A Pilot Study of the Effect of Dietary Sodium Intake on Assessments of Vascular Endothelium
Phase: NA
Conditions: Postural Tachycardia Syndrome (POTS)
Sponsor: Vanderbilt University Medical Center

 
 
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A Pilot Study of the Effect of Dietary Sodium Intake on Assessments of Vascular 
Endothelium 
A Sub-study of “Dietary Salt in Postural Tachycardia Syndrome” 
 
PI: Emily M. Garland, PhD 
Department of Pharmacology 
Vanderbilt University School of Medicine 
AA3228 MCN 
Nashville, TN 37232-2195 
 
 Victor Nwazue MB ChB,  Satish R. Raj, MD, MSCI, Jorge Celedonio Colquicocha, MD, David 
Robertson, MD, Italo Biaggioni MD, Cyndya A. Shibao MD, Alfredo Gamboa MD, Luis Okamoto 
MD, Amy Arnold PhD, Mary Ginnie Farley, Sachin Y. Paranjape BS, Bonnie K. Black, RN NP 
Division of Clinical Pharmacology 
Vanderbilt University School of Medicine 
Nashville, TN 37232 
 
 
 
CllinicalTrials.gov ID#: NCT01550315 
 

 
 
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1.0 BACKGROUND 
1.1 Endothelium 
The endothelium is the thin layer of cells that lines the interior surface of blood vessels.  
It functions as an inert barrier between the vascular system and all other body tissues.  
Additionally, it aids in modulating hemostasis, growth, tone and inflammation throughout the 
circulatory system.  The endothelium maintains the vasculature in a steady dilated state.  
Endothelial dysfunction has been identified in several pathologic states such as diabetes, 
hypertension, age, cigarette smoking, obesity and several cardiovascular diseases 1, 2.  The 
pathophysiology of endothelial dysfunction is not fully understood.  Studies have demonstrated 
impairment in nitric oxide (NO) metabolism of which several mechanisms have been postulated 
including: abnormally elevated asymmetric dimethylarginine (ADMA) level- a potent 
endogenous competitive inhibitor of NO 3, overproduction of free radicals which have been 
identified in patients with elevated cholesterol and coronary artery disease and reduction in NO 
synthesis 4-6.  Impaired availability of NO has been implicated in the development of coronary 
artery disease, and poorly controlled hypertension 7.  
 
1.2 Dietary Sodium Levels 
According to the most recent report by institute of medicine (IOM), most Americans 
consume an average of sodium in excess of 3400 mg.  This far exceeds the center for disease 
(CDC) recommendation8 of less than 2300 mg or less than 1500 mg for high risk groups with 
hypertension, diabetes, African Americans, or chronic kidney disease.  The American Heart 
Association has recently recommended an average dietary sodium intake not exceeding 1500 mg 
across all age groups 9. 
Dietary sodium have been implicated  in endothelial dysfunction, with increasing 
evidence linking salt intake to increased risk of cardiovascular disease and elevated blood 
pressure 10.  Excess salt intake in mammalian study has demonstrated increased mortality by 
accelerating arteriosclerosis and renal parenchyma damage 11.  Strazullo at al. performed a meta- 
analysis that suggested a significant increased risk of stroke and total cardiovascular events 
among those with a high salt diet 12.   
 
1.3. Endothelial dysfunction and oral salt diet 
Short-term high salt intake has been shown to produce reductions in NO as reported by 
Dishy et al. 13.   Elevated ADMA was also implicated in patients with high salt diet by a study 
reported by Fujiwara et al. 14.  Many of these studies have assessed patients on their native diets, 
and thus may be confounded my many unknown variables.  Most of these studies were also 
carried out on middle aged or older patients with cofounding risk factors such as hypertension.  
We propose to study young to middle aged subjects who will undergo acute, but steady state 
HIGH and LOW sodium diets, and assess the acute changes in measures of endothelial events.  
Differences in measures of endothelial function between the diet phases might suggest that 
dietary sodium intake is an important variable that would need to be controlled in future studies 
of endothelial function. 
2.0 REACTIVE HYPEREMIA PULSITLE ARTERIAL TONOMETRY (RH-PAT) 
2.1 RH-PAT Device 

 
 
