Conditions: Parkinson's Disease
Keywords: Rasagiline
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 96
Healthy volunteers: no

Brief summary:
Parkinson's disease (PD) is a neurodegenerative brain disorder that impairs the ability to perform functions such as grooming, dressing, cooking, and other activities of daily living. PD affected between 4.1 and 4.6 million people worldwide in 2005, and it is projected that up to 9.3 million people will be affected by 2030. Although current pharmacological therapies provide beneficial effects on motor symptoms of the disease (tremor, rigidity, and bradykinesia), intolerable disability eventually develops in most patients. A disease-modifying therapy that slows disease progression is a major unmet medical need in PD. Numerous agents have neuroprotective effects in pre-clinical laboratory models, but none have been shown to have indisputable disease-modifying effects in clinical trials for patients with PD.

The purpose of this research study is to investigate how the brain and motor behavior changes in PD over time in response to rasagiline which is a monoamine oxidase-B(MAO-B) inhibitor. The drug rasagiline will be tested in this study as the MAO-B inhibitor. Rasagiline has been prescribed for many years to treat symptomatic Parkinson's disease. It is FDA approved for the treatment of Parkinson's disease but has not been shown to slow disease progression. The outcome and impact of this study will provide the first evaluation of MAO-B inhibitors at slowing the progression of the nigrostriatal pathway using advanced Magnetic Resonance Imaging (MRI) and functional Magnetic Resonance Imaging (fMRI) methods in PD.

Detailed description:
Participants will receive baseline testing to confirm a diagnosis of Parkinsonism and to determine eligibility in the research study. Half of the participants in this study will be in a group that will receive the study drug (rasagiline), and half will be in a group that will receive a placebo. A placebo is a pill that is made to look like the study drug, but it does not contain any active ingredients. A computer algorithm will randomly decide group assignment (like the flip of a coin). The study drug will be provided at the end of the first visit. The participants will not know which study drug is received, placebo or rasagiline.

During the research study the following test may occur: (1) questionnaires about quality of life and depression; (2) tests to measure strength and motor function; (3) tests to measure cognition; (4) orientation session to learn a precision gripping task; (5) functional MRI scan of the brain; (6) structural MRI scan of the brain.

Arms:
arm 1: This group will receive a 1 mg rasagiline tablet to be taken once daily for one year. In addition, the following test will be performed: a Magnetic Resonance Imaging (MRI), functional Magnetic Resonance Imaging (fMRI), the Montreal Cognitive Assessment, Stroop, Digit Span, Hopkins Verbal Learning Test, Brief Test of Attention, Beck Depression Index, Hamilton Anxiety and Depression Rating Scales, Physical Function Performance Test, and Epworth Sleepiness Scale. arm 2: This group will receive a placebo tablet in the same forum as the rasagiline tablet to be taken once daily for one year. In addition, the following test will be performed: a Magnetic Resonance Imaging (MRI), functional Magnetic Resonance Imaging (fMRI), the Montreal Cognitive Assessment, Stroop, Digit Span, Hopkins Verbal Learning Test, Brief Test of Attention, Beck Depression Index, Hamilton Anxiety and Depression Rating Scales, Physical Function Performance Test, and Epworth Sleepiness Scale.

Interventions: intervention 1: Rasagiline intervention 2: Placebo intervention 3: Magnetic Resonance Imaging intervention 4: functional Magnetic Resonance Imaging intervention 5: Physical Function Performance Test
Intervention descriptions: intervention 1: Rasagiline will be taken for one year at the dose of 1mg a day. and subjects will undergo functional and structural brain imaging to determine if rasagiline is slowing the progression of Parkinson's Disease in the brain. intervention 2: A placebo tablet will be taken for one year, once a day, and at the same dose of 1mg. subjects will undergo functional and structural brain imaging to be compared with the group taking the rasagiline intervention. intervention 3: This test will be performed at baseline and one year. intervention 4: This test will be performed at baseline and one year. intervention 5: This test will be performed at baseline and one year.

Protocol document:
Prot_SAP_000.pdf: 
 
 
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PROTOCOL 
 
1. PROJECT TITLE:   
 
Image Parkinson’s Disease Progression Study 
 
2. INVESTIGATOR(S):   
 
David Vaillancourt, Ph.D., Principal Investigator 
Michael Okun, M. D., Co-Investigator 
Nikolaus McFarland, M.D., Co-Investigator 
Irene Malaty, M.D., Co-Investigator 
Song Lai, PhD., Co-Investigator 
Catherine Price, PhD., Co-Investigator 
Aparna Wagle Shukla, M.D., Co-Investigator 
David Arpin, Ph.D., Co-Investigator 
 
3. ABSTRACT 
 
The purpose of this research study is to investigate how the brain and motor behavior changes 
Parkinson’s disease over time in response to rasagiline. The drug rasagiline will be tested in this study. 
Rasagiline has been prescribed by doctors for many years to treat symptomatic Parkinson’s disease. It 
is FDA approved for the treatment of Parkinson’s disease but has not been shown to slow disease 
progression. 
 
4.  SIGNIFICANCE 
 
PD is a neurodegenerative brain disorder that impairs the ability to perform functions such as grooming, 
dressing, cooking, and other activities of daily living. PD affected between 4.1 and 4.6 million people 
worldwide in 2005, and it is projected that up to 9.3 million people will be affected by 20301. Although 
current pharmacological therapies provide beneficial effects on motor symptoms of the disease (i.e., 
tremor, rigidity, and bradykinesia), intolerable disability eventually develops in most patients2.  A 
disease-modifying therapy that slows disease progression is a major unmet medical need in PD3. 
Numerous agents have neuroprotective effects in pre-clinical laboratory models, but none have been 
shown to have indisputable disease-modifying effects in clinical trials for patients with PD2.  According 
to Olanow and colleagues4: “A limiting factor is the requirement for a clinical end point that reliably 
measures disease progression and is not confounded by the study intervention’s effects on symptoms.”  
This is the primary reason that biomarkers of progression in PD have been sought in major research 
initiatives including the Michael J. Fox Parkinson Progressive Marker Initiative and the NINDS 
Parkinson’s Disease Biomarker Program.  Progression markers could serve as end-points in clinical 
drug trials, and this is the same model used to evaluate disease-modifying therapeutics in diseases 
such as cancer5, 6 and multiple sclerosis7, 8. 
 
In the past three decades a revolution has occurred in the ability to image brain structure and function, 
and the insights that such studies have provided into the pathogenesis of various diseases have 
dramatically transformed the field.  The Vaillancourt laboratory has been part of this revolution in the 
area of PD.  In 2005, our group was NIH funded to evaluate novel task-based fMRI assays of the 
healthy basal ganglia.  The studies led to new insights and a model of the healthy basal ganglia related 


 
 
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to specific aspects of force control9-12, and subsequently spurred a competitive renewal and a series of 
cross-sectional studies comparing early stage PD and control individuals13-15.  Our work has repeatedly 
found that regions of the basal ganglia such as the putamen, as well as motor cortex and SMA, show 
reduced BOLD activity during force control studies15, 16, and that the severity of PD measured cross-
sectionally was correlated with the BOLD activity in the putamen14.  Most recently, we have found that 
the BOLD activity in the putamen, motor cortex, and SMA decrease in the PD group after one-year of 
progression, with no changes in a control group17.  In addition to these innovative studies using BOLD 
fMRI, we also used diffusion MRI and a novel bi-tensor model as a tool to assay the degeneration 
occurring within the PD substantia nigra.  Our group found that diffusion MRI can detect changes in the 
substantia nigra in cross-sectional studies18-20.  Most recently, our laboratory found that diffusion MRI 
tracks progression of the substantia nigra over one year, and that baseline measures from diffusion 
MRI predict the rate of clinical progression of bradykinesia in the subsequent year21.  These two major 
innovations using BOLD fMRI and diffusion MRI were developed with NIH funding, and we now have 
non-invasive MRI-based biomarkers of nigrostriatal and cortical progression in PD. 
 
Now that non-invasive progression markers of brain structure and function exist, our next step is to 
demonstrate how imaging technology can effectively evaluate promising pharmacological therapies in 
PD.  Thus far, several studies in PD have advanced the hypothesis that the selective monoamine 
oxidase type B (MAO-B) inhibitor could provide not only a better control of parkinsonian symptoms, but 
could also have disease-modifying properties. MAO-B inhibitors stop the breakdown of dopamine and 
thereby allow the nigrostriatal neurons to sustain firing patterns.  The neuroprotective potential of MAO-
B inhibitor administration has been tested in pre-clinical rodent models of PD, where MAO-B inhibitors 
significantly counteracted cell loss in the substantia nigra following striatal injection of 6-
hydroxydopamine (6-OHDA)22, and exerted a significant neuroprotective effect against lactacystin-
induced neurostriatal degeneration23. Although MAO-B inhibitors have been associated with a 
reduction in the clinical ratings of PD (Unified PD Rating Scale) and a reduction of the “off” time in PD, 
establishing its long-term disease modifying quality has yet to be determined.  A recent delayed start 
designed study demonstrated its potential as a disease modifier at 1mg/day but not at 2mg/day24, 25. 
As such, the goal of this project is to evaluate our novel scanning techniques to pick up changes related 
to a common PD drug (a MAO-B inhibitor at 1mg/day) at slowing the progression of PD. We will use 
diffusion MRI and functional MRI assays as the primary endpoints. 
 
5. INNOVATION 
 
We provide three specific examples of how this work is innovative. 
1.  The proposed research will be the first randomized, prospective study to determine if an MAO-
B inhibitor slows the progression of MRI-based biomarkers of PD progression. 
2.  We will use a novel bi-tensor analysis algorithm for diffusion MRI to estimate the fractional 
volume of free-water within the substantia nigra26-28.  This technique has shown elevated free-water 
in the substantia nigra of PD relative to controls in two separate cohorts, one from a single site study 
and another from a multi-site study29. 
3.  We will use the innovative grip force fMRI paradigm developed by our group13, 30.  Our group is 
one of the only labs in the world that manufacture the custom force sensors for this application, 
which provide a reliable and robust measurement of the motor-related BOLD signal in humans. 
 
