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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT01168596
First received: February 19, 2010
Last updated: December 10, 2013
Last verified: September 2012
  Purpose

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


Condition Intervention Phase
Parkinson's Disease
Drug: Rasagiline
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Rasagiline for the Symptomatic Treatment of Fatigue in Parkinson's Disease: A Bi-Center, Placebo-Controlled Study (The REST Fatigue Trial)

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Modified Fatigue Impact Scale (MFIS) [ Time Frame: Change from baseline to week 12 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Fatigue Severity Scale (FSS) [ Time Frame: Change from baseline to week 12 ] [ Designated as safety issue: No ]
    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.

  • Multidimensional Fatigue Inventory (MFIS) [ Time Frame: Change from baseline to week 12 ] [ Designated as safety issue: No ]
    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.

  • PD Quality of Life Scale (PDQ39) [ Time Frame: Change from baseline to week 12 ] [ Designated as safety issue: No ]
    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.

  • Paced Auditory Serial Addition Test (PASAT) [ Time Frame: Change from baseline to week 12 ] [ Designated as safety issue: No ]
    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.

  • Finger Tapping [ Time Frame: Change from baseline to week 12 ] [ Designated as safety issue: No ]
    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.

  • Hand-grip Strength [ Time Frame: Change from baseline to week 12 ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Parkinson's Disease Sleep Scale (PDSS) [ Time Frame: Change from baseline to week 12 ] [ Designated as safety issue: No ]
    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.

  • Marin Apathy Inventory (Apathy Evaluation Scale) [ Time Frame: Change from baseline to week 12 ] [ Designated as safety issue: No ]
    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.

  • Visual Analog Scale - Subset: Afraid [ Time Frame: Change from baseline to week 12 ] [ Designated as safety issue: No ]
    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).

  • State-Trait Anxiety Inventory (STAI) [ Time Frame: Change from baseline to week 12 ] [ Designated as safety issue: No ]
    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.

  • Becks Depression Inventory (BDI-II) [ Time Frame: Change from baseline to week 12 ] [ Designated as safety issue: No ]
    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.

  • Unified Parkinson's Disease Rating Scale - Motor (UPDRS Part III) [ Time Frame: Change from baseline to week 12 ] [ Designated as safety issue: No ]
    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.

  • Visual Analog Scale - Subset: Confused [ Time Frame: Change from baseline to week 12 ] [ Designated as safety issue: No ]
    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).

  • Visual Analog Scale - Subset: Sad [ Time Frame: Change from baseline to week 12 ] [ Designated as safety issue: No ]
    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).

  • Visual Analog Scale - Subset: Angry [ Time Frame: Change from baseline to week 12 ] [ Designated as safety issue: No ]
    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).

  • Visual Analog Scale - Subset: Energetic [ Time Frame: Change from baseline to week 12 ] [ Designated as safety issue: No ]
    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).

  • Visual Analog Scale - Subset: Tired [ Time Frame: Change from baseline to week 12 ] [ Designated as safety issue: No ]
    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).

  • Visual Analog Scale - Subset: Happy [ Time Frame: Change from baseline to week 12 ] [ Designated as safety issue: No ]
    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).

  • Visual Analog Scale - Subset: Tense [ Time Frame: Change from baseline to week 12 ] [ Designated as safety issue: No ]
    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).


Enrollment: 30
Study Start Date: December 2009
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Azilect

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.

  Eligibility

Ages Eligible for Study:   40 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01168596

Locations
United States, Colorado
University of Colorado Anschutz outpatient Pavilion
Aurora, Colorado, United States, 80045
United States, Florida
Shands and University of Florida Medical Plaza
Gainesville, Florida, United States, 32610
United States, Ohio
Cleveland Clinic Center for Neurological Restoration
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
University of Florida
Investigators
Principal Investigator: Irene A Malaty, MD University of Florida Department of Neurology
  More Information

No publications provided

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT01168596     History of Changes
Other Study ID Numbers: 20091035
Study First Received: February 19, 2010
Results First Received: June 14, 2013
Last Updated: December 10, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Florida:
Parkinson's Disease
Fatigue

Additional relevant MeSH terms:
Parkinson Disease
Fatigue
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Signs and Symptoms
Rasagiline
Monoamine Oxidase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014