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The principle of PAT, a finger plethysmographic device that allows the isolated detection 
of pulsatile arterial volume changes, has been described 15, 16. This device (Itamar Medical Ltd., 
Caesarea, Israel) consists of two finger-mounted probes, which include a system of inflatable 
latex air-cushions within a rigid external case. The probe design allows the application of a 
constant and evenly distributed near-diastolic counter-pressure within the entire probe, which 
increases sensitivity by unloading arterial wall tension, and prevents venous blood pooling to 
avoid venoarteriolar reflex vasoconstriction. Pulsatile volume changes of the fingertip are sensed 
by a pressure transducer and transferred to a personal computer where the signal is band pass-
filtered (0.3 to 30 Hz), amplified, displayed, and stored. 
 
2.2 RH-PAT and Other Methods for Assessing Vascular Endothelial Function in Vivo 
Reactive hyperemia, which is due to dilation of small resistance vessels, is partly 
mediated by endothelium-derived NO and, therefore, the magnitude of the hyperemic response 
serves 
as 
an 
indicator for the 
status 
of 
endothelial 
function 
17, 
18. 
Moreover, using 
strain-gauge 
plethysmography, 
an 
excellent 
correlation 
between 
peak 
forearm 
blood 
flow 
response 
during RH and 
that 
to 
intra-
arterial 
infusion 
of 
the 
endothelium-
dependent 
vasodilator 
acetylcholine has been demonstrated, indicating that the magnitude of RH may serve as an index 
of peripheral endothelial function 19; RH-PAT permits the noninvasive assessment of peripheral 
vascular reactivity by measuring digital pulse volume at rest and during RH. Notably, although 
local, systemic, and environmental factors may modulate digital pulse volume, this parameter 
also depends on the bioavailability of NO 20. Moreover, endothelium-derived NO has been 
shown to be particularly important for the regulation of vascular tone in areas rich in 
arteriovenous anastomoses, such as the finger tip 21. The effect of NO synthesis inhibition by Nω-
nitro- -arginine methyl ester (  -NAME) on the PAT response to reactive hyperemia was 
investigated recently22. In that study, 19 healthy volunteers underwent RH-PAT testing, 
according to the same protocol as was used in the present study, before and after administration 
of 
-NAME into the brachial artery. Importantly, 
-NAME administration was associated with 
a significant 61% reduction (p < 0.05) in the RH-PAT index values, indicating that this index 
depends on endothelium-derived NO and, therefore, represents a marker of peripheral 
 
Figure 5: RH-PAT responses before and after brachial artery occlusion. 

 
 
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endothelial function. In accordance with these findings, it was demonstrated that factors known 
to affect endothelial function, including various cardiovascular risk factors and the presence of 
CAD, influence RH-PAT index values in a similar manner as flow-mediated dilation (FMD) of 
the brachial artery, a widely-used method to evaluate peripheral endothelial function 15. 
Furthermore, a significant relationship between the PAT response to reactive hyperemia and 
flow-mediated dilation of the brachial artery has been shown, suggesting that vascular reactivity 
of the digital vasculature, as measured by the RH-PAT index, is influenced by endothelial 
function in a magnitude and direction similar to that of the brachial artery 15. 
 
Vasodilatation of a peripheral conduit artery following an increase in luminal blood flow 
and internal-wall shear is known as flow-mediated dilatation (FMD). In practice it is performed 
following a period of distant limb ischemia. Strong evidence suggests that FMD is a valid 
endothelium-dependent and NO-specific index of endothelial function. To measure FMD we will 
adhere to current guidelines 23, 24. 
 