 
 


 
 
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6.  DIFFUSION MRI AS A BIOMARKER OF SUBSTANTIA NIGRA PROGRESSION 
 
Diffusion MRI is a technique that examines biological tissue using MRI pulse sequences sensitized to 
the local microstructural characteristics of water diffusion. Diffusion MRI can provide scalar measures 
of interest, where fractional anisotropy (FA) is the main measure used in neurological studies. Diffusion 
MRI has classically been applied to white matter tracts31, 32. Our laboratory and others have used 
diffusion MRI to examine gray matter areas19, 33, 34.  In white matter, FA reflects many factors, including 
axonal density and degree of myelination35, 36.  In gray matter, FA has been related to the number of 
dopaminergic cells in the substantia nigra33, although many other factors could influence FA 
measurements.  We have used diffusion MRI and a single tensor model to study the substantia nigra 
in de novo PD. 
 
6.1. Using a single tensor model for fractional anisotropy.  We published a study comparing FA in 
the ventral substantia nigra of 14 de novo PD patients with 14 control subjects19.  De novo refers to PD 
patients who have never taken anti-PD medications.  
We observed that FA was reduced in the ventral and 
posterior substantia nigra of early stage PD patients 
compared with healthy control subjects.  Since prior 
work has shown that the number of dopaminergic cells 
is related to measures from diffusion MRI33, our findings 
were consistent with the established pattern of PD-
related loss of dopaminergic cells in the ventral and 
posterior substantia nigra.  Since our initial publication, 
several laboratories have replicated the reduced 
fractional anisotropy in the substantia nigra of PD 37-39.  
This set of findings has taught us that diffusion MRI 
can detect changes in the substantia nigra in early 
stage de novo PD patients compared with controls. 
 
6.2. Bi-tensor model to overcome some of the 
limitations of fractional anisotropy: Evidence from 
a single-site and multi-site study of PD.  Although 
several studies have found reduced FA in the 
substantia nigra of PD, other studies have not found FA 
difference between patients with PD and controls40.  
The reason for this may be due to the limitations in the 
single tensor analysis model, and the bi-tensor analysis 
model was introduced to overcome these limitations.  
The FA measure is limited as a measure of tissue 
microstructure, since atrophy-based partial volume 
free-water contamination can bias the diffusion 
index41.  If gray matter voxels contain considerable 
free-water, then diffusion indices such as mean 
diffusivity can be elevated and the fractional anisotropy 
measure can be reduced42, 43. 
 
 
Figure 1. A, shows the pipeline for registering 
diffusion data to MNI space using the T2 MNI 
template.  Regions are hand-drawn for each subject 
in MNI space on the b0 image and quantified on the 
free-water map in B.  C, increased free-water in the 
posterior SN from the University of Florida cohort (28 
PD, 20 control).  D, increased free-water in the 


 
 
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Recently, free-water diffusion MRI analysis using a bi-tensor model was developed by Dr. Ofer 
Pasternak to explicitly estimate the contribution of freely diffusing water molecules within the voxel27, 
41.  This free-water measure is expected to increase with atrophy-based neurodegeneration8, 26.  When 
the free-water component is eliminated, the remaining signal provides a corrected fractional anisotropy 
value (FAT) and corrected mean diffusivity value (MDT) within the tissue of interest.  Figure 1A shows 
the free-water analysis pipeline, and Figure 1B shows the free-water map in the substantia nigra.  Bright 
colors indicate high free-water.  Since substantia nigra degeneration occurs mostly in the posterior 
region of the substantia nigra in PD (ie. ventrolateral tier) 44-46, we tested the hypothesis that free-water 
would be elevated in the posterior substantia nigra of PD. 
 
We evaluated free-water in a group of people with early stage PD (N = 28) and healthy controls (N=20) 
at the University of Florida.  These controls were selected to match PD based on age and sex.  PD 
patients were off-medication for more than 12 hours.  As seen in Figure 1C, free-water in the ventral 
and posterior substantia nigra is increased in PD.  This is the same region where dopaminergic cells 
are typically damaged in post-mortem tissue.  In a validation analysis performed on the multi-site cohort 
from 
the 
Michael 
J. 
Fox 
Foundation 
Parkinson 
Progressive Marker Initiative (PPMI), we applied the same 
regions of interest (regions are in MNI space) shown in 
Figure 1B to the multi-site PPMI cohort of de novo PD 
(N=78) and controls (N = 56).  These subjects were 
acquired on 8 different 3T MRI magnets across the PPMI 
sites.  There is increased free-water in the ventral and 
posterior substantia nigra of the PPMI cohort of PD 
compared with controls (Figure 1D), which is the same 
region found for the University of Florida cohort.  The FAT 
value was not different between groups in either cohort, 
indicating that the free-water component of the bi-tensor 
model is the actual index of change in PD.  In summary, 
this set of findings has taught us that free-water 
measurement using the bi-tensor model is a very 
robust technique that is now replicated in two 
separate cohorts for measuring the microstructure of 
the substantia nigra of PD. 
 
 
Figure 2. Free-water in the SN in 25 PD and 19 
controls at baseline and one-year (mean + SE).  
The interaction between group and time was 
significant.  PD had increased free-water from 
baseline to Year 1 (p < .005).  Controls did not 
change significantly across time (p > .10).   


 
 
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6.3. Free-water measurements of the substantia nigra are a progression marker in PD.  We have 
followed a group of 25 PD patients and 19 controls from baseline to one year using diffusion MRI.  All 
MRIs were collected following 12 hours without Parkinsonian medications. The free-water 
measurement was assessed within the posterior substantia nigra using the bi-tensor analysis outlined 
in Figure 1A.  P-values were corrected using the false-
discovery rate (FDR).  Figure 2 shows that we observe a 
significant group by time interaction (pFDR < 0.05), such 
that the PD patients have a greater increase in free-water 
after one year than the control group.  Further inspection 
using a paired t-test in the PD group indicates that the 
increase in free-water in the posterior substantia nigra 
increased at one year compared with baseline (pFDR < 
0.006).  PD had elevated free-water compared with 
controls at both time points (pFDR < 0.005).  Another key 
finding is shown in Figure 3.  Baseline free-water values in 
the posterior substantia nigra predicted the changes in 
bradykinesia scores (r = 0.74, P < 0.001) over the next 
year.  In control regions of interest including subthalamic 
nucleus and lateral ventricle we did not find any change 
after one year for PD and controls, and we do not observe 
a group effect in the control regions between PD and 
controls (p’s > 0.5).  This suggests that the observed 
change in free-water is specific to the substantia nigra and 
not related to scanner performance.  It was recently noted 
in a paper by Kordower and colleagues46 that the number 
of melanized neurons in the substantia nigra may be 
progressively decreasing with disease duration in PD.  The free-water measurement seems to be 
detecting this subtle change in cellular architecture, and provides the first published MRI 
progression marker of PD over a one year 
period of time. 
 
7.  TASK-FMRI AS A BIOMARKER OF 
PUTAMEN 
AND 
MOTOR 
CORTICAL 
PROGRESSION  
 
 
Figure 3.  Scatterplot and regression of 
predicted change in bradykinesia and actual 
change in bradykinesia for patients with 
Parkinson’s disease (r = 0.74; p < 0.001).  The 
regression model consisted of baseline free-
water and sex, which were both significant 
predictors of the change in bradykinesia over 
one year. 
 
 
Figure 4. A, shows the force sensor.  B, shows calibration 
of the sensor (N) to the change in wavelength (nm).  C, is 
the grip setup during task-fMRI.  D, is the paradigm used in 
our studies.  E, shows the force pulses during one 30s block 
with 10 force pulses. 


 
 
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7.1. Development of task-fMRI for studying motor physiology.  fMRI is a technique that has 
provided enormous advances in understanding the breakdown in functional activity and functional 
connectivity within the human brain of various diseases that include PD and Alzheimer’s disease 47-49.  
Over the past decade, our group has developed new techniques to study motor physiology in humans 
with PD during task-fMRI, with the overall goal to make task-fMRI more repeatable, reliable, and 
consistent for disease progression and drug evaluation studies. 
 
We have designed novel MRI compatible force sensors in the PI’s lab with R01 funding (Figure 4A), 
and these sensors have excellent linearity, sensitivity, and accuracy (Figure 4B).  In Years 1-4 of the 
R01, we built up a considerable understanding of the blood oxygenation level dependent (BOLD) fMRI 
signal during motor tasks9, and in particular found that the BOLD fMRI signal is dependent upon the 
amplitude of force and duration of force pulses 
11, 50.  In Years 5-6 of the R01, we decided to 
implement a grip force paradigm that would 
yield a repeatable fMRI BOLD signal in cross-
sectional studies of PD versus controls.  We 
required subjects to generate multiple force 
pulses 
at 
15% 
of 
maximum 
voluntary 
contraction with a fixed duration of 2 s for each 
force pulse15. The rationale for using this task 
was that: 1) it activates the basal ganglia, motor 
cortical, and cerebellar networks in healthy 
subjects11, 51, 2) PD patients have difficulty 
contracting and relaxing muscle force as shown 
in numerous laboratory studies52-54, and 3) this 
type of repetitive task of contracting and relaxing 
muscle is instrumental in the motor section of the Unified Parkinson’s Disease Rating Scale (UPDRS)55. 
 
Using the experimental paradigm in Figure 4C-E, we have made a series of important discoveries 
regarding the BOLD fMRI signal in people with PD.  We have consistently found that BOLD signals in 
the putamen and motor cortex are reduced in PD compared with controls15, 56, 57, and the severity of 
PD motor symptoms correlates with the BOLD signal in putamen 14.  We also observe strikingly 
consistent findings across our cohorts, even when using different 3T MRI systems.  Figure 5 shows the 
results from two different cohorts of control and PD.  Figure 5A shows findings by Prodoehl and 
colleagues in a cohort of de novo PD and controls using a GE 3T at University of Illinois at Chicago14.  
Figure 5B shows findings from Burciu and colleagues in a cohort of early stage PD and controls using 
a Philips 3T at University of Florida58.  Please note that the scale is the same on each plot, and that the 
mean values are consistent across studies.  It is clear that this task-fMRI paradigm is a robust 
technique for detecting differences in PD versus controls. 
 
