The Effect of Rasagiline on Cognition in Parkinson's Disease

While Parkinson's disease has historically been defined in terms of its motor symptomatology, studies have shown that non-motor deficits form an important part of the syndrome. Cognitive deficits can occur even in the early stages of Parkinson's disease. These deficits are often subtle and do not rise to the level of impairment necessary for a diagnosis of dementia; however these deficits are discernable with neuropsychological testing and may produce subjective complaints of cognitive decline and mild functional difficulties in some patients. The traditional pharmacological interventions for Parkinson's disease have focused on controlling and alleviating motor symptoms with levodopa and dopamine agonists. However, these medications treat the symptoms of PD, but do not alter the course or progression of the underlying disorder. In contrast, rasagiline, an MAO-B inhibitor, has recently shown benefits consistent with a possible disease-modifying effect. Given the positive and intriguing findings seen with treatment with rasagiline, the investigators propose to study the effects of this medication on cognition in patients with mild to moderate stage Parkinson's disease.

Hypotheses:

1. Rasagiline will improve cognitive function, as measured by performance on neuropsychological tests in PD patients who do not suffer from dementia.
2. Rasagiline will not negatively affect neuropsychiatric functioning.

Study Overview

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

Detailed Description

The results of our study found that while participants receiving rasagiline showed some improvements in their motor symptoms, as measured by the UPDRS, no significant changes were found on any of the neuropsychological measures after six months of treatment with rasagiline. Further, the participant group who received placebo also did not show significant change on any of the neuropsychological measures over the six month course of our study. Finally, the cognitive performance of our treatment and placebo groups did not differ significantly from one another at baseline or after six months of study participation.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Butler Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age 40 or older
• able to speak and read English, at least 6 years of formal education
• a diagnosis of PD
• have a family member or caregiver willing to fill out study questionnaires
• Participants will have been on stable medication regimens (no new PD medications and no changes to existing PD medication dosages) for the 4 weeks prior to study enrollment.
• If participants are already taking other Parkinson's medications at time of study enrollment, the dosages of these medications must remain stable throughout study participation.
• Changes to existing Parkinson's disease medications dosages or addition of other medications to treat Parkinson's disease after study enrollment will result in removal from study.
• Participants are allowed to begin non-PD medications or to have changes to their existing non-PD medications if these additions and changes are deemed medically necessary.

Exclusion Criteria:

• currently taking any MAO inhibitor
• currently taking a cognition-enhancing medication such as a cholinesterase inhibitor medication or memantine
• dementia (Mini-Mental Status Exam score below 21/30), significant depression (Beck Depression Inventory- Short Form score >7)
• presence of a another neurodegenerative disorder besides PD
• unstable cardiac disorder, clinically significant hepatic
• lung or renal disease
• In addition, changes to dosages of PD-related medications or the addition of other PD medications during the 6 month study enrollment will result in dismissal from the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rasagiline; Participants in this arm will receive 1 mg of rasagiline daily for the six month duration of the study.	Drug: Rasagiline; 1 mg daily; Other Names: Azilect
Placebo Comparator: Placebo; Participants in this group will receive 1 mg of placebo daily for the six month duration of the study.	Drug: Placebo; 1 mg daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rey Auditory Verbal Learning Test	This is a 15 item supraspan verbal memory test. This measure assesses immediate memory span, new learning, susceptibility to interference, retention, and recognition memory.	Change in score from day 1 of study enrollment and score after 6 months of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Controlled Oral Word Association Test	This test evaluates the spontaneous production of words beginning with a given letter of the alphabet under timed conditions. It is used to assess executive functioning.	day 1 of study enrollment and after 6 months of treatment
Animal Fluency	Participants are asked to produce as many animal names as they can in one minute. This measure assesses executive functioning.	day 1 of study enrollment and after 6 months of treatment
Judgement of Line Orientation from the Repeat Battery for the Assessment of Neuropsychological Status	This measure assesses spatial perception and orientation without requiring a motor output.	day 1 of study enrollment and after 6 months of treatment
Digit Span from the Wechsler Adult Intelligence Scale- Fourth Edition	This is a measure of attention and working memory which requires participants to repeat a series of digits forward, in reverse, and to sequence a series of digits.	day 1 of study enrollment and after 6 months of treatment
Trail Making Test	These are tests of speed for attention, sequencing, mental flexibility, and visual search.	day 1 of study enrollment and after 6 months of treatment
Digit Symbol Modalities Test	This test assesses cognitive processing speed, and visuomotor coordination and is one of the most sensitive measures of cognitive dysfunction available.	day 1 of study enrollment and after 6 months of treatment
Parkinson's Disease Quality of Life Questionnaire	The 39-item Parkinson's disease questionnaire (PDQ-39) is one of the most often used instruments to measure treat¬ment effect on quality of life in PD.	day 1 of study enrollment and after 6 months of treatment

Collaborators and Investigators

• Sponsor: Brown University
• Collaborators: Teva Pharmaceuticals USA
• Investigators: Principal Investigator: Laura L. Frakey, Ph.D., Brown University; Principal Investigator: Joseph Friedman, MD, Brown University

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: June 23, 2011
• First Submitted That Met QC Criteria: June 24, 2011
• First Posted (Estimate): June 27, 2011

Study Record Updates

• Last Update Posted (Estimate): February 5, 2015
• Last Update Submitted That Met QC Criteria: February 3, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Keywords: cognition; Parkinson's disease; executive function; rasagiline
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; 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: TNSAZL0016