3.0 EX-VIVO ASSESSMENT OF ENDOTHELIAL FUNCTION 
 
The endothelium can no longer be viewed as the passive inner cover of the vessel wall. It 
plays a central role in cardiovascular regulation. Endothelial cells produce a variety of vasoactive 
substances that can act locally or at distant sites. Among these substances nitric oxide (NO) is 
probably the most heavily studied, and its reduced bioavailability is widely accepted to be 
responsible for endothelial dysfunction. Reduction of NO bioavailability can result from a 
defective eNOS expression/activity or from an excessive NO degradation, usually through an 
interaction with superoxide (O-2) that generates peroxynitrites (ONOO-). Endothelial damage is 
the first step of vascular remodeling. Unfortunately, the endothelium has a limited ability to 
repair itself and hence prevent or reverse endothelial dysfunction. In animal models, direct 
information on the anatomical and function integrity of the endothelium can be easily obtained. 
In humans, endothelial function is usually assessed indirectly as the NO-dependent vasodilatory 
capacity of a given vascular bed to an endothelial stimulus either mechanical (shear stress, 
reactive hyperemia) or pharmacological (NO-dependent vasodilators, NOS inhibitors). This 
indirect approach is however subjected to intra-patient variability, confounding effects, and 
cannot distinguish between anatomical and functional alterations. Other clinical indicators of 
endothelial dysfunction are represented by circulating substances such as VCAM-1, ICAM, 
vWF, ADMA, and thrombomodulin, indicating pathological activation of the endothelium in the 
setting of a low grade inflammatory state. Relatively recently, more direct ex vivo approaches 
have been developed to study the human endothelium, these include the study of mature 
circulating endothelial cells that may detach at an increase rate due to ongoing endothelial 
damage and can be isolated and incubated. Similarly, circulating endothelial progenitor cells, 
discovered in 1997, can be obtained and cultivated to study mechanisms of vascular repair and 
regeneration. A third method involves the harvesting of viable endothelial cells via an 
endothelial biopsy, this allow the study of gene and/or protein expression. 
 
 
Endothelial biopsy has been used to quantify eNOS expression (by measuring the protein 
expression of eNOS), its activity [by measuring Ser-1177 phosphorylated eNOS (P-eNOS)] and 
also NO-dependent reactive oxygen induced stress (by measuring nitrotyrosine). Ideally samples 
from a suspected damaged artery (coronary) should be obtained, either during routine cardiac 
catheterization or after the procedure has been performed, however this is not always possible to 

 
 
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do. Vein sampling has the advantage of its accessibility and it has reported a good correlation 
(r=0.7) for protein expression of eNOS, P-eNOS and nitrotyrosine from samples obtained form a 
peripheral artery and the brachial artery.  
 
 
4.0 HYPOTHESIS & SPECIFIC AIMS 
4.1 Hypothesis 
In this pilot crossover study, we will test the hypothesis that markers of vascular 
endothelial dysfunction will be exaggerated acutely with an extreme high-sodium diet compared 
to an extreme low-sodium diet. 
 
4.2 Specific Aims 
1. To assess whether RH-PAT (marker of peripheral small vessel endothelium dependent 
nitric oxide mediated vasodilatation) will be reduced in subjects on a high sodium diet 
compared with a very low sodium diet.  
2. To assess whether brachial artery flow-mediated vasodilatation (marker of endothelium 
dependent nitric oxide mediated vasodilatation in a conductance vessel) is reduced on 
extreme high sodium diet compared to a low sodium diet. 
3. To assess whether circulating markers of endothelial function will be reduced in subjects 
on a high sodium diet compared with a very low sodium diet. 
4. To assess whether calf blood flow in response to reactive hyperemia (CBF-RH) correlates 
with RH-PAT. 
 
5.0 INCLUSION/EXCLUSION CRITERIA 
5.1 Inclusion Criteria 
• Subjects will be enrolled in the parent study “Dietary Salt in Postural Tachcyardia 
Syndrome” funded by R01 HL102387  
• Postural Tachycardia Syndrome 
o Diagnosed with postural tachycardia syndrome by the Vanderbilt Autonomic 
Dysfunction Center 
 Increase in heart rate ≥30 beats/min with position change from supine to 
standing (10 minutes) 
 Chronic symptoms consistent with POTS that are worse when upright and 
get better with recumbence 
• Control Subjects 
o Healthy, non-obese, non-smokers without orthostatic tachycardia 
o Selected to match profiles of POTS patients (gender, age) 
o Not using vasoactive medication 
• Age between 18-60 years 
• Male and female subjects are eligible. 
• Able and willing to provide informed consent 
 
5.2 Exclusion Criteria 
• Overt cause for postural tachycardia (such as acute dehydration) 
• Inability to give, or withdrawal of, informed consent  
• pregnant 

 
 
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• Other factors which in the investigator’s opinion would prevent the subject from 
completing the protocol. 
 