Figure 5. A, shows findings from the task-fMRI study by 
Prodoehl and B, shows results by Burciu et al.  Both plots 
show the mean + 1SE across the two cohorts.   


 
 
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7.2.  Progression of the task-fMRI BOLD signal in PD 
over one year.  In our current cycle of funding, we have 
been conducting a longitudinal study of PD over a one year 
period.  We have studied 40 PD patients and 25 control 
subjects at baseline and following one year of progression 
using task-fMRI described in Figure 458.  PD patients were 
tested 
following 
a 
14-hour 
withdrawal 
from 
antiparkinsonian medication. A region of interest (ROI) 
approach was employed to examine changes in BOLD 
signal in putamen, hand area of the primary motor cortex 
(M1), supplementary motor area (SMA), and hand area of 
the cerebellum (lobules V-VI). The ROIs used in the study 
were drawn a priori, and are shown in Figure 6.  A 
MANOVA was used to examine the change in BOLD 
signal over a one year period, and p-values were corrected 
for multiple comparisons using the false-discovery rate 
(FDR).  Figure 7 shows no functional change over the 
course of a year in any of these regions for controls. 
However, in PD the functional activity of the putamen, 
hand area in M1, and SMA decreased significantly from 
baseline to one year follow-up (pFDR values < 0.05). 
Other changes in PD included an increase in disease 
severity based on the motor section of the Movement 
Disorder Society Unified Parkinson's Disease Rating 
Scale (MDS-UPDRS-III) and decrease in bimanual 
coordination tested using the Purdue Pegboard (pFDR 
values < 0.05). No decline in depression or cognition was 
detected in either controls or PD. In summary, early 
stages of PD are associated with decreases in the 
functional activity of key nodes within the basal 
ganglia and motor cortex but not the cerebellum. 
 
8. CHOOSING A DRUG TO TEST THE IMAGING 
BIOMARKERS 
OF 
PD 
PROGRESSION: 
MAO-B 
INHIBITORS AND PRELIMINARY CROSS-SECTIONAL 
FINDINGS 
 
8.1.  MAO-B inhibitors in animals and humans.  Several 
studies in PD have advanced the hypothesis that the selective monoamine oxidase type B (MAO-B) 
inhibitor rasagaline provides symptomatic improvement in parkinsonian motor symptoms, and could 
possibly have disease-modifying properties at a 1 mg/day dose59, 60. Since there is a paucity of evidence 
in the human for a disease modifying drug, a MAO-B drug may be the best available therapy to test an 
imaging biomarker. A couple of decades ago the MAO-B inhibitor selegiline was tested (DATATOP), 
and recently the MAO-B inhibitor rasagiline was identified and developed as an anti-PD drug and 
possibly for disease modification61. In preclinical studies, MAO-B inhibitors have shown a potential for 
neuroprotective activity62, 63.  The neuroprotective potential of the MAO-B inhibitor rasagiline has been 
tested in rodent models of PD, where the drug significantly counteracted cell loss in the substantia nigra 
 
Figure 6. Shows regions of interest used in the 
task-fMRI longitudinal study.   
 
Figure 7. shows difference in BOLD signal (1 
Year – Baseline) for controls and PD.  Here, a 
negative change in BOLD signal indicates a 
decrease and positive change in BOLD signal 
indicates an increase.  P values are FDR 
corrected at p < 0.05.


 
 
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following striatal injection of 6-hydroxydopamine (6-OHDA)64, and exerted a significant neuroprotective 
effect against lactacystin-induced nigrostriatal degeneration65. In humans, rasagiline at 1.0 mg/day, 
causes almost total inhibition of platelet MAO-B66. In a multi-center, randomized, double-blind, placebo-
controlled clinical investigation of rasagiline monotherapy in 404 subjects with early, otherwise 
untreated, PD67, 68, rasagiline was well tolerated at dosages of 1.0 and 2.0 mg/day, and patients 
receiving rasagiline had better motor function after 6 months of treatment than those receiving placebo.  
In 2009, Olanow and colleagues4 performed a Phase III multi-center clinical trial to determine if the 
MAO-B inhibitor rasagiline at 1 mg/day or 2 mg/day had disease modifying qualities.  The primary 
endpoint was the motor section of the UPDRS.  The delayed-start paradigm was used to evaluate the 
possibility of disease modification versus symptomatic effects of rasagiline.  Early-start treatment with 
rasagiline at a dose of 1 mg/day met all end points in the primary analysis: a smaller mean (±SE) 
increase (rate of worsening) in the UPDRS score between weeks 12 and 36, less worsening in the 
score between baseline and week 72, and noninferiority between the two groups with respect to the 
rate of change in the UPDRS score between weeks 48 and 72. However, all three end points were not 
met with rasagiline at a dose of 2 mg/day, since the change in the UPDRS score between baseline and 
week 72 was not significantly different in the two groups.  The failure at 2 mg/day led the USA Food 
and Drug Administration to vote against rasagiline for a labeled indication as a disease modifying 
therapy for PD, though much debate has surfaced about this issue.  Many experts believe it is possible 
that 2mg/day was not as effective as 1 mg/day or it was possible that 2 mg/day had a greater 
symptomatic effect and masked the disease modifying effect. 
 
What is clear from this work was that 1 mg/day was well tolerated, has beneficial effects on PD 
symptoms, and could have disease-modifying qualities for PD.  As pointed out by Olanow and 
colleagues4, the lack of a viable biomarker of the nigrostriatal system causes significant 
problems when interpreting the effects of potential disease modifying therapies, and an imaging 
endpoint could have been helpful in the two arms of this study.  This is because the symptomatic 
effects of the drug could mask the disease-modifying effects if they exist.  Now that we have developed 
free-water diffusion MRI and task-based BOLD fMRI as viable progression markers in PD, we are now 
well positioned to test our imaging biomarkers using a placebo-controlled, double-blind randomized 
design with the MAO-B inhibitor rasagiline at the 1 mg/day dose. 
 
8.2. Retrospective preliminary data for MAO-B inhibitor effects captured by PD imaging 
biomarkers.  We examined the retrospective data from our longitudinal imaging studies by asking the 
question if the baseline imaging was different between patients with PD already taking rasagiline versus 
PD not taking rasagiline.  Sixteen PD patients who were taking rasagiline prior to the time of testing (13 
patients on 1 mg/day, 3 patients on 0.5 mg/day), 18 PD patients who were not taking rasagiline or 
another MAO-B inhibitor, and 18 controls were included in the study. The average duration that patients 
took rasagiline was 8 months prior to the testing.  The two PD groups were matched for age, sex, 
disease duration, motor severity based on the UPDRS, and cognitive status based on the Montreal 
Cognitive Assessment (MoCA). Primary outcomes included: 1) task-fMRI BOLD signal within the 
posterior putamen and 2) free-water within the posterior substantia nigra. 
 


 
 
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Figure 8A illustrates the between-group differences in BOLD signal in the contralateral posterior 
putamen.  Figure 8B shows the between-group differences in free-water in the posterior substantia 
nigra. P-values were corrected using the false-discovery rate (FDR).  A significant group effect was 
found for posterior putamen BOLD signal (F2,48 = 11.81, pFDR = 0.002) as well as for substantia nigra 
free-water (F2,48 = 12.45, pFDR = 0.002). Overall, PD patients had a lower BOLD signal and higher 
free-water level compared to controls. When comparing the two patient groups, PD who were not taking 
rasagiline were the most affected, having a significantly lower BOLD signal and higher free-water level 
than PD who were taking rasagiline (pFDR values < 0.05) (Figure 8A-B). In control regions where we 
would not anticipate between group effects, we found no functional and diffusion MRI differences (i.e., 
contralateral angular gyrus and bilateral STN) (pFDR values > 0.05).  As shown in Figure 8C, a 
significant group effect was found for bimanual coordination (Purdue Pegboard both hands) (F2,48 = 
10.34, pFDR = 0.004).  PD 
patients placed significantly less 
pegs on the pegboard with both 
hands than controls (pFDR 
values < 0.05), and PD who 
were taking rasagiline placed 
significantly more pegs than PD 
who were not taking rasagiline 
(pFDR values < 0.05). 
 
The current retrospective data 
provides neuroimaging and motor dexterity evidence that PD patients taking the MAO-B inhibitor 
rasagaline have a better functional and structural integrity of the nigrostriatal circuit, as well as improved 
bimanual coordination. The results highlight the potential benefit of using functional and diffusion MRI 
measures in future prospective, randomized placebo-controlled studies of rasagiline. 
 
9. SPECIFIC AIMS: 
 
Aim 1. Effects of an MAO-B Inhibitor on the Progression of Free-water of the SN in PD. We will 
conduct a 12-month study in PD to test the hypothesis that the MAO-B inhibitor will slow the progressive 
increase of free-water accumulation in the SN.  Since we have found that free-water in the SN relates 
to PD motor symptoms and bradykinesia, our secondary outcomes will evaluate if the change in free-
water from the SN relates to changes in the progression of the PD motor symptoms and bradykinesia.  
 
Aim 2. Effects of an MAO-B Inhibitor on the Progression of the BOLD signal of the putamen, M1, 
and SMA in PD.  We will study the same patients with PD as in Aim 1.  We test the hypothesis that the 
MAO-B inhibitor will slow the progressive decrease of the BOLD signal in the posterior putamen, M1, 
and SMA.  Since we have found that the BOLD signal from the posterior putamen relates to PD motor 
symptoms and bradykinesia, our secondary outcomes will evaluate if the change in the BOLD signal 
from the posterior putamen relates to changes in the progression of the PD motor symptoms and 
bradykinesia. 
 
