Clinical trial NCT05487300
Conditions: Parkinson Disease Orthostatic Hypotension
Sponsor: University of Utah
Start date: 2022-05-11; Completion date: 2023-05-01
Enrollment: 40 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
Levodopa is a precursor of dopamine and is the treatment of choice to treat the motor symptoms of Parkinson's disease (PD); however, the effect of levodopa on cardiovascular autonomic function in PD is poorly understood. Orthostatic hypotension has been documented as a potential side effect of levodopa. As a result, clinicians may be reluctant to prescribe levodopa in patients with PD with neurogenic orthostatic hypotension (PD+OH), which leads to suboptimal management of motor symptoms. On the other hand, other studies failed to show any clear relationship between levodopa and orthostatic hypotension in patients with PD. Important limitations of prior studies include the lack of detailed investigation of baroreflex cardiovagal and sympathetic noradrenergic functions and the fact that the same patients were not tested on and off levodopa.

The investigators propose to investigate the effects of levodopa on cardiovascular autonomic function in patients with PD+OH and PD without neurogenic orthostatic hypotension (PD-OH) by performing standardized autonomic testing in the same patients on and off levodopa.

Detailed description:
Parkinson's disease (PD) is characterized by the gradual onset of motor symptoms such as bradykinesia, rigidity, tremor, gait difficulties and postural instability, as well as non-motor symptoms such as cognitive impairment and autonomic dysfunction among others. Neurogenic orthostatic hypotension (nOH) is the main clinical manifestation of cardiovascular autonomic dysfunction. The arterial baroreflex allows for beat-to-beat regulation of the blood pressure and heart rate via differential modulation of its cardiovagal (parasympathetic) and noradrenergic (sympathetic) efferent limbs. Several mechanisms may contribute to nOH in PD including baroreflex-cardiovagal and baroreflex-sympathetic noradrenergic failure. The prevalence of nOH in PD increases with age and disease duration; however, several studies have documented that nOH may appear early in the course of PD and reported prevalence of nOH in PD ranges from 30% to 65%. The presence of nOH in PD is associated with poor outcomes related to cardiovascular events, increased morbidity and mortality, more rapid disease progression, cognitive impairment, and falls.

Levodopa is a precursor of dopamine and is the treatment of choice to treat the motor symptoms of PD; however, the effect of levodopa on cardiovascular autonomic function in PD is poorly understood. Orthostatic hypotension has been documented as a potential side effect of levodopa in different studies. As a result, clinicians may be reluctant to prescribe levodopa in patients with PD with nOH (PD+OH), which leads to suboptimal management of motor symptoms. On the other hand, several studies failed to show any clear relationship between levodopa and orthostatic hypotension in patients with PD. Important limitations of prior studies include the lack of detailed investigation of baroreflex cardiovagal and sympathetic noradrenergic functions and the fact that the same patients were not tested on and off levodopa.

The investigators propose to investigate the effects of levodopa on cardiovascular autonomic function in patients with PD+OH and PD without nOH (PD-OH) by performing standardized autonomic testing in the same patients on and off levodopa.

Clinical assessment: We will perform a medical history and physical examination before the testing procedures (baseline visit). The baseline visit will be performed on levodopa. The scales and assessments will include the Composite Autonomic Symptoms Score 31 (COMPASS 31), the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part I, II, III, and Hoehn and Yahr stage. The clinical assessment and scales are part of the standard of care in PD. Orthostatic vital signs will active standing will be also performed the two days of autonomic testing.

Participants will undergo a baseline visit. During the baseline visit, investigators will perform a medical history and physical examination and complete the following scales: Composite Autonomic Symptoms Score 31 (COMPASS 31), the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part I, II, III, and Hoehn and Yahr. Participants will undergo autonomic testing on two separate days. The first autonomic testing will occur within 4 weeks of the baseline visit. The two autonomic tests will occur within a 2-week timeframe. To avoid any confounding of treatment effects and period effects, the order of testing (on versus off levodopa) will be randomized so testing on the first day will be on-levodopa for half of the participants and off-levodopa for the other participants. Autonomic testing will include assessment of heart rate and blood pressures responses during the Valsalva maneuver and a 10-minute tilt table test.