6.0 ENROLLMENT, RANDOMIZATION & BLINDING  
6.1 Recruitment  
For the parent study, the patients with orthostatic intolerance will be recruited from 
patients referred to the Vanderbilt University Autonomic Dysfunction Center. Control subjects 
will be recruited from the Autonomic Research Database, the VICTR Research Participant 
Database, and advertising within the Vanderbilt Community.  For this protocol, subjects enrolled 
in the parent study will be approached about this sub-study. Subjects will be assured that they are 
not required to participate in this study even if they choose to participate in the parent study. 
 
6.2 Randomization 
There will be no randomization for this specific sub-study. The order of diets (low 
sodium vs. high sodium) will be performed as a part of the parent study, and not as a part of this 
sub-study.   
 
6.3 Blinding 
None. 
 
7.0 STUDY PROCEDURE 
7.1 Screening 
All subjects will be previously screened and evaluated as a part of the parent study.  No 
further screening will be performed exclusively for this study. Women of childbearing potential 
will have had a serum pregnancy test as a part of the parent study. Pregnant women will not be 
allowed to participate. 
 
The history will include (but not be limited to): 
• Framingham Risk factors (age, gender, smoking, hypertension, dyslipidemia) 
• Metabolic diseases (metabolic syndrome, polycystic ovary syndrome, diabetes) 
• Inflammatory diseases (e.g. rheumatoid arthritis).  
The physical examination will include (at minimum): 
• Height 
• Weight 
• Waist circumference 
• Hip circumference 
• Orthostatic vital signs.  
 
 
 
7.2 Study Design 
The study will involve a crossover design in which each subject will be assessed (as 
below) while on a very low-sodium (10 mEq/day) diet compared with a very high-sodium diet.  
These acute dietary interventions will be part of the parent study (“Dietary Salt in Postural 
Tachcyardia Syndrome” funded by R01 HL102387) for 4-5 days at the time of the study.  

 
 
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Dietary success will be assessed using a 24h urine for sodium and creatinine as a part of the 
parent study. 
 
7.2.1 Blood work 
 
Blood will be drawn and collected in a fasting state for future assay and analysis of the 
following tests: 
• Glucose, Insulin (glucose impairment, insulin resistance) 
• Fasting lipid profile 
• C-Reactive Protein (hsCRP) (inflammatory state) 
• Inflammatory cytokines (inflammatory state) 
• F2-isoprostanes (oxidative stress) 
• PAI-1 antigen, fibrinogen (prothrombotic state) 
 
7.2.2. Urine Collection 
 
A morning urine sample will be collected, and an aliquot saved for urinary isoprostanes. 
 
7.2.3 Pulsitile Arterial Tonometry (PAT) Protocol 
• Performed on Day 6 of parent protocol (5 days of low/high sodium diet). 
• All studies will be performed in a fasting state or at least 2 hours following a meal.  
• Subjects will be studied in the supine position and both hands on the same level in a 
comfortable, thermoneutral environment. 
• A blood pressure cuff will be placed on one upper arm (study arm; non-dominant), while the 
contralateral arm will serve as a control (control arm). 
• RH-PAT probes will be placed on one finger (finger II, III, or IV) of each hand (same finger 
on both hands). The fingers on either side of the one with the probe will be separated using 
soft sponge rings. 
• Continuous recording of pulsatile blood volume responses from both hands will be initiated. 
• After a 10-min equilibration period, the blood pressure cuff on the study arm will be inflated 
to 60 mm Hg above systolic pressure for 5 min. The cuff will then be deflated to induce 
reactive hyperemia, PAT recording will be stopped. 
 
7.2.4 PAT Analysis 
 
The RH-PAT data will be analyzed by a computer in an operator-independent manner. As 
a measure of the extent of reactive hyperemia, the RH-PAT index was calculated as the ratio of 
the average amplitude of the PAT signal over a 1-min time interval starting 1 min after cuff 
deflation divided by the average amplitude of the PAT signal of a 3.5-min time period before 
cuff inflation (baseline). RH-PAT index values from the study arm were then normalized to the 
control arm to compensate for potential systemic changes.  
 