This study is a prospective biomarker study to evaluate how an MAO-B inhibitor affects the progression 
of two novel, non-invasive biomarkers of the nigrostriatal regions and motor cortex.  We will also assess 
a battery of secondary outcomes to monitor motor performance, cognitive status, and emotional status.  
The follow up questionnaires will assess additional measurements relating to long term (>18 months) 
health care outcomes and quality of life. We monitor adverse events carefully and have a data safety 
Figure 8. A, shows findings from the task-fMRI, B, shows findings from free-
water in the substantia nigra, and C, shows findings from the Purdue Pegboard 
test using both hands.  Both plots show the mean + 1SE.   


 
 
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and monitoring board.  The outcome and impact of this study will provide the first evaluation of 
MAO-B inhibitors at slowing the progression of the nigrostriatal pathway using advanced dMRI 
and fMRI methods in PD.   
 
10. RESEARCH PLAN: 
 
Recruitment 
 
To recruit subjects to the study, the Movement Disorder Centers database administrators (UF IRB 416-
2002), neurologists who work at UF Health, UF Health Jacksonville, the Malcolm Randall VA Medical 
Center, and the University of Buffalo; and study coordinators at the Laboratory for Rehabilitation 
Neuroscience will identify qualifying candidates. They will then refer them to the PI, Co-PI, and other 
research personnel via email, who will contact potential candidates through phone or email who they 
believe are eligible to take part in this study. We will also send advertisements to local Parkinson’s 
disease support groups and use word of mouth. 
 
We will also plan on pre-screening the Center for Movement Disorder Clinic. This will be done by the 
PI and study coordinators. If a participant is identified who meets inclusion/exclusion criteria, their 
provider will be contacted by either the PI or the study coordinators. The provider will be asked to 
approach the participant about the study after their standard clinic visit. If the participant agrees, they 
can contact us directly or give permission to be contacted by the PI or study coordinators.  
 
All participants that are recruited outside of the Movement Disorders Center will receive a neurologic 
evaluation by the collaborating neurologists to confirm a diagnosis of Parkinsonism. 
 
We will also use flyers to recruit additional participants. We will hang flyers as well as make an 
announcement on the University of Florida radio station (89.1 – WUFT). 
 
Study Design 
 
The overall study design is shown in Figure 9.  Referral and screening occur, followed by baseline 
testing.  This includes the primary endpoints using diffusion MRI and task-fMRI, in addition to a test 
battery of secondary motor and cognitive tests.  Patients will then be randomized to either the active 
drug arm or placebo drug arm according to recommendations by our statistician Dr. Sam Wu.  Next, 
patients will undergo 1-year follow-up testing, which is the same testing that occurred at baseline.  The 
1-year follow-up testing may be delayed no longer than 90 days, due to scheduling conflicts or 
unforeseeable circumstances.   This may include an extension of the study medication that will be 
determine by the P.I.  The blinded data analysis will occur following the 1-year follow-up testing.  After 
locking the data, final statistics will be performed in consultation with the statistician Dr. Wu.   


 
 
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Blinding data collection and analysis  
 
As shown in Figure 9, the baseline testing is performed prior to subjects entering the intervention.  The 
coordinator will perform the evaluations.  The UF Health Pharmacy will receive the randomization by 
Dr. Sam Wu, and then prepare the appropriate medication (placebo or active drug) for each patient.  
The patients will not know whether they receive placebo or active drug.  During the 1-year drug trial, 
the coordinator will call each patient every 3 months to monitor any adverse events or issues that arise.  
The coordinator will immediately report any adverse events to the referring neurologist, Dr. Vaillancourt 
and the Data Safety Monitoring Board led by Dr. Irene Malaty (Neurologist), Dr. Christopher Hess 
(Neurologist), and Dr. Stephen Coombes (Imaging expert).  Drs. Malaty, Hess, and Coombes will 
monitor patient safety and other issues.  All data analyses will be performed blinded to the drug status 
of each patient.  Once the data are locked, the group status will be unlocked by Dr. Wu, and final 
statistics will be performed. 
 
Inclusion criteria 
 
We will recruit 96 patients with clinically diagnosed PD. For the PD diagnosis, we will use the UK PD 
brain bank diagnostic criteria implemented by a movement disorders trained neurologist69, 70.  We will 
include early stage PD within 5 years of diagnosis who have never taken rasagiline.  We choose 5 
years since diagnosis to focus on early stages of PD, where MAO-B inhibitors have shown the most 
promise.  PD are eligible to participate if they are age 40-77, Hoehn and Yahr stage < or equal to 2 
when on medication, and able and willing to sign informed consent to be randomized to the placebo or 
active drug arm.   
 
Exclusion criteria 
 
As necessitated by the risks of Magnetic Resonance Imaging, patients who have any type of implanted 
electrical device (such as a cardiac pacemaker or a neurostimulator), or a certain type of metallic clip 
 
Figure 9. Flow chart for the overall study design, baseline testing, intervention, 1-year follow-up testing, and data 
analysis. 


 
 
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in their body (i.e., an aneurysm clip in the brain), are not eligible for participation in the MRI portion of 
the study.  Individuals who are claustrophobic will also be excluded from participation. In addition, 
women who are or might be pregnant and nursing mothers are not eligible. Pregnancy tests will be 
carried out for each female subject prior to the MRI scan. Finally, individuals with psychiatric disorders 
or dementia will be excluded, along with other neurologic and orthopedic problems that impair hand 
movements and walking. 
 
Individuals who have a history metalworking involving cutting processes such as grinding, filing, 
shaving, and threading, will need radiological clearance to participate in this study. Specifically, 
individuals who report a history of metalworking will be referred to Radiology at Shands UF for an 
orbitofrontal x-ray. In addition, individuals who have sustained an eye injury involving metal will also be 
referred to Radiology at Shands UF for an orbitofrontal x-ray. Shands at UF will provide a written report 
stating whether the individual is safe for imaging at 3 Tesla. All expenses related to this procedure will 
be covered by the PI. 
 
Patients with a prior stroke or brain tumor are excluded.  Patients will be excluded if they are unwilling 
to comply with the study procedures.  
 
Reimbursement 
 
Participant will receive $100.00 for each visit to the laboratory and completing the additional follow up 
questionnaires. If they are traveling to the Gainesville (University of Florida) area from more than 50 miles 
away, their transportation costs to and from the testing site and additional meal costs will be reimbursed. 
Finally, during long testing sessions, food and beverages for the participant and any family members 
and/or caregivers that accompany them to the visit will be provided at no expense to them. 
 
Baseline and Longitudinal Testing Schedule 
 
Patients and control individuals will be tested at baseline and following one year. The testing for 
Parkinson’s Disease patients will occur when the patient is off overnight withdrawal from the medication 
prescribed to them by the referring neurologist.  The PI has successfully accomplished off medication 
testing in over 300 patients, and this includes all of the patient groups in this research 72-74.  Patients 
will be driven to the facility by a caretaker or a car service will be arranged for the patient.  We have a 
wheel chair on-site and an MRI compatible gait belt should the patient need help moving to the testing 
facility at UF.  The testing for baseline and 1-year will be the same as described below.   
 
Clinical measures 
 
Important clinical measures to be used in this study include: 1) data about clinical movement disorder 
history, age, gender, height, weight, and other medical conditions; 2) clinical neurological examination; 
3) tests assessing cognitive abilities including: the Montreal Cognitive Assessment, Stroop, Digit Span, 
Hopkins Verbal Learning Test, COWA and Animals, and Brief Test of Attention; 4) measures of anxiety, 
depression, and apathy (Beck Depression Inventory, Hamilton Anxiety and Depression Rating Scales, 
Metacognitive Awareness Inventory); 5) Parkinson’s disease related quality of life (PDQ-39, Modified 
Schwab and England Activities of Daily Living Scale); 8) tests regarding sleep habits (Epworth 
Sleepiness Scale and Rapid Eye Movement Behavior Disorder Questionnaire); 9) questionnaires about 
any adverse events that occurred over the past year; and 10)  measures relating to long term healthcare 
outcomes and quality of life (Follow up Patient Questionnaire and the PDQ-39).  


 
 
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Brain Structure Measures 
 
We will be using the research dedicated 3T MRI scanner in the McKnight Brain Institute to obtain 
diffusion tensor imaging, T1 weighted, and T2 weighted images 19, 74 at the time at which it is available 
for use. Participants will be given a disc containing the MRI images collected during their scan. They 
will be informed that they will not be receiving any kind of clinical feedback related to these images, 
and that the images are for their own use. 
 
Brain Function Measures 
 
We will be using the research dedicated 3T MRI scanner at the McKnight Brain Institute to obtain 
functional magnetic resonance imaging (fMRI) data during the production of grip force production tasks 
12, 75, 76.  Participants will use their hand to squeeze an MRI compatible grip force transducer in the MRI 
unit.  This is a fiber optic transducer that is fully compatible with MRI.  The PI has used this equipment 
safely at 3T for over 10 years and in numerous published studies.  When producing force, the 
participants will view the amount of force they generate when viewing the visual feedback on a MRI 
compatible visual display while lying inside the scanner. 
 
Physical Performance Measures 
 
1.  The Physical Functional Performance Test (tests the ability of the individual to perform everyday 
tasks).  Subjects will be asked to complete as set of everyday tasks such as picking up a slipper from 
the floor 77.  (See Appendix 1 - attached protocol/scale). 
 
2.  The 6 minute walk (tests functional walking endurance). Subjects will be asked to walk at a 
comfortable pace for 6 minutes.  The distance walked along with blood pressure and pulse rate will be 
measured.  Cadence and stride length will be measured during a portion of the 6 minute walk test.  
(See Appendix 1 - attached protocol/scale). 
 
3.  Purdue Pegboard measures how well an individual can perform fine motor tasks using the hands 78 
and has been previously used in assessing Parkinson’s disease 79. 
 
4. Movement Disorder Society (MDS)-sponsored version of the Unified Parkinson’s Disease Rating 
Scale (UPDRS). The MDS-UPDRS has four parts: Part I (non-motor experiences of daily living), Part 
II (motor experiences of daily living), Part III (motor examination) and Part IV (motor complications). 
This rating scale will be video recorded with the participant’s permission to ensure reliability of ratings.  
 
