Effect of Rasagiline on Balance in Parkinson's Disease as Measured by Computerized Posturography
Phase: PHASE4
Conditions: PARKINSON DISEASE (Disorder)
Sponsor: New York Medical College

 
 
 
 
 
 
 
 
 
 
Effect of rasagiline on balance in Parkinson’s disease as 
measured by computerized posturography 
 
Fekete Robert 
 
Approved: 9/15/2014 
 
Department of Neurology 
New York Medical College, Valhalla, NY 
United States of America 
 
Corresponding Author 
Dr. Robert Fekete 
19 Bradhurst Ave 
Hawthorne, NY 10532 
United States of America 
Phone: 914-345-1313 
Fax: 914-345-5004 
Email: robertfekete@hotmail.com 
 
 
Keywords: rasagiline, balance, posturography, Parkinson’s disease 

Abstract: 
 
Background: 
 
Falls occur in a majority of Parkinson’s disease (PD) patients. Balance disturbance can be 
measured by computer dynamic posturography. The effect of monoamine oxidase 
inhibition on PD patients as measured by computer dynamic posturography has not been 
previously studies.  
 
Methods: 
 
The study will test the hypothesis that therapy with rasagiline improves balance in PD 
patients as measured by computerized dynamic posturography. 5 subjects will be 
randomized to rasagiline or placebo and 5 further subjects will be randomized to 
rasagiline as adjuvant therapy versus placebo. Subjects will be analyzed by computerized 
dynamic posturography testing. The device measures body sway under varying visual and 
vestibular cues and is used for assessment of balance. Subjects will be evaluated at 
baseline prior to taking first tablet as well as at 4 weeks and 8 weeks. In the adjuvant 
therapy arm, subjects will be evaluated on rasagiline but in a functional OFF state for 
their other PD medications. If the scores are normally distributed, we will determine 
whether data variance is approximately equal in all tested groups. If these conditions are 
met, data evaluation will continue using repeated measures ANOVA with between factor 
of drug (levels: rasagiline, placebo) and within factor of treatment (levels: before, after). 
Level of significance will be preset to 0.05. 
 
 

Background: 
Posturography testing for Parkinson’s disease patients on monoamine oxidase (MAO) 
inhibitors in general has not been studied previously. In Wood’s study of patients with 
Parkinson’s disease, falls occurred in 68.3% of the subjects [1]. In Ebmeier’s population 
study of idiopathic Parkinson’s disease patients, signs of postural instability on clinical 
examination were among the factors listed in premature death [2].  
 
Hypothesis 
 
The hypothesis is that therapy with rasagiline improves balance in PD patients as 
measured by computerized dynamic posturography.  
 
 
Methods: 
 
Inclusion Criteria: 
1. 
18 years old or above 
2. 
Clinical diagnosis of Parkinson disease by verified by movement disorders expert 
at the initial study visit with at least two cardinal signs of the disease (rest tremor, 
bradykinesia, rigidity, and postural instability). 
3. 
For the monotherapy arm, patients must not be on amantadine, dopamine 
agonists, or levodopa. For the adjuvant therapy arm: Patients must be on a stable dose of 
their current medication for treatment of Parkinson disease which may include any 
combination of the following: amantadine, trihexiphenydil, dopamine agonist, and/or 
levodopa. 
4. 
Patients may continue their stable dose of tricyclic, selective serotonin reuptake 
inhibitor, or serotonin norepinephrine reuptake inhibitor if they are on these medications 
at randomization. 
 
Exclusion Criteria: 
1. 
Catechol-O-Methyltransferase (COMT) inhibitor therapy use 30 days prior to 
start of study (both study arms). 
2. 
Dopamine receptor blocker use (such as quetiapine) one week prior to taking 
study drug 
3. 
For both monotherapy and adjuvant therapy arms: use of MAO inhibitor therapy 
including selegiline or rasagiline within 30 days prior to taking study drug and first 
posturography evaluation.    
 
 
Study Visits: 
 
Screening:  
Patients will be evaluated by movement disorders expert who will confirm diagnosis of 
Parkinson disease as stipulated in inclusion criteria. Blood pressure and heart rate, as well 
as a complete Unified Parkinson Disease Rating Scale (UPDRS) evaluation will be 
performed. 

 
Randomization: 
Subjects will be randomized by facility pharmacy to either placebo or rasagiline 1 mg 
daily for 8 weeks. There will be 5 rasagiline monotherapy and 5 matching placebo 
subjects as well as 5 rasagiline adjuvant therapy and 5 matching placebo subjects.  
 
Computerized dynamic posturography evaluation: 
Subjects will be evaluated at baseline prior to taking first tablet as well as at 4 weeks and 
8 weeks. In the adjuvant therapy arm, subjects will be evaluated on rasagiline but in a 
functional OFF state for their other PD medications. 
 
Functional OFF will be defined as at least 24 hours post last dose of long acting 
dopamine agonist or levodopa extended or continuous release formulations, at least 8 
hours post last dose of immediate release dopamine agonist, immediate release levodopa, 
or trihexyphenidyl.   
 
Subjects will undergo computerized dynamic posturography testing via apparatus 
manufactured by Neurocom, Inc. This device is clinically used for measurement of 
balance impairment. It measures body sway under varying visual and vestibular cues [3]. 
Motor control test (MCT) measuring body sway during small translations of the support 
surface will also be used.  
 
