cross in centimetres, to the nearest 0.1 cm. The scores for each item range from 0 (symptoms-free) to 10 (symptom severe).	Change from baseline to week 12
Visual Analog Scale - Subset: Angry	The Visual Analog Scale is a measurement instrument for subjective characteristics or attitudes that cannot be directly measured. The severity of attitude at the time of testing is marked with a cross along a 10 cm line (labeled neutral to afraid, confused, sad, angry, energetic, tired, happy or tense). Responses are quantified by measuring the distance along each line to the intersection with the cross in centimetres, to the nearest 0.1 cm. The scores for each item range from 0 (symptoms-free) to 10 (symptom severe).	Change from baseline to week 12
Visual Analog Scale - Subset: Energetic	The Visual Analog Scale is a measurement instrument for subjective characteristics or attitudes that cannot be directly measured. The severity of attitude at the time of testing is marked with a cross along a 10 cm line (labeled neutral to afraid, confused, sad, angry, energetic, tired, happy or tense). Responses are quantified by measuring the distance along each line to the intersection with the cross in centimetres, to the nearest 0.1 cm. The scores for each item range from 0 (symptoms-free) to 10 (symptom severe).	Change from baseline to week 12
Visual Analog Scale - Subset: Tired	The Visual Analog Scale is a measurement instrument for subjective characteristics or attitudes that cannot be directly measured. The severity of attitude at the time of testing is marked with a cross along a 10 cm line (labeled neutral to afraid, confused, sad, angry, energetic, tired, happy or tense). Responses are quantified by measuring the distance along each line to the intersection with the cross in centimetres, to the nearest 0.1 cm. The scores for each item range from 0 (symptoms-free) to 10 (symptom severe).	Change from baseline to week 12
Visual Analog Scale - Subset: Happy	The Visual Analog Scale is a measurement instrument for subjective characteristics or attitudes that cannot be directly measured. The severity of attitude at the time of testing is marked with a cross along a 10 cm line (labeled neutral to afraid, confused, sad, angry, energetic, tired, happy or tense). Responses are quantified by measuring the distance along each line to the intersection with the cross in centimetres, to the nearest 0.1 cm. The scores for each item range from 0 (symptoms-free) to 10 (symptom severe).	Change from baseline to week 12
Visual Analog Scale - Subset: Tense	The Visual Analog Scale is a measurement instrument for subjective characteristics or attitudes that cannot be directly measured. The severity of attitude at the time of testing is marked with a cross along a 10 cm line (labeled neutral to afraid, confused, sad, angry, energetic, tired, happy or tense). Responses are quantified by measuring the distance along each line to the intersection with the cross in centimetres, to the nearest 0.1 cm. The scores for each item range from 0 (symptoms-free) to 10 (symptom severe).	Change from baseline to week 12

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Irene A Malaty, MD, University of Florida Department of Neurology

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: February 19, 2010
• First Submitted That Met QC Criteria: July 22, 2010
• First Posted (Estimate): July 23, 2010

Study Record Updates

• Last Update Posted (Estimate): January 10, 2014
• Last Update Submitted That Met QC Criteria: December 10, 2013
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: Fatigue; Parkinson's Disease
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Fatigue; Parkinson Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Neuroprotective Agents; Protective Agents; Monoamine Oxidase Inhibitors; Rasagiline
• Other Study ID Numbers: 20091035