6. The hand grip dynamometer test measures maximum hand grip strength. Participants apply as much 
grip pressure as possible on the dynamometer. Three trials will be completed with each hand. 
 
7. The Dynamic Gait Index monitors the participant’s gait as well as how well a participant is able to 
change gait speed, direction, etc. 
 
 
 
 


 
 
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Follow Up Questionnaires 
 
Additional questionnaires will be administered at >18 months past baseline visit that assess long term 
health care outcomes and quality of life. Participants will fill out an amended informed consent form, 
delivered by mail or over the phone, prior to administering the questionnaires. The questionnaires will 
be administered over RedCap or distributed to the participant via mail, based on the participant’s 
preference. For individuals who elect to receive the questionnaires by mail, they will be provided with 
a pre-addressed and pre-stamped envelope to return the questionnaires. Written instructions on how 
to complete the questionnaires will also be provided. If participants have any questions regarding how 
to complete the forms, the study team is available to answer any questions via phone call. The purpose 
of the PDQ-39 questionnaire is to quantify current quality of life outcomes for Parkinson’s disease. The 
Follow Up Patient Survey measures health outcomes, such as to quantify the number of hospitalizations 
and reasons for hospitalizations, current therapies, living situation (i.e. independent at home or skilled 
care), and whether or not a subject has a regular caregiver each year following the baseline visit.  
 
Statistical Analysis 
 
Dr. Samuel Wu is our statistician who will oversee the statistics in this project.  Demographic and 
baseline levels of clinical variables will be compared between the MAO-B inhibitor and the placebo 
groups using the two-sample t-test or chi-squared test as appropriate.  For the primary outcomes and 
all secondary outcomes, standard summary statistics comparing the two randomized groups will be 
provided by time of follow-up.   
 
Two primary intent-to-treat analyses will be performed to compare the MAO-B inhibitor and the placebo 
groups: one on the change of free-water accumulation in the SN for Aim 1 and the other on the change 
of BOLD signal in the posterior putamen for Aim 2. Linear regression will be conducted to estimate and 
test the group difference, adjusting pre-specified covariates age, gender, baseline UPDRS motor score 
and baseline free-water accumulation in the SN. To control overall type I error, each test will be at the 
two-tailed 0.025 significance level. For the primary intent-to-treat efficacy analysis, the missing primary 
outcome will be predicted by a fitted regression model using demographic and baseline clinical 
variables that characterize differences between “completers” and “non-completers.” In addition, we will 
perform sensitivity analysis by comparing analysis results based on the above imputation method with 
those from “complete-case” analysis and searching for a tipping point that reverses the study 
conclusion. Also, we will compare the two randomized groups in missing patterns in primary endpoint, 
including reasons for missing data, timing of missing data, and distributions of baseline covariates and 
earlier outcomes.  
 
For the secondary analysis, we will test the hypothesis that the MAO-B inhibitor will slow the 
progression of the BOLD signal in the M1 and SMA, using the same method as the primary analysis 
for the BOLD signal in the posterior contralateral putamen.  In addition, correlation analysis will be 
performed for secondary outcomes. We will evaluate if the change in free-water from the SN and the 
change in the BOLD signal from the posterior putamen relate to changes in the progression of the PD 
motor symptoms and bradykinesia. We will obtain confidence interval of correlation coefficients and 
perform hypothesis tests based on Fisher’s Z-transformation. No imputation is planned for secondary 
outcomes. Holm’s step-down procedure will be applied to adjust for multiple testing and determine 
statistical significance. 
 
 


 
 
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11. POSSIBLE DISCOMFORTS AND RISKS: 
If the subject has any metal in their eye or eyes (most likely the result of metalworking or an injury), we 
will require additional screening to ensure that it is safe for the subject to enter the magnetic resonance 
environment. These subjects will be sent to Radiology at Shands UF for an orbitofrontal x-ray. Shands 
will determine if it is safe for the subject to participate in this study. 
If the subject is a woman of childbearing potential, there may be unknown risks to the fetus. Therefore, 
before they can have the MRI, they must have a pregnancy test. An individual will not be allowed to 
participate if she is pregnant.  Nursing mothers are not eligible for participation in this project. The 
possibility exists that complications and undesirable side effects, which are unknown at this time, could 
occur. 
Individuals with any type of implanted electrical device (such as a cardiac pacemaker or a 
neurostimulator), or a certain type of metallic clip (i.e., an aneurysm clip in the brain), are not eligible 
for participation in this study. The magnet is very likely to cause malfunction of electrical devices, and 
metal objects will get hot with exposure to the magnetic fields. 
Aside from the above mentioned limitations of subject participation, there are no known significant risks 
with this procedure.  The radio waves and magnetic fields used by the MRI machine are thought to be 
without harm.  There are conservative Federal Guidelines for radio wave exposure and our 
examinations fall within those guidelines.  We feel these are safe levels. 
All metallic objects must be removed prior to approaching the high field strength magnet, as these 
objects may be attracted to the magnet.  In addition, such objects as watches and credit cards should 
also be removed as these could be damaged. 
Some subjects have experienced claustrophobia while inside the scanner.  This is a fear of enclosed 
spaces that can cause feelings of anxiety and physical symptoms which are characteristic of a 
heightened state of anxiety, such as increased heart rate, blood pressure, and body temperature.  
Subjects are advised that if they begin to feel claustrophobic, they may discontinue the scan at any 
time. 
The patients who go “off” their regular medications during the study may experience increased tremor 
(shaky hands), increased slowness and trouble walking.  In the “off” state, there is also an increased 
risk of falling.  In order to reduce the risk of injury, the patient will never drive, but be driven to the study 
by a spouse, by a family member or by a friend, who can assist them if they need help.  In the case 
that a friend or family member is unavailable, taxi transportation will be arranged to and from the UF 
laboratory.  Furthermore, patients who have difficulty walking off medication will be transported around 
the laboratory using a wheel chair.  Finally, if the patient has any problems while “off” their regular 
medications, laboratory staff will contact their physician. 
The risks of drawing blood from a vein include discomfort at the site of puncture; possible bruising and 
swelling around the puncture site; rarely an infection; and, uncommonly, faintness from the procedure. 
 
12.  POSSIBLE BENEFITS: 
 
There is no direct benefit to participating in this research.  Patients may learn more about their disease 
and learn more about how the body is affected by their disease. Future therapies and diagnoses may be 
improved upon by this knowledge. 
 


 
 
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13. CONFLICT OF INTEREST: 
 
The PI and collaborators do not have a conflict of interest. 
 