Conclusion of study: 
Subjects will stop taking rasagiline or placebo once their 8 week supply runs out. 
 
Power analysis to determine the number of subjects  
To estimate number of subjects needed for the posturography test, we performed a power 
analysis using the software G*power [4]. For inputs, data from the effect of dopamine 
depleter tetrabenazine on posturography in Huntington’s disease was used [5]. 
 
The strategy composite score here during the tetrabenzine ON state was 79.2, during 
tetrabenzine OFF state it was 63.5. Averaged SD for these two outcomes was 11.5 and 
the total sample size was 10. These data were used to calculate the anticipated effect size. 
This input provided the Effect Size f = 0.6826087 (Table 1).  
 
Input of the effect size value into the G*power with requested α=0.05 and power (1-
β)=0.9, weighing in the repeated measurements (before and after rasagiline) with very 
low correlation among repeated measures resulted in returned total sample size of 10 
subjects Table 1 (please see the table of calculated inputs and outputs below). This total 
number will be randomized into 2 groups of subjects: rasagiline monotherapy and 
placebo study arm. Similarly, there will be 10 subjects in the study arm with rasagiline as 
an adjuvant therapy versus placebo. 
 
F tests - ANOVA: Repeated measures, between factors 
 
Analysis: A priori: Compute required sample size  

Input: 
 
Effect size f                  = 
0.6826087 
 
 
 
α err prob                     = 
0.05 
 
 
 
Power (1-β err prob)           = 
0.9 
 
 
 
Number of groups               = 
2 
 
 
 
Repetitions                    = 
4 
 
 
 
Corr among rep measures        = 
.1 
Output: 
 
Noncentrality parameter λ      = 
14.337066 
 
 
 
Critical F                     = 
5.317655 
 
 
 
Numerator df                   = 
1.000000 
 
 
 
Denominator df                 = 
8.000000 
 
 
 
Total sample size              = 
10 
 
 
Actual power                = 
0.910691 
 
Table 1. G*power software inputs and outputs for statistical power 
 
General approach for statistical evaluation of the study data 
The output of the posturography testing are computer-calculated scores. Though these 
scores are discrete (do not represent a continuous variable), they still may fit the 
requirements of parametric statistical tests. Thus, we will first test the raw scores for 
normal distribution using a Kolmogorov-Smirnov test versus dataset with known 
Gaussian distribution. If the scores are normally distributed, we will determine whether 
data variance is approximately equal in all tested groups. If these conditions are met, we 
will continue data evaluation using repeated measures ANOVA with between factor of 
drug (levels: rasagiline, placebo) and within factor of treatment (levels: before, after). 
Level of significance will be preset to 0.05. Since no multiple comparisons are planned, 
there will be no adjustments of p. 
If we do not find the Gaussian distribution of scores or if the variances among the groups 
are unequal (difference of one order of magnitude or more), we will calculate non-
parametric statistics to determine differences. For this purpose we will use Wilcoxon 
Signed Rank test and evaluate separately rasagiline and placebo groups with p preset to 
0.05. 
 
 
Abbreviations 
COMT: Catechol-O-Methyltransferase 
HD: Huntington’s disease  
MCT: Motor control test 
PD: Parkinson’s disease 
 

 
 
 
References: 
1. Wood BH, Bilclough, Bowron A. Incidence and prediction of falls in Parkinson's 
disease: a prospective multidisciplinary study.  J Neurol Neurosurg Psychiatry 
2002;72:721-725 
2. Ebmeier KP, Calder SA, Crawford JR, et al. Mortality and causes of death in 
idiopathic Parkinson's disease: results from the Aberdeen whole population study. 
Scott Med J 1990;35:173–5. 
3. Ondo WG, Almaguer M, Cohen H. Computerized posturography balance 
assessment of patients with bilateral ventralis intermedius nuclei deep brain 
stimulation. Mov Disord. 2006;21:22243–7.  
4. Faul F, Erdfelder E, Lang AG, Buchner A. (G*Power 3: A flexible statistical 
power analysis program for the social, behavioral, and biomedical sciences. 
Behavior Research Methods 2007:39(2), 175-191. 
https://doi.org/10.3758/BF03193146. 
5. Fekete, R., Davidson, A., Ondo, W.G., and Cohen, H.S. Effect of tetrabenazine on 
computerized dynamic posturography in Huntington disease patients. 
Parkinsonism and Related Disorders 2012;18(7):896-8. 
 
Declarations 
 
Ethics Approval and Consent to Participate 
The study was not registered as no patients were enrolled. The study was approved by the 
New York Medical College Office of Research Administration Institutional Review Board 
under tracking number L-10,768. 
 
Consent for Publication 
Not applicable 
 
Competing Interests 
RF has served as a consultant for Teva Neuroscience, Inc.  
 
Funding 

There was no funding for this study. 
 
Author Contributions 
RF Conception, writing of manuscript. 
 
Data Availability 
Given the absence of funding, data gathering could not commence. No data was gathered. 
 
Acknowledgements 
None 
 
Figure Legends 
Table 1. G*power software inputs and outputs for statistical power