Arms: arm 1: Participants underwent autonomic testing one hour after taking their regular morning dose of levodopa (ON state). On a separate day, they then underwent autonomic testing after at least 12 hours from the last dose of levodopa (OFF state). arm 2: Participants underwent autonomic testing after at least 12 hours from the last dose of levodopa (OFF state). On a separate day, they then underwent autonomic testing one hour after taking their regular morning dose of levodopa (ON state).
Interventions: intervention 1: Autonomic testing on and off levodopa
Intervention descriptions: intervention 1: Participants with Parkinson's disease with and without orthostatic hypotension will undergo standardized autonomic testing on two separate days "on levodopa" and "off levodopa".

Protocol documents:
Prot_SAP_001.pdf: 
Protocol Summary (ERICA) 
IRB_00152581 
Page 1 of 9 
IRB Approval 4/10/2023 
Effect of levodopa on cardiovascular autonomic function 
in Parkinson’s disease with and without orthostatic 
hypotension: a cross-over study 
NCT number: 05487300 
Document date: 10/10/2024 


 
Protocol Summary (ERICA) 
 
IRB_00152581 
Page 2 of 9 
 
IRB Approval 4/10/2023 
 
Protocol Summary 
 
 
 
IRB Approval 
Date of 
Current 
Version: 
4/10/2023 
University of 
Utah IRB #: 
IRB_00152581 
Sponsor: UNIVERSITY OF UTAH RESEARCH FOUNDATION 
  
Principal 
Investigator: 
Guillaume Lamotte 
Internal Staff 
and  Sub-
Investigators: 
Site Name 
Staff Names 
University of Utah 
Principal 
Investigator 
Guillaume Lamotte 
 
This document was created using the ERICA Online System at the University of Utah. The document is created 
from study information approved by the IRB on the date listed above.  Any alteration to the original content of this 
document may not be considered to represent the study as approved by the IRB.  
 
 


 
Protocol Summary (ERICA) 
 
IRB_00152581 
Page 3 of 9 
 
IRB Approval 4/10/2023 
 
Background and Introduction 
 
Parkinson’s disease (PD) is characterized by the gradual onset of motor symptoms such as 
bradykinesia, rigidity, tremor, gait difficulties and postural instability, as well as non-motor 
symptoms such as cognitive impairment and autonomic dysfunction among others [1]. 
Neurogenic orthostatic hypotension (nOH) is the main clinical manifestation of cardiovascular 
autonomic dysfunction [2]. The arterial baroreflex allows for beat-to- beat regulation of the 
blood pressure and heart rate via differential modulation of its cardiovagal (parasympathetic) 
and noradrenergic (sympathetic) efferent limbs [3]. Several mechanisms may contribute to 
nOH in PD including baroreflex-cardiovagal and baroreflex-sympathetic noradrenergic failure 
[2]. The prevalence of nOH in PD increases with age and disease duration; however, several 
studies have documented that nOH may appear early in the course of PD and reported 
prevalence of nOH in PD ranges from 30% to 65% [4, 5]. The presence of nOH in PD is 
associated with poor outcomes related to cardiovascular events, increased morbidity and 
mortality, more rapid disease progression, cognitive impairment, and falls [6]. 
  
Levodopa is a precursor of dopamine and is the treatment of choice to treat the motor 
symptoms of PD; however, the effect of levodopa on cardiovascular autonomic function in PD 
is poorly understood. Orthostatic hypotension has been documented as a potential side effect 
of levodopa in different studies [7, 8]. As a result, clinicians may be reluctant to prescribe 
levodopa in patients with PD with nOH (PD+OH), which leads to suboptimal management of 
motor symptoms. On the other hand, several studies failed to show any clear relationship 
between levodopa and orthostatic hypotension in patients with PD [9-12]. Important 
limitations of prior studies include the lack of detailed investigation of baroreflex cardiovagal 
and sympathetic noradrenergic functions and the fact that the same patients were not tested on 
and off levodopa. 
We propose to investigate the effects of levodopa on cardiovascular autonomic function in 
patients with PD+OH and PD without nOH (PD-OH) by performing standardized autonomic 
testing in the same patients on and off levodopa. 
  