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Maruyama W, Boulton AA, Davis BA, Dostert P, Naoi M. Enantio-specific induction of apoptosis by an 
endogenous neurotoxin, N-methyl(R)salsolinol, in dopaminergic SH-SY5Y cells: suppression of apoptosis by N-(2-heptyl)-
N-methylpropargylamine. J Neural Transm 2001;108:11-24. 
63. 
Weinreb O, Bar-Am O, Amit T, Chillag-Talmor O, Youdim MB. Neuroprotection via pro-survival protein kinase 
C isoforms associated with Bcl-2 family members. FASEB J 2004;18:1471-1473. 
64. 
Blandini F, Armentero MT, Fancellu R, Blaugrund E, Nappi G. Neuroprotective effect of rasagiline in a rodent 
model of Parkinson's disease. Exp Neurol 2004;187:455-459. 
65. 
Zhu W, Xie W, Pan T, et al. Comparison of neuroprotective and neurorestorative capabilities of rasagiline and 
selegiline against lactacystin-induced nigrostriatal dopaminergic degeneration. Journal of neurochemistry 2008;105:1970-
1978. 
66. 
Sterling J, Veinberg A, Lerner D, et al. (R)(+)-N-propargyl-1-aminoindan (rasagiline) and derivatives: highly 
selective and potent inhibitors of monoamine oxidase B. J Neural Transm Suppl 1998;52:301-305. 
67. 
A controlled trial of rasagiline in early Parkinson disease: the TEMPO Study. Archives of neurology 2002;59:1937-
1943. 
68. 
A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease. Archives of neurology 
2004;61:561-566. 
69. 
Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a 
clinico-pathological study of 100 cases [see comments]. Journal of Neurology Neurosurgery and Psychiatry 1992;55:181-
184. 
70. 
Hughes AJ, Daniel SE, Lees AJ. Improved accuracy of clinical diagnosis of Lewy body Parkinson's disease. 
Neurology 2001;57:1497-1499. 
71. 
Nasreddine ZS, Phillips NA, Bedirian V, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool 
for mild cognitive impairment. J Am Geriatr Soc 2005;53:695-699. 
72. 
Vaillancourt DE, Prodoehl J, Sturman MM, Bakay RA, Metman LV, Corcos DM. Effects of deep brain stimulation 
and medication on strength, bradykinesia, and electromyographic patterns of the ankle joint in Parkinson's disease. Mov 
Disord 2006;21:50-58. 
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Vaillancourt DE, Prodoehl J, Verhagen Metman L, Bakay RA, Corcos DM. Effects of deep brain stimulation and 
medication on bradykinesia and muscle activation in Parkinson's disease. Brain 2004;127:491-504. 
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Yu H, Sternad D, Corcos DM, Vaillancourt DE. Role of hyperactive cerebellum and motor cortex in Parkinson's 
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in basal ganglia nuclei relates to specific symptoms in de novo Parkinson’s disease. Movement Disorders 2010;In Press. 
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Spraker MB, Prodoehl J, Corcos DM, Comella CL, Vaillancourt DE. Basal ganglia hypoactivity during grip force 
in drug naïve Parkinson’s disease. Human brain mapping 2010-In Press. 
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King JT, Jr., Tsevat J, Roberts MS. The physical performance test and the evaluation of functional status in patients 
with cerebral aneurysms. J Neurosurg 2006;104:525-530. 
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Buddenberg LA, Davis C. Test-retest reliability of the Purdue Pegboard Test. Am J Occup Ther 2000;54:555-558. 
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Vingerhoets FJ, Schulzer M, Calne DB, Snow BJ. Which clinical sign of Parkinson's disease best reflects the 
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ICF_001.pdf: 
IRB Project #: 201600537
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INFORMED CONSENT FORM
to Participate in Research, and
AUTHORIZATION 
to Collect, Use, and Disclose Protected Health Information (PHI)
INTRODUCTION
Name of person seeking your consent:
Place of employment & position: 
Please read this form which describes the study in some detail. A member of the research 
team will describe this study to you and answer all of your questions.  Your participation is 
entirely voluntary.  If you choose to participate you can change your mind at any time and 
withdraw from the study.  You will not be penalized in any way or lose any benefits to which 
you would otherwise be entitled if you choose not to participate in this study or to withdraw.  
If you have questions about your rights as a research subject, please call the University of 
Florida Institutional Review Board (IRB) office at (352) 273-9600.   
GENERAL INFORMATION ABOUT THIS STUDY
1.
Name of Participant ("Study Subject")
___________________________________________________________________ 
2.
What is the Title of this research study?
Image Parkinson’s Disease Progression Study
3.
Who do you call if you have questions about this research study?
Principal Investigator: David Vaillancourt, Ph.D. Phone: 773-307-8352
4.   Who is paying for this research study? 
The sponsor of this study is the National Institutes of Health.
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5. In general, what do you need to know about this Research Study? 
Agreeing to become involved in any research is always voluntary.  By signing this 
form, you are not waiving any of your legal rights.  If you decide not to participate in 
this research, you will not be penalized in any way and you will not lose any benefits 
to which you are entitled. If you have questions about your rights as a research 
subject, please call the University of Florida Institutional Review Board (IRB) office at 
(352) 273-9600.    
a) In general, what is the purpose of the research, how long will you be 
involved?    
The purpose of this research study is to investigate how the brain and motor 
behavior changes Parkinson’s disease over time in response to rasagiline and to 
investigate new methods of evaluating non-invasive MRI-based biomarkers of 
PD progression in the brain. The drug rasagiline will be tested in this study. 
Rasagiline has been prescribed by doctors for many years to treat symptomatic 
Parkinson’s disease. It is FDA approved for the treatment of Parkinson’s disease 
but has not been shown to slow disease progression. You are being asked to be 
in this research study because you meet our criteria for individuals with PD. 
Clinical assessments will also be performed to help determine whether you are 
eligible for the study. The study staff will discuss these requirements with you. A 
description of this clinical trial will be available on http://www.ClinicalTrials.gov, 
as required by U.S. Law. This Web site will not include information that can 
identify you. At most, the Web site will include a summary of the results. You can 
search this Website at any time.
You will be asked to come to the researcher’s lab at the University of Florida for 
2 testing days within a period of about 12 months. You will be tested at your 
initial visit, and once following one year. We will contact you after 3, 6, and 9 
months to assess any changes in your medical status, provide study medication 
reminders, and mail you medication or placebo pills. You will not be asked to 
answer any questionnaires or perform any additional assessments during these 
follow-up calls. We may ask to extend your study medication or delay your one 
year follow up visit, due to scheduling conflicts or unforeseeable circumstances.
At both visits you will be tested in an “off” medication condition. You will be 
asked to refrain from taking any of the medications used to control your 
movement disorder after 6:00 p.m. on the night before the study visit. This 
includes the medication or placebo pill given to you through this study as well as 
any additional medications taken to control your movement disorder. At the 
conclusion of the study, you may request to find out which treatment you 
received: either the placebo or the study medication, rasagiline. If you do not 
request to obtain this information, you will not receive this information.
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b) What is involved with your participation, and what are the procedures to be 
followed in the research? 
During the experiment, you will be asked to complete the following: (1) 
questionnaires about quality of life, depression, anxiety, and apathy; (2) tests to 
measure your strength and motor function; (3) tests to measure your cognition; 
(4) orientation session to learn a precision gripping task; (5) functional MRI scan 
of your brain; (6) structural MRI scan of your brain; (7) pregnancy test (if 
applicable); (8) tests to measure sleeping behaviors (9) at the follow up visit – 
questionnaires about any adverse or serious adverse events.
c) What are the likely risks or discomforts to you? 
Rasagiline is FDA approved to treat Parkinson’s disease symptoms, and is a 
widely used medication, but it has not been proven to slow the progression of 
Parkinson’s disease. You should not take rasagiline if you have certain medical 
conditions or are taking certain medications.  If you could be pregnant, you should 
not participate in this study
d) What are the likely benefits to you or to others from the research? 
The benefit to you from being in this study may be a slowing of the progression of 
Parkinson’s disease during the study. The study drug will not be provided to you 
once your participation in the study has ended.   
e) What are the appropriate alternative procedures or courses of treatment, if 
any, that might be helpful to you?  
This study involves using a drug (rasagiline) to see if it slows progression of
Parkinson’s disease. You are free to seek clinical care in the same way whether or
not you participate in the study.
Additional and more detailed information is provided within the remainder of this 
Informed Consent form, please read before deciding if you wish to participate in this 
study.
WHAT CAN YOU EXPECT IF YOU PARTICIPATE IN THIS STUDY?
6.   What will be done as part of your normal clinical care (even if you did not 
participate in this research study)? 
This study involves using a drug (rasagiline) to see if it slows progression of 
Parkinson’s disease. You are free to seek clinical care in the same way whether or 
not you participate in the study. Your normal clinical care will be followed.
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7.   What will be done only because you are in this research study? 
Half of the participants in this study will be in a group that will receive the study drug 
(rasagiline), and half will be in a group that will receive a placebo. A placebo is a pill 
that is made to look like the study drug, but it does not contain any active ingredients. 
A computer algorithm will randomly decide your group assignment (like the flip of a 
coin). You will not be told which group you are in. If you are not willing to be in the 
placebo group, you should not participate in this study. The study staff will not know 
which group you are in until the study is over. If you develop a medical problem during 
the study and a doctor needs to know whether you are taking the study drug or the 
placebo, that information will be made available to the doctor. The study staff will 
provide you with instructions so that your doctor can request this information, if 
necessary.
Either rasagiline or placebo will be given to you at the completion of the first visit. You 
will take the drug or placebo every day for duration of the study, which is one year. 
The study staff will review with you how often to take the drug each day, which is one 
pill per day.
You will be asked to come to the researcher’s lab at the University of Florida for 2 
testing days within a period of about 12 months. You will be tested at your initial visit, 
and once following one year. We will contact you after 3, 6, and 9 months to assess 
any changes in your medical status, provide study medication reminders, and mail 
you medication or placebo pills. You will not be asked to answer any questionnaires 
or perform any additional assessments during these follow-up calls. We may ask to 
extend your study medication or delay your one year follow up visit, due to scheduling 
conflicts or unforeseeable circumstances.
At both visits you will be tested in an “off” medication condition. You will be asked to 
refrain from taking any of the medications used to control your movement disorder 
after 6:00 p.m. on the night before the study visit. This includes the medication or 
placebo pill given to you through this study as well as any additional medications 
taken to control your movement disorder. 
At the conclusion of the study, you may request to find out which treatment you 
received: either the placebo or the study medication, rasagiline. If you do not request 
to obtain this information, you will not receive this information. 
Orbitofrontal X-ray 
If you have a history of metal in your eye or eyes, the researchers will require 
additional screening to ensure that it is safe for you to enter the magnetic resonance 
environment. The researchers may refer you to Radiology at Shands UF for an 
orbitofrontal x-ray. Shands at UF will provide a written report stating whether you are 
safe for imaging in this study. All expenses related to this procedure will be covered 
by the National Institutes of Health.
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Orientation session 
We will explain the study to you, review the informed consent document and answer 
questions you may have about the study. If you agree to participate in this research, 
we will begin gathering data. At the one-year follow-up visit, the study and the 
informed consent document will be reviewed with you once more, and you will again 
have the opportunity to ask questions about the study.
Clinical Measures 
We will gather data about your age, gender, height, weight and medical conditions. 
You will be asked to complete forms that test your neurological status like the Unified 
Parkinson’s disease rating scale where we will rate your performance on tasks like 
tapping your fingers and tapping your heels. With your permission, this rating scale 
will be video recorded to ensure rating reliability. You will be asked to take tests that 
assess your cognitive abilities, emotional status and quality of life. The cognitive tests 
will measure aspects like comprehension, memory and attention span. The emotional 
status tests will assess your current level of depression, anxiety, and apathy. The 
quality of life tests will assess how your movement disorder affects your daily life. 
Assessments regarding sleep behaviors will measure sleepiness and rapid eye 
movement behaviors. If you do not wish to complete all of the questions in the tests 
mentioned above, you are able to skip questions with no penalty. At your follow-up 
visit, we will also gather information about any adverse events that might have 
occurred throughout the duration of your participation in the study. 
Measurement of brain structure and brain function 
This experiment will require you to lie down on a platform that will move into an 
enclosed functional Magnetic Resonance Imaging scanner (fMRI). fMRI is a 
technique used to non-invasively measure changes in brain activity in relation to 
performance of a specific task. In brain structure measures, you will lie still in the MRI 
without performing a task. In brain function measures, you will perform a task. You will 
be asked to practice the experimental tasks described below until you feel 
comfortable performing them. During this task you will use a small pinch grip device 
that you will hold between the thumb and index finger. Once inside the scanner, you 
will be asked to lie still while we perform a scan, which will provide us with an 
anatomical picture of your brain. You will be asked to complete a series of tasks 
during which we will obtain pictures of the functional changes in brain activity. During 
this task you will move your hand under different conditions. In one condition you will 
be asked to perform the task with no sensory information about the task. We will refer 
to this as a “self-initiated” task. No stimulus will be presented in this condition. In 
another condition you will be asked to respond to a stimulus, which will give you 
information regarding the timing of your movement or the extent to which you should 
contract your muscles. We will refer to this as an “auditory cued task” or a “visually 
cued task”. Your goal during all movement conditions will be to move as quickly as 
possible. If you would like a copy of the images collected during this scan, a disc 
containing the images will be provided for you at your request. You will not receive 
any clinical feedback regarding your scan. 
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Physical performance measures 
You will be asked to perform different physical tests that will measure your ability to 
perform daily activities. You may be asked to perform a test that will measure your 
ability to perform everyday tasks like picking up a penny off the floor, a test that will 
measure how well you can tolerate walking at various speeds and climbing stairs, a 
test that will measure your ability to work with your hands and a test that will measure 
your balance and risk for falling. In addition, you will be asked to do a test of handgrip 
strength. 
If you have any questions now or at any time during the study, please contact one of 
the research team members listed in question 3 of this form. By agreeing to 
participate in this study, you are agreeing to complete all checked items in one 24 
hour period. If you choose to complete the study over several days, you will be re-
consented at each visit with a check only on the items to be completed that day.

Medical history (~10 minutes) 

Orientation session to learn a precision gripping task (~30 minutes) 

Questionnaires about depression (~5 minutes) 

Tests to measure your quality of life and health status (~40 minutes) 

Tests to measure your strength and motor function (~20 minutes) 

Tests to measure your cognition (mental capabilities) (~40 minutes) 

Functional MRI scan of your brain (~30 minutes) 

Structural MRI scan of your brain (~30 minutes) 
Tests done only for research purposes will not be evaluated or used to diagnose or 
treat any of your medical problems. This/these test(s) may need to be repeated if 
required for your medical care in the future.
Once this research study is completed, any information that could identify you might
be removed from any identifiable private information or identifiable biospecimens 
collected and that, after such removal, the information or biospecimens could be used 
for future research studies or distributed to another investigator for future research 
studies without additional informed consent from you or your legally authorized 
representative
If you have any questions now or at any time during the study, please contact one of 
the research team members listed in question 3 of this form.
8.
How long will you be in this research study?
You will be asked to come to the researcher’s lab at the University of Florida for 2 
testing sessions within a period of about 12 months. You will be tested at your initial 
visit and following one year. Each session may last up to eight hours. Between each 
of the 2 visits, you will take either a placebo pill or the study medication, rasagiline, 
once per day and receive follow-up calls after 3, 6, and 9 months to assess any 
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changes in your medical status, provide study medication reminders, and mail you 
medication or placebo pills.
9.
How many people are expected to take part in this research study?
We expect that up to 200 people will take part in this research study.
WHAT ARE THE RISKS AND BENEFITS OF THIS STUDY AND 
WHAT ARE YOUR OPTIONS?
10. What are the possible discomforts and risks from taking part in this research 
study?
This study might involve the following risks and discomforts to you:

Rasagiline. Rasagiline is FDA approved to treat Parkinson’s disease 
symptoms, and is a widely used medication, but it has not been proven to slow 
the progression of Parkinson’s disease. You should not take rasagiline if you 
have certain medical conditions or are taking certain medications. The study 
staff will discuss these with you. Most side effects of rasagiline are mild and 
short lived. Reported side effects of rasagiline include joint pain, mild 
headache, depressed mood, dizziness, drowsiness, hair loss, mild skin rash, 
numbness or tingling, dry mouth, decreased appetite, constipation, diarrhea, 
upset stomach or abdominal pain, heartburn, nausea/vomiting, and weight 
loss. 

Placebo. There is no anticipated risk from placebo, as it contains no active 
ingredient. 

If you could be pregnant, you should not participate in this study. The use of 
fMRI scanning on the developing fetus is not known. Therefore, women must 
be taking an approved form of birth control, be surgically sterile, or 
postmenopausal. In order to participate in this study, you should have avoided 
becoming pregnant from the first day of your most recent menses. A negative 
pregnancy test does not absolutely prove that you are not pregnant. You 
should not participate if you think there is a possibility that you might be 
pregnant. If prior to your participation in this study you think you have become 
pregnant, you must immediately notify the study investigator, David 
Vaillancourt. Nursing mothers are not eligible for participation in this project. 
The possibility exists that complications and undesirable side effects, which 
are unknown at this time, could occur. You will be informed of any significant 
new findings that may affect your willingness to continue participation in this 
study. 

If you have some type of implanted electrical device (such as a cardiac 
pacemaker or a neurostimulator), or a certain type of metallic clip in your body 
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(i.e., an aneurysm clip in your brain), you are not eligible for participation in the 
MRI portion of the study. The magnet is very likely to cause malfunction of 
electrical devices, and metal objects will get hot with exposure to the magnetic 
fields. 

If you have any metal in your eye or eyes, the researchers will require 
additional screening to ensure that it is safe for you to enter the magnetic 
resonance environment. It is very important to report any history of 
metalworking, especially metalworking involving cutting processes such as 
grinding, filing, shaving, and threading. In addition, please report any previous 
injuries or surgeries involving your eyes. For your safety, the researchers may 
refer you to Radiology at Shands UF for an orbitofrontal xray. Shands at UF 
will provide a written report stating whether you are safe for imaging in this 
study. All expenses related to this procedure will be covered by the National 
Institutes of Health. 

Please take note that some subjects have experienced claustrophobia while 
inside the scanner. If you begin to feel claustrophobic, you may discontinue the 
scan at any time. Many people who do experience claustrophobia feel the 
anxiety immediately after being put inside the scanner. If that is the case, we 
can take you out before the data collection has begun and the experiment will 
be cancelled. If you experience a delayed reaction after the experiment has 
begun, there is a speaker in the scanning room through which we can hear 
you speak. Speak out and we will come in and have you out of the scanner 
within 1-2 minutes. 

This research study may involve exposure to radiation from either a skull or 
orbital x-ray. The radiation exposure from one of these x-rays is approximately 
42 millirems, which is comparable to about 7 extra weeks of natural 
background radiation to which people in the United States are exposed to 
during their lives. The risk from this radiation exposure is considered to be 
extremely low when compared to other every day risks. The study doctor will 
provide you with a contact person if you would like more information about 
radiation exposure. 
If the anxiety and depression questionnaires reveal that you have feelings of harming 
yourself related to depression, we will refer you to mental health services available at 
Shands at the University of Florida. 
Aside from the above-mentioned limitations of subject participation, there are no 
known significant risks with this procedure. The radio waves and magnetic fields used 
by the MRI machine are thought to be without harm. There are conservative Federal 
Guidelines for radio wave exposure and our examinations fall within those guidelines. 
We feel these are safe levels. 
Again, the exception is if you have a cardiac pacemaker, neurostimulator, or a certain 
type of metallic clip in your body (i.e., an aneurysm clip in your brain). 
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It is important that all metallic objects be removed from your person prior to 
approaching the high field strength magnet, as these objects may be attracted to the 
magnet. In addition, such objects as watches and credit cards should also be 
removed as these could be damaged. (These items will be locked up for you.) 
When you go “off” your regular PD medications during the study, you may experience 
increased tremor (shaky hands), increased slowness and trouble walking. In the “off” 
state, there is also an increased risk of falling. In order to reduce the risk of injury, you 
will never drive, but be driven to the study by a spouse, by a family member or by a 
friend who can assist you if you need help. In the case that a friend or family member 
is unavailable, taxi transportation will be arranged to and from the UF or FSU 
laboratory. Furthermore, if you have difficulty walking off medication, you will be 
transported around the laboratory using a wheel chair. Finally, if you have any 
problems while “off” you regular medications, laboratory staff will contact your 
physician. At home, we suggest that you are always accompanied by a spouse, 
family member or friend in the “off” state.
Researchers will take appropriate steps to protect any information they collect about 
you.  However, there is a slight risk that information about you could be revealed 
inappropriately or accidentally.  Depending on the nature of the information, such a 
release could upset or embarrass you, or possibly affect your insurability or 
employability.  Questions 17-21 in this form discuss what information about you will 
be collected, used, protected, and shared.
This study may include risks that are unknown at this time.
Participation in more than one research study or project may further increase the risks 
to you.  If you are already enrolled in another research study, please inform one of the 
research team members listed in question 3 of this form or the person reviewing this 
consent with you before enrolling in this or any other research study or project.
Throughout the study, the researchers will notify you of new information that may 
become available and might affect your decision to remain in the study. 
If you wish to discuss the information above or any discomforts you may experience, 
please ask questions now or call one of the research team members listed in question 
3 in this form.
11a. What are the potential benefits to you for taking part in this research study?
The benefit to you from being in this study may be a slowing of the progression of 
Parkinson’s disease during the study. The study drug will not be provided to you once 
your participation in the study has ended.
11b. How could others possibly benefit from this study?
Others may benefit from our increased understanding of how the body works. Future 
therapies and diagnoses may be improved upon by this knowledge.
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11c. How could the researchers benefit from this study?
In general, presenting research results helps the career of a scientist. Therefore, the 
Principal Investigator listed in question 3 of this form may benefit if the results of this 
study are presented at scientific meetings or in scientific journals.
12. What other choices do you have if you do not want to be in this study? 
The option to taking part in this study is doing nothing. If you do not want to take part, 
tell the Principal Investigator or his/her assistant and do not sign this Informed 
Consent Form.
13a. Can you withdraw from this study?
You are free to withdraw your consent and to stop participating in this study at any 
time.  If you do withdraw your consent, you will not be penalized in any way and you 
will not lose any benefits to which you are entitled.  If you decide to withdraw your 
consent to participate in this study for any reason, please contact one of the research 
team members listed in question 3 of this form.  They will tell you how to stop your 
participation safely.
If you have any questions regarding your rights as a research subject, please call the 
Institutional Review Board (IRB) office at (352) 273-9600.
13b.If you withdraw, can information about you still be used and/or collected?
If you withdraw from this study, the Principal Investigator would like to use any 
information about you that has already been collected. No further data will be 
collected. 
13c. Can the Principal Investigator withdraw you from this study? 
You may be withdrawn from the study without your consent for the following reasons:

because you have had an unexpected reaction

or have failed to follow instructions

or because you are found not to meet eligibility criteria

or because the study has been stopped.