7.2.5 Calf Blood Flow in Reactive Hyperemia (CBF-RH) 
 
Calf blood flow (CBF) will be determined using venous occlusion plethysmography and 
calibrated mercury strain-gauges (EC-6, D.E. Hokanson Inc., Bellevue, Washington, USA) 
during reactive hyperemia after a 5 min of ischemia of the distal limb. Strain-gauges will be 
applied to the widest part of the non-dominant calf (~10 cm below patella). Participants will 
remain quietly supine for 10 min with legs elevated on foam pads above the right atrium to 
achieve stable baseline measurements of CBF. The venous occlusion cuff is inflated for 4 seconds at 

 
 
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8 seconds intervals, while monitoring the change in resistance in the system, pressure inside the 
measuring cuff, and 5-10 determinations are performed The plethysmograph output signal will be 
transmitted recorded using the WINDAQ data acquisition system (DI220, DATAQ, Acron, OH, 14 Bit, 
500Hz) and processed off-line. The slope will be express as milliliters (ml) per minute per 100 ml 
of forearm tissue (ml/min/100 ml tissue). After 1 minute of ankle cuff inflation to 50 mm Hg 
above subject’s systolic blood pressure to occlude ankle circulation, resting blood flow will be 
measured as the average of the last 4 of 5 plethysmographic measurements for 1 minute. Peak 
CBF will be then measured after 5 minutes of ischemia using a cuff inflated to 50 mm Hg above 
subject’s systolic blood pressure, using a cuff located proximal to the patella. Again one minute 
before thigh cuff release, the ankle cuff will be inflated to 50 mm Hg above subject’s systolic 
blood pressure, and measurements of CBF will be repeated for the next 3 minutes. 
 
7.2.6 Protein expression of harvested endothelial cells 
 
A 20-gauge intravenous catheter will be inserted into a superficial forearm vein. Under 
sterile conditions, 3 J-shaped vascular guidewires will be sequentially advanced into the vein up 
to 10 cm. Endothelial cells will be retrieved from the wire tips by washing with cell dissociation 
buffer (Invitrogen) at 4 C. Endothelial cells will be recovered by centrifugation and fixed with 
3.7% formaldehyde in PBS for 10 minutes, washed twice with PBS, transferred to poly-L-lysine 
coated slides (Sigma), and air dried at 37C. The slides will be then stored at -70 C until 
analyzed. 
 
Using this procedure it is possible to measure basal eNO production and activity 
measuring venous endothelial expression of total eNOS and activated eNOS (P-eNOS) by 
quantitative immunofluorescence. Vascular inflammation and oxidative stress can be determined 
by measuring venous endothelial expression of nuclear factor-B (NFB) and nitrotyrosine. 
 
7.2.6 Evaluation of Forearm-Mediated Dilation 
Subjects will be fasting for at least 2 hours prior to the study and will be instructed to 
avoid exercising the day before the study. All studies will be conducted in a quiet, temperature-
controlled room. All subjects will rest in the supine position for at least 30 minutes after all 
instrumentation procedures are done. The arm will be kept extended and immobilized at heart 
level. Brachial artery diameter will be measured using a high resolution ultrasonography (iU22 
xMatrix Ultrasound System, Philips, Andover MA) using a linear array probe with a 5 to 17 
MHz frequency range (L17-5 Broadband Linear Array Transducer, Philips, Andover MA). The 
brachial artery will be imaged in longitudinal sections, 5-10 cm proximal to placement of an 
occlusion cuff in the dominant forearm just below the antecubital fossa. The probe will be held 
with a stereotaxic holder with micrometer movement capabilities.  
When the clearest B-mode image through the center of the vessel is obtained with 
optimal contrast between the anterior and posterior vessel walls and the lumen of the vessel, the 
stereotaxic clamp will be fixed in place. Baseline diameter will be examined before cuff inflation 
for at least 1 minute. The rapid occlusion cuff (Hokanson) will be inflated and maintained for 5 
minutes at 50 mm Hg above the subject’s systolic blood pressure to produce transient ischemia. 
Measurement of post-deflation diameter will be initiated before cuff release and continue for 5 
minutes following deflation.  
Flow velocity and brachial artery diameter will be continuously measured using duplex 
ultrasound. Blood velocity will be assessed using an insonation angle <60. The B-mode will 

 
 