References: 
1. Kalia LV, Lang AE. Parkinson's disease. Lancet (London, England) 2015;386:896-912. 
2. Pfeiffer RF. Autonomic Dysfunction in Parkinson's Disease. Neurotherapeutics : the 
journal of the American Society for Experimental NeuroTherapeutics 2020;17:1464-
1479. 
3. Kaufmann H, Norcliffe-Kaufmann L, Palma JA. Baroreflex Dysfunction. The New 
England journal of medicine 2020;382:163-178. 
4. Velseboer DC, de Haan RJ, Wieling W, Goldstein DS, de Bie RM. Prevalence of 
orthostatic hypotension in Parkinson's disease: a systematic review and meta-analysis. 
Parkinsonism Relat Disord 2011;17:724-729. 


 
Protocol Summary (ERICA) 
 
IRB_00152581 
Page 4 of 9 
 
IRB Approval 4/10/2023 
 
5. Hiorth YH, Pedersen KF, Dalen I, Tysnes OB, Alves G. Orthostatic hypotension in 
Parkinson disease: A 7-year prospective population-based study. Neurology 
2019;93:e1526-e1534. 
6. De Pablo-Fernandez E, Tur C, Revesz T, Lees AJ, Holton JL, Warner TT. Association 
of Autonomic Dysfunction With Disease Progression and Survival in Parkinson 
Disease. JAMA neurology 2017;74:970-976. 
7. Bouhaddi M, Vuillier F, Fortrat JO et al. Impaired cardiovascular autonomic control in 
newly and long-term-treated patients with Parkinson's disease: involvement of L-dopa 
therapy. Auton Neurosci 2004;116:30-8. 
8. Senard JM, Rai S, Lapeyre-Mestre M et al. Prevalence of orthostatic hypotension in 
Parkinson's disease. J Neurol Neurosurg Psychiatry 1997;63:584-589. 
9. Goldstein DS, Eldadah BA, Holmes C et al. Neurocirculatory abnormalities in 
Parkinson disease with orthostatic hypotension: independence from levodopa 
treatment. Hypertension 2005;46:1333-9. 
10. Jost WH, Altmann C, Fiesel T, Becht B, Ringwald S, Hoppe T. Influence of levodopa 
on orthostatic hypotension in Parkinson's Disease. Neurol Neurochir Pol 2020;54:200-
203. 
11. Perez-Lloret S, Rey MV, Fabre N et al. Factors related to orthostatic hypotension in 
Parkinson's disease. Parkinsonism & related disorders 2012;18:501-5. 
 
 
 
Purpose and Objectives 
 
We propose to investigate the effects of levodopa on cardiovascular autonomic function in 
patients with Parkinson’s Disease with orthostatic hypotension (PD+OH) and Parkinson’s 
Disease without neurogenic orthostatic hypotension (PD-OH) by performing standardized 
autonomic testing in the same patients on and off levodopa. 
Objectives 
AIM #1. The primary objective of the study is to investigate the effect of levodopa on 
cardiovascular autonomic function in participants with PD (with and without OH) 
Participants with PD+OH and PD-OH will undergo autonomic testing of baroreflex 
cardiovagal and sympathetic noradrenergic functions on and off of levodopa on two separate 
days. The primary endpoint will be the change in systolic blood pressure from supine to tilt at 
3 minutes. Results of autonomic testing on levodopa will be compared to testing off levodopa 
in all participants. Each patient will be his or her own control. Secondary endpoints will 
include validated indices of baroreflex cardiovagal and baroreflex sympathetic noradrenergic 
functions. Although levodopa may have a mild hypotensive effect, we hypothesize that 
levodopa will not induce or worsen the drop in blood pressure from supine to tilt at 3 minutes 
and will not worsen neurogenic orthostatic hypotension. Planned secondary endpoints will also 
investigate the differences in orthostatic vital signs with active standing and tilt table testing in 
patients with PD and the relationship between autonomic testing and the orthostatic symptom 
severity questionnaire. 


 
Protocol Summary (ERICA) 
 
IRB_00152581 
Page 5 of 9 
 
IRB Approval 4/10/2023 
 
  
AIM #2. Determine if levodopa has a different effect on cardiovascular autonomic function in 
participants with PD+OH compared to participants with PD-OH 
The data from autonomic testing performed for AIM#1 will be used to assess AIM#2. The 
primary endpoint for AIM#2 will be indices of baroreflex cardiovagal and noradrenergic 
function. We hypothesize that levodopa will not alter baroreflex cardiovagal and sympathetic 
noradrenergic functions in either PD+OH or PD-OH.  
 
 
 
Study Population 
 
Age of Participants: 18+ 
 
Sample Size: 
At Utah: 
  
All Centers: 
40 
 
Inclusion Criteria: 
All participants: 
- Age 18 or older 
- Diagnosis of PD based on consensus criteria (Movement Disorder Society Criteria for 
Parkinson’s disease) [13]. 
For PD+OH group: 
 
- Orthostatic hypotension defined by sustained drop in systolic blood pressure > 20 mmHg 
and/or a drop in diastolic blood pressure > 10 mmHg within 3 minutes from supine to 
standing during active standing or tilt [14]. 
- Autonomic testing and a ratio orthostatic heart rate change / systolic blood pressure change 
< 0.5 bpm/mmHg will confirm a neurogenic etiology [15]. 
References 
13. Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, et al. MDS clinical 
diagnostic criteria for Parkinson's disease. Movement disorders : official journal of the 
Movement Disorder Society. 2015;30(12):1591-601. 
14. Freeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E, Biaggioni I, et al. 
Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope 
and the postural tachycardia syndrome. Clin Auton Res. 2011;21(2):69-72. 
15. Norcliffe-Kaufmann L, Kaufmann H, Palma JA, Shibao CA, Biaggioni I, Peltier AC, et 
al. Orthostatic heart rate changes in patients with autonomic failure caused by 
neurodegenerative synucleinopathies. Ann Neurol. 2018;83(3):522-31. 


 
Protocol Summary (ERICA) 
 
IRB_00152581 
Page 6 of 9 
 
IRB Approval 4/10/2023 
 
 
 
Exclusion Criteria: 
Participant exclusion criteria 
- Current usage of medications with potential to affect autonomic or sensory testing, in 
which the medication can’t be held 48 hours prior to testing (e.g. antihypertensives, muscle 
relaxants, stimulants, and some antidepressants that alter sympathetic function). Participants 
will be instructed to obtain approval from prescribing providers in cases a medication must 
be held 
- Cognitive impairment according to the principal investigator that would limit the ability to 
follow instructions during testing 
- Usage of dopamine agonists -- this class of medication is associated with orthostatic 
hypotension and residual medication effects may confound the results of the study due to the 
long half-life 
- Contraindication to the Valsalva maneuver (known middle ear damage or disease, Moya-
Moya disease, myocardial infarction within 6 months, and retinal detachment within 6 
months) 
 
 
Design  
 
Prospective Biomedical Intervention or Experiment 
 
 
 
Study Procedures 
 
Recruitment/Participant Identification Process: 
- Potential participants with PD will be identified from the movement disorders clinic. The 
principal investigator (Dr. Guillaume Lamotte) will be responsible to review charts and 
medical records to ensure eligibility. Co-investigators listed on the IRB as well as other U of 
Utah Healthcare providers who have been made aware of the study, may offer enrollment to 
potential participants in person in a clinic setting. In the event that a patient expresses interest 
in participating in research, our principal investigator (or approved study personnel) will 
contact the patient to provide additional information regarding the study. 
- Information about the study will also be displayed in the movement disorder bi-annual 
newsletter. Research study flyers will be available for all patients seen in the movement 
disorders clinic. The flyers will be available in the waiting room. Participants can also be 
recruited from the community through local PD Support Groups and word of mouth, and can 
contact the primary investigator (or approved study personnel) to inquire about screening for 
the study. Advertisement on the University of Utah study locator website may also be used as 
a recruitment method. 
 
 
Informed Consent: 


 
Protocol Summary (ERICA) 
 
IRB_00152581 
Page 7 of 9 
 
IRB Approval 4/10/2023 
 
Description of location(s) where consent will be obtained:  
Consent will be obtained in a dedicated space for clinical assessments of research subjects at 
University of Utah Headache Clinic (INC), University of Utah Neurology/Neurosurgery Clinic 
(INC and CNC), or Headache Physiology Laboratory (383 Colorow Drive).  
 
Description of the consent process(es), including the timing of consent:  
The principal investigator (or approved personnel) will obtain consent prior to performing any 
of the study procedures, and will explain the necessary information to allow the subject to 
make an informed decision about participation in the study. During the consent process, the 
background and purpose of the study, the study procedures, review the risks and benefits of 
the study, and review the process involved in the protection of personal identifiable 
information will be explained. Inclusion and exclusion criteria for the study will also be 
reviewed. Participants will have time to discuss any questions or concerns with the principal 
investigator. Throughout the study, study personnel will also give participants opportunities to 
ask questions and get more information about the study protocol for ongoing informed 
consent. 
 
Procedures: 
Screening: When the PI (or approved study personnel) makes contact with potential 
participant, basic information will be obtained to determine eligibility, including: medical 
history, PD diagnosis date and symptoms, current medications, among others. 
Consent Process: Informed consent will be completed. Participants will complete the 
informed consent form on paper, or via REDCap. Participants will receive a paper copy per 
their request. Prior to signing the consent form, study personnel will thoroughly explain all 
study procedures and provide participants with ample time to ask any questions. The study 
team will continue to provide participants with opportunities to ask questions to ensure 
ongoing informed consent throughout the progress of the study. 
Clinical assessment: The primary investigator will perform a medical history and physical 
examination before the testing procedures (baseline visit). The baseline visit will be performed 
on levodopa. The scales and assessments will include the Composite Autonomic Symptoms 
Score 31 (COMPASS 31), the Movement Disorder Society-Sponsored Revision of the Unified 
Parkinson's Disease Rating Scale (MDS-UPDRS) part I, II, III, and Hoehn and Yahr stage. 
The clinical assessment and scales are part of the standard of care in PD. Orthostatic vital 
signs (standing and supine measures of heart rate and blood pressure) will be performed 
during the baseline visit with active standing and the day of off-levodopa autonomic testing. 
 
Autonomic testing: All participants will undergo autonomic testing on two separate days. The 
first autonomic testing will occur within 4 weeks of the baseline visit. The two autonomic tests 
will occur within a 2-week timeframe. To avoid any confounding of treatment effects and 
period effects, the order of testing (on versus off levodopa) will be randomized so testing on 
the first day will be on-levodopa for half of the participants and off-levodopa for the other 
participants. The procedures performed in this study are part of standardized clinical 
autonomic function testing. Autonomic testing will be performed by a research assistant with 
expertise in autonomic testing. 


 
Protocol Summary (ERICA) 
 
IRB_00152581 
Page 8 of 9 
 
IRB Approval 4/10/2023 
 
Each participant will undergo testing in the on-levodopa state (45min to 1h after taking their 
regular dose of levodopa in the morning) and off-levodopa state. For testing in the off-state, 
the last dose of levodopa will be taken at least 12 hours before testing. Off-state in PD is 
expected to cause some degree of discomfort related to re-emergence / exacerbation of the 
motor and non-motor symptoms of PD. To limit the duration of the off-state, autonomic 
testing will be performed early in the morning between 7am and 8am. As soon as the 
autonomic testing is completed, the participant will be allowed to take levodopa. A participant 
may not be eligible for the study if the investigator believes that holding levodopa for testing 
is not safe. Briefly withholding levodopa, and/or medications that can interfere with heart rate 
or blood pressure measures, on the morning of the test is part of standard clinical autonomic 
function testing and is known to be well tolerated based on extensive clinical experience of the 
PI. 
Participants will be instructed to have a standardized low-carbohydrate meal in the morning to 
avoid the confounding effects of postprandial hypotension and instructed to maintain a stable 
fluid intake to avoid volume shifts. 
Autonomic testing will include non-invasive monitoring of blood pressure and heart rate 
during the Valsalva maneuver and during a 10-minutes head-up tilt. 
Electrocardiogram (ECG): For monitoring the ECG, electrocardiographic leads are applied to 
the chest, abdomen, neck, or arms. All participants have ECG monitoring during the Valsalva 
maneuver and tilt table testing described below. Measurement of beat-to-beat heart rate part of 
standard clinical autonomic function testing. 
 
Finger blood pressure measurement: A finger cuff is applied for non-invasive measurement of 
continuous blood pressure. All participants have finger blood pressure monitoring during the 
Valsalva maneuver and tilt table testing described below. Tracking blood pressure 
continuously via a finger cuff device is part of standard clinical autonomic function testing. 
 
Brachial blood pressure: A clinical automated brachial cuff is applied for measurement of 
brachial blood pressure. All participants have brachial blood pressure monitoring before and 
during head-up tilt table testing. Measuring brachial blood pressure is part of standard clinical 
autonomic function testing. 
 
Respiration: A device for continuous monitoring of respiration is applied to the chest. All 
participants have respiratory monitoring during the experimental manipulations described 
below, unless technical limitations obviate such monitoring. Monitoring respiration is part of 
standard clinical autonomic function testing. 
Valsalva maneuver: Assessment of beat-to-beat blood pressure and heart rate during and after 
performance of the Valsalva maneuver is a well-accepted standard autonomic function test. 
The participant lies supine on a tilt table with head on pillow. The participant blows or strains 
against a resistance for 12 seconds at 40 mmHg and then relaxes. If a “square wave” 
phenomenon is observed, the subject may be tilted at 20 degrees head up and the procedure 
repeated. At least 3 Valsalva maneuvers are done. The maneuvers are repeated (at least 1 
minute between repetitions), until a technically adequate recording is obtained. Indices of 


 
Protocol Summary (ERICA) 
 
IRB_00152581 
Page 9 of 9 
 
IRB Approval 4/10/2023 
 
baroreflex-cardiovagal and cardiovascular noradrenergic functions are derived from the heart 
rate and blood pressure responses to the Valsalva maneuver. Indices of baroreflex cardiovagal 
function include the Valsalva ratio derived from the maximum heart rate generated by the 
Valsalva maneuver divided by the lowest heart rate occurring within 30 s of the peak heart rate 
and the slope of the relationship between cardiac R-R interval vs. systolic blood pressure in 
Phase II of the Valsalva maneuver is taken as a measure of baroreflex-cardiovagal gain (BRS-
V). Indices of baroreflex cardiovascular noradrenergic function include the difference in BP 
between baseline and the end of Phase II, the pressure recovery time (PRT) which is the time 
from the nadir of the systolic blood pressure in Phase III of the Valsalva maneuver to complete 
return of systolic blood pressure to baseline, the adrenergic baroreflex sensitivity which is 
calculated from the slope of the line reflecting the difference of the baseline systolic blood 
pressure and the lowest systolic blood pressure in Phase III and the areas below the baseline 
systolic blood pressure calculated in Phase II (BRA-II) and IV (BRA-IV) of the Valsalva 
maneuver. 
 
Head-up tilt table testing: The participant lies supine for at least 10 minutes after placement of 
monitoring leads. Baseline hemodynamic measures are taken. Then the participant is tilted 
head-up to 70 degrees from horizontal using a motorized tilt table. The duration is up to 10 
minutes but may be less for safety reasons if the blood pressure decreases rapidly and 
progressively. Hemodynamic measures are taken at regular interval during and after tilt. Head-
up tilt is part of standard clinical autonomic function testing. 
 
Statistical Methods, Data Analysis and Interpretation 
 
Summary statistics will be used to describe demographic and clinical variables. A sample size 
of 40 will achieve a power of 80% and a level of significance of 5%, for detecting a mean of 8 
mmHg in ΔSBP-3’ between the ON and OFF states with a within subject standard deviation of 
20 mmHg based on published data on the effect of levodopa on supine and standing blood 
pressure in people with PD. The main statistical analysis will be conducted using mixed-
effects regression models (linear mixed models), which will allow for the correlation of 
repeated measures within subjects. The response variable in our models will be ΔSBP-3’, and 
the primary predictors will be the ON vs. OFF levodopa state and the period (visit 2 versus 
visit 3). A random intercept will be included for each subject to account for the within-subject 
correlation. For analyses of secondary outcomes, we will fit a mixed effect model and adjust 
the p value for multiple comparisons using the Hochberg multiple comparison procedure. 
Changes in blood pressure and heart rate with active standing and indices of baroreflex 
cardiovagal and sympathetic noradrenergic function OFF levodopa will be compared between 
PD+OH and PD−OH with Student t tests.