Also, if the investigator feels that continuing in the study could be too risky for 
you or could cause problems for the study, you could be withdrawn from the 
study.
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WHAT ARE THE FINANCIAL ISSUES IF YOU PARTICIPATE?
14. If you choose to take part in this research study, will it cost you anything?
Study Drugs 
Rasagiline or placebo will be provided at no cost to you while you are participating in 
this study. 
Study Services 
The Sponsor will pay for or provide all medical services and activities required as part 
of your participation in this study as described above in the question “What Will Be 
Done Only Because You Are In This Research Study”. If you receive a bill related to 
this study, please contact David Vaillancourt, Ph.D. at 773-307-8352. 
Items/Services Not Paid for by the Sponsor 
Any other medical services you receive would have been provided to you even if you 
were not in this study. These services will be billed to you or your insurance company 
in the usual manner. You will be responsible for paying any deductible, co-insurance, 
co-payments, for those services, and for any non-covered or out-of-network services. 
15. Will you be paid for taking part in this study?
You will receive $100.00 for each visit to the laboratory. If you are traveling to the 
Gainesville (University of Florida) area from more than 50 miles away, your 
transportation costs to and from the testing site and additional meal costs will be 
reimbursed. Finally, during long testing sessions, food and beverages for you and any 
family members and/or caregivers that accompany you to the visit will be provided at 
no expense to you. 
If you are paid more than $75 for taking part in this study, your name and social 
security number will be reported to the appropriate University employees for purposes 
of making and recording the payment as required by law. You are responsible for 
paying income taxes on any payments provided by the study. If the payments total 
$600 or more or you are a nonresident alien, payment will be processed through the 
University of Florida Accounts Payable department and the University must report the 
amount you received to the Internal Revenue Service (IRS). The IRS is not provided 
with the study name or its purpose. If you have questions about the collection and use 
of your Social Security Number, please visit: http://privacy.ufl.edu/SSNPrivacy.html. 
Your payment for participation in this research study is handled through the University 
of Florida’s Human Subject Payment (HSP) Program. Your information which will 
include your name, address, date of birth, and SSN (depending on amount of money 
you are paid) is protected. 
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Access to the (HSP) Program site is limited to certain staff with the assigned security 
role. You will be randomly assigned a specific identification (ID) number to protect 
your identity. 
The study team will provide you with an informational form called the Prepaid Card 
Facts document. If you have any problems regarding your payment call the HSP 
Office (352) 392-9057. 
16. What if you are injured because of the study?   
If you are injured as a direct result of your participation in this study, only the 
professional services that you receive from any University of Florida Health Science 
Center healthcare provider will be provided without charge.  These healthcare 
providers include physicians, physician assistants, nurse practitioners, dentists or 
psychologists. Any other expenses, including Shands hospital expenses, will be billed 
to you or your insurance provider. 
You will be responsible for any deductible, co-insurance, or co-payments. Some 
insurance companies may not cover costs associated with research studies or 
research-related injuries. Please contact your insurance company for additional 
information. 
The Principal Investigator will determine whether your injury is related to your 
participation in this study. 
No additional compensation is routinely offered. The Principal Investigator and others 
involved in this study may be University of Florida employees. As employees of the 
University, they are protected under state law, which limits financial recovery for 
negligence.
Please contact one of the research team members listed in question 3 of this form if 
you experience an injury or have questions about any discomforts that you 
experience while participating in this study.
17. How will your health information be collected, used and shared?
If you agree to participate in this study, the Principal Investigator will create, collect, 
and use private information about you and your health. This information is called 
protected health information or PHI. In order to do this, the Principal Investigator 
needs your authorization  The following section describes what PHI will be collected, 
used and shared, how it will be collected, used, and shared, who will collect, use or 
share it, who will have access to it, how it will be secured, and what your rights are to 
revoke this authorization. 
Your protected health information may be collected, used, and shared with others to 
determine if you can participate in the study, and then as part of your participation in 
the study.  
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This information can be gathered from you or your past, current or future health 
records, from procedures such as physical examinations, x-rays, blood or urine tests 
or from other procedures or tests.  
This information will be created by receiving study treatments or participating in study 
procedures, or from your study visits and telephone calls.  More specifically, the 
following information may be collected, used, and shared with others: 

General medical history including age, gender, height, weight, medications and 
other medical conditions 

Your name, your medical record number, your contact information, and dates 
associated with treatments and tests that are relevant to this research study 

Your social security number for compensation purposes 

Anatomical and functional scans of your brain 

Measures of cognitive and motor function as well as quality of life as it relates 
to PD 

Pregnancy tests  
This information will be stored in locked filing cabinets or on computer servers with 
secure passwords, or encrypted electronic storage devices. 
Some of the information collected could be included in a "limited data set" to be used 
for other research purposes.  If so, the limited data set will only include information 
that does not directly identify you.  For example, the limited data set cannot include 
your name, address, telephone number, social security number, photographs, or 
other codes that link you to the information in the limited data set.  If limited data sets 
are created and used, agreements between the parties creating and receiving the 
limited data set are required in order to protect your identity and confidentiality and 
privacy.
18. For what study-related purposes will your protected health information be 
collected, used, and shared with others?
Your PHI may be collected, used, and shared with others to make sure you can 
participate in the research, through your participation in the research, and to evaluate 
the results of the research study.  More specifically, your PHI may be collected, used, 
and shared with others for the following study-related purpose(s):

To gain a better understanding of the effects of Rasagiline on the brain and 
motor behavior 

To help develop ways to improve neurological rehabilitation programs and 
medications
Once this information is collected, it becomes part of the research record for this 
study.  
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19. Who will be allowed to collect, use, and share your protected health 
information?
Only certain people have the legal right to collect, use and share your research 
records, and they will protect the privacy and security of these records to the extent 
the law allows. These people include:

the study Principal Investigator (listed in question 3 of this form) and research 
staff associated with this project.

other professionals at the University of Florida or Shands Hospital that provide 
study-related treatment or procedures.

the University of Florida Institutional Review Board (IRB; an IRB is a group of 
people who are responsible for looking after the rights and welfare of people 
taking part in research).  
20. Once collected or used, who may your protected health information be shared 
with?
Your PHI may be shared with:

the study sponsor (listed in Question 4 of this form).

United State and foreign governmental agencies who are responsible for 
overseeing research, such as the Food and Drug Administration, the 
Department of Health and Human Services, and the Office of Human Research 
Protections
.

Government agencies who are responsible for overseeing public health 
concerns such as the Centers for Disease Control and federal, state and local 
health departments.

North Florida/South Georgia VHS 

Your insurance company for purposes of obtaining payment 
Otherwise, your research records will not be released without your permission unless 
required by law or a court order. It is possible that once this information is shared with 
authorized persons, it could be shared by the persons or agencies who receive it and 
it would no longer be protected by the federal medical privacy law.  
21. If you agree to take part in this research study, how long will your protected 
health information be used and shared with others?
Your PHI will be used and shared with others until the end of the study. Some 
information will be used and disclosed for an indefinite period of time since it will be 
stored in a coded format in a secure database.
You are not required to sign this consent and authorization or allow researchers to 
collect, use and share your PHI. Your refusal to sign will not affect your treatment, 
payment, enrollment, or eligibility for any benefits outside this research study. 
However, you cannot participate in this research unless you allow the collection, use 
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and sharing of your protected health information by signing this consent and 
authorization.
You have the right to review and copy your protected health information.  However, 
we can make this available only after the study is finished.
You can revoke your authorization at any time before, during, or after your 
participation in this study.  If you revoke it, no new information will be collected about 
you.  However, information that was already collected may still be used and shared 
with others if the researchers have relied on it to complete the research.  You can 
revoke your authorization by giving a written request with your signature on it to the 
Principal Investigator.
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SIGNATURES
As an investigator or the investigator’s representative, I have explained to the participant 
the purpose, the procedures, the possible benefits, and the risks of this research study; 
the alternative to being in the study; and how the participant’s protected health 
information will be collected, used, and shared with others: 
Signature of Person Obtaining Consent and 
Authorization
Date
You have been informed about this study’s purpose, procedures, possible benefits, and 
risks; the alternatives to being in the study; and how your protected health information will 
be collected, used and shared with others.  You have received a copy of this Form.  You 
have been given the opportunity to ask questions before you sign, and you have been told 
that you can ask   questions at any time.  
You voluntarily agree to participate in this study. You hereby authorize the collection, use 
and sharing of your protected health information as described in sections 17-21 above.  By 
signing this form, you are not waiving any of your legal rights.
Signature of Person Consenting and Authorizing
Date
 
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Consent to be Photographed, Video and/or Audio Recorded
With your permission, you will have the following done during this research (check all 
that apply):
 photographed
 video recorded
 audio recorded
Your name or personal information will not be identified on the photograph(s), video or 
audio recordings, and confidentiality will be strictly maintained.  However, when these 
photograph(s), video and/ or audio recordings are shown or heard, others may be able 
to identify you.
The Principal Investigator (PI) of this study, Dr. David Vaillancourt, or his successor, will 
keep the photograph(s), video and/or audio recordings in a locked cabinet, in a folder on 
a password protected computer server drive, or as an encrypted electronic file.  These 
photograph(s), video and/or audio recordings will be shown under his direction to 
students, researchers, doctors, or other professionals and persons.
Please indicate under what conditions Dr. David Vaillancourt has your permission to use 
the photograph(s), video and/or audio recordings, and sign and date below.
  The following will be destroyed once the study is closed (initial next to all that 
apply):   
  ____ photograph(s)      _____ video recording(s)        _____ audio recording(s)
  As described in the Informed Consent Form, and for the purposes of education 
at the University of Florida Health Science Center.  The PI may keep the 
following for an indefinite period of time in a locked file, in a password protected 
computer server drive, or as an encrypted electronic file (initial next to all that 
apply):      
  ____ photograph(s)      _____ video recording(s)        _____ audio recording(s)
  As described in the Informed Consent Form; for the purposes of education at 
the University of Florida Health Science Center; and for presentations at 
scientific meetings outside the University.  The PI may keep the following for 
an indefinite period of time in a locked file, in a password protected computer 
server drive, or as an encrypted electronic file (initial next to all that apply):
  ____ photograph(s)      _____ video recording(s)        _____ audio recording(s)
Signature
Date
                                                                                                                          
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