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update synchronously with the R-wave of the ECG while also having a continuous Doppler 
spectrum recording throughout.  
One experienced sonographer will collect all images. Images will be digitized from the 
video output of the ultrasound machine using a frame grabber on a personal computer. Image 
acquisition will be gated with an ECG signal so that images will be captured at end diastole at 
each cardiac cycle.  
Brachial artery diameter will be assessed by a single trained operator using an automated, 
beat-by-beat edge detection and wall-tracking image processing software (Vascular Tools 5.0, 
Medical Imaging Applications, USA). Peak diameter will be calculated using automated 
mathematical algorithms. Data will be presented as absolute (mm) and relative FMD response 
(%). The area under the curve until peak diameter will also be measured and presented. 
 
7.3 
Study Outcome Measures 
• RH-PAT index 
• Brachial artery diameter changes. 
• CBF-RH 
• Other blood parameters (outlined in section 7.2.1) 
 
8.0 STATISTICAL CONSIDERATIONS 
8.1 Primary Analysis 
The primary outcome measure will be the RH-PAT index. The primary analysis will 
involve a non-parametric, paired, Signed Rank test of RH-PAT between all subjects (POTS 
patients and control subjects) on the high sodium diet vs. the low sodium diet.  
 
8.2 Secondary Analysis 
Secondary analyses will include non-parametric paired comparisons between low sodium 
and high sodium diets of continuous outcome measures (outlined in section 7.3). Secondary 
comparisons might also assess differences in the dietary sodium induced changes between POTS 
patients and control subjects. 
 
8.3 Sample Size Calculation 
As this is a pilot study, there are no preliminary data available on the RH-PAT index in 
different sodium diets. Published data indicate that the RH-PAT index in 39 healthy subjects 
without endothelial function is 1.78±0.08 (mean±SEM) 25. In the same study, RH-PAT<1.35 was 
found to be the best discriminator of coronary endothelial function. We will designate a more 
conservative ΔRH-PAT=0.25 as a clinically significant difference between high sodium diet vs. 
low sodium diet for the entire group. We expect the standard deviation around the difference will 
be 0.5 (based on the above data), for an effect size of 0.5. With the aforementioned assumptions 
for a paired test of continuous data, and a 0.05 two-sided significance level, a sample size of 44 
(combined POTS patients and control subjects) would give 90% power to detect this difference 
26. To account for drop-outs, we propose to enroll up to 50 subjects in total from the parent study.  
Using the same assumptions, 33 subjects would give 80% power to detect the same difference (in 
case of enrollment difficulties for this sub-study). 
 
9.0 RISKS & INCONVENIENCES 

 
 
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1. Having blood drawn may hurt, may cause bruising and may cause lightheadedness or rarely 
fainting. 
2. The finger probes may be tight and uncomfortable. 
3. The blood pressure cuffs may be uncomfortable. 
 
10.0 DATA & SAFETY PLAN 
10.1 Adverse Event (or Unanticipated Problem) Reporting 
 
Any adverse events of a serious nature will be reviewed immediately with the principal 
investigator. Serious adverse events will be reported in writing to the Vanderbilt IRB per IRB 
regulations. All non-serious adverse events will be summarized once a year, during the annual 
review to the IRB. C. Victor Nwazue MB ChB will be responsible for tracking adverse events in 
this study.  
The adverse event will be described with the following information: description of the 
event, outcome of the event, how long it lasted, relationship to study medications, whether the 
event required treatment or intervention, and the outcome.  
The definition of events is as follows:  
Mild – transient and mild in nature, with no treatment necessary.  
Moderate – some intervention and treatment necessary, but subject completely recovers.  
Severe – an event that results in hospitalization, disability, death or is life threatening.  
The investigator will state his opinion as to whether there is a reasonable possibility that 
the event or experience is related to the drug. 
 
10.2 Data and Safety Monitoring 
There will be no external Data and Safety monitoring committee for this study.  
 
11.0 STUDY WITHDRAWAL or DISONTINUATION 
11.1 Principal Investigator Initiated Withdrawal 
The principal investigator reserves the right to withdraw the subject from the study after 
they have provided informed consent, but before study completion. This could occur for one of 
many reasons, which include, but are not limited to: non-compliance with the protocol, a concern 
for subject safety, the availability of new knowledge that might affect continued participation in 
the study, or study termination. 
 
11.2. Study Subject-Initiated Withdrawal 
Subjects are free to withdraw from this study at any time. Withdrawal of consent or 
refusal to participate will not prejudice their health care. 
 
12.0 COMPENSATION 
Subjects will be compensated $25 for their time and inconvenience. 
 
13.0 PRIVACY & CONFIDENTIALITY ISSUES 
Protected Health Information will be used in this study. The investigators will comply 
with the patient privacy guidelines of Vanderbilt University Medical Center and the rules 
outlined by the Health Insurance Portability and Accountability Act (HIPAA). 
 

 
 
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The research team is comprised of experienced research nurses and research assistants 
who are aware of the importance of confidentiality of health information. Research records will 
be stored in a locked office. Digital records will be stored on password-protected 
computers/servers. Digital data files will be coded so that the subject name is not in the filename 
or other such identifiers.  
 
Every effort will be made to publish and present the data from this study. At no time will 
any subject be identified in any such publication. 
 
14.0 FOLLOW-UP AND RECORD RETENTION 
14.1 Follow-Up  
There will be no further study follow-up after the physiological breathing study is 
completed. 
 
14.2 Record Retention 
Study records will be kept for at least 7 years following the publication or presentation of 
the data collected as part of this study. 
 
15.0 Study Support 
 
Study costs will be funded from R01 HL102387. 
 
16.0 Reference List 
 
 
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 (16)  Rozanski A, Qureshi E, Bauman M, Reed G, Pillar G, Diamond GA. Peripheral arterial 
responses to treadmill exercise among healthy subjects and atherosclerotic patients. 
Circulation 2001 April 24;103(16):2084-9. 
 (17)  Meredith IT, Currie KE, Anderson TJ, Roddy MA, Ganz P, Creager MA. Postischemic 
vasodilation in human forearm is dependent on endothelium-derived nitric oxide. Am J 
Physiol 1996 April;270(4 Pt 2):H1435-H1440. 

 
 
Version Date: 5/28/14 
 
13
 (18)  Dakak N, Husain S, Mulcahy D, Andrews NP, Panza JA, Waclawiw M, Schenke W, 
Quyyumi AA. Contribution of nitric oxide to reactive hyperemia: impact of endothelial 
dysfunction. Hypertension 1998 July;32(1):9-15. 
 (19)  Higashi Y, Sasaki S, Nakagawa K, Matsuura H, Kajiyama G, Oshima T. A noninvasive 
measurement of reactive hyperemia that can be used to assess resistance artery 
endothelial function in humans. Am J Cardiol 2001 January 1;87(1):121-5, A9. 
 (20)  Wilkinson IB, Qasem A, McEniery CM, Webb DJ, Avolio AP, Cockcroft JR. Nitric 
oxide regulates local arterial distensibility in vivo. Circulation 2002 January 
15;105(2):213-7. 
 (21)  Noon JP, Haynes WG, Webb DJ, Shore AC. Local inhibition of nitric oxide generation in 
man reduces blood flow in finger pulp but not in hand dorsum skin. J Physiol 1996 
January 15;490 ( Pt 2):501-8. 
 (22)  Nohria A, Gerhard-Herman M, Creager MA, Hurley S, Mitra D, Ganz P. Role of nitric 
oxide in the regulation of digital pulse volume amplitude in humans. J Appl Physiol 2006 
August;101(2):545-8. 
 (23)  Thijssen DH, Black MA, Pyke KE, Padilla J, Atkinson G, Harris RA, Parker B, 
Widlansky ME, Tschakovsky ME, Green DJ. Assessment of flow-mediated dilation in 
humans: a methodological and physiological guideline. Am J Physiol Heart Circ Physiol 
2011 January;300(1):H2-12. 
 (24)  Deanfield J, Donald A, Ferri C, Giannattasio C, Halcox J, Halligan S, Lerman A, Mancia 
G, Oliver JJ, Pessina AC, Rizzoni D, Rossi GP, Salvetti A, Schiffrin EL, Taddei S, Webb 
DJ, Working Group on Endothelin and Endothelial Factors of the European Society of. 
Endothelial function and dysfunction. Part I: Methodological issues for assessment in the 
different vascular beds: a statement by the Working Group on Endothelin and Endothelial 
Factors of the European Society of Hypertension. J Hypertens 2005 January;23(1):7-17. 
 (25)  Bonetti PO, Pumper GM, Higano ST, Holmes DR, Jr., Kuvin JT, Lerman A. Noninvasive 
identification of patients with early coronary atherosclerosis by assessment of digital 
reactive hyperemia. J Am Coll Cardiol 2004 December 7;44(11):2137-41. 
 (26)  Dupont WD, Plummer WD. PS power and sample size program available for free on the 
Internet. Control Clin Trials 1997;18:274. 
 
 

Vanderbilt University Institutional Review Board 
Informed Consent Document for Research 
 
Principal Investigator:  Emily Garland, PhD 
    
Revision Date:  5/28/14 
Study Title:  A Pilot Study of the Effect of Dietary Sodium Intake on Assessments of Vascular Endothelium 
Institution/Hospital: Vanderbilt University 
 
1 of 4 
This informed consent applies to healthy persons.  
 
 
Name of participant: _________________________________________________________ Age: ___________ 
 
The following is given to you to tell you about this research study.  Please read this form with care and ask any questions you 
may have about this study.  Your questions will be answered.  Also, you will be given a copy of this consent form.   
 
You do not have to be in this research study. You can stop being in this study at any time.  If we learn something new that may affect the 
risks or benefits of this study, you will be told so that you can decide whether or not you still want to be in this study.    
 
     
1. What is the purpose of this study?  
 
You are being asked to take part in this research study because you are healthy and are taking part in another 
study (Dietary Salt in Postural Tachycardia Syndrome). We want to measure chemicals in your blood while you are 
on a very high salt or a very low salt diet. About 44 people will take part in this study. 
 
2. What will happen and how long will you be in the study? 
   
If you agree to be in this study, we will use information you have given us for other studies, and we will look at your 
medical record. We will also use information you have given us for the Dietary Salt in Postural Tachycardia 
Syndrome study (called the parent study.) 
 
On Day 6 of each phase of the parent study (there are two phases), we will study you either before you have eaten 
in the morning or at least 2 hours after you have eaten. We will take blood from your arm with a needle (about 1 
tablespoon in each time.)  
 
 
We will then ask you to lie down. We will place a blood pressure cuff on one arm and small probes on one finger on 
each of your hands. We will place soft sponge rings on either side of the probed fingers to keep them separated. 
The probes will measure your blood pressure. We will measure the diameter of the artery in your arm using 
ultrasound. Ultrasound involves putting a probe on your skin to get measurements. It is not invasive and does not 
cause pain. 
 
After 10 minutes, we will inflate the blood pressure cuff 60 points above the highest number on your normal blood 
pressure. The cuff will stay inflated for 5 minutes, and again measure your artery using ultrasound. We will then let 
the air out of the cuff.  
 
During this time, we will also place two cuffs on your left leg - one just above the calf and one just above the knee. 
A flexible cuff will be placed between these two cuffs and connected to a meter which will measure the amount of 
blood flow in the calf when the two cuffs above and below are inflated. You will then be allowed to lie quietly for 9 
minutes. When you have been at rest for 9 minutes, your blood pressure and calf blood flow will be measured for 
one minute. For this, we will inflate the blood pressure cuff on your lower leg to a pressure high enough to stop the 
blood flow. After 1 minute the cuff will be deflated, and your blood pressure and forearm blood flow will be recorded. 
We will then inflate the cuff placed on your upper leg to stop the blood flow of your leg for 5 minutes (like a 
tourniquet). At the end of this 5 minutes the cuff will be released, and we will repeat the measurements of blood 
pressure and calf blood flow for the next 3 minutes. 
 
We will insert a small tube (catheter) into a vein in your forearm. We will then slide a tiny wire into your vein to 
collect cells from the walls of your vein. We will do this three times. Then we will remove the small tube. 
Date of Approval:9/23/2014
Date of Expiration:9/22/2015

Vanderbilt University Institutional Review Board 
Informed Consent Document for Research 
 
Principal Investigator:  Emily Garland, PhD 
    
Revision Date:  5/28/14 
Study Title:  A Pilot Study of the Effect of Dietary Sodium Intake on Assessments of Vascular Endothelium 
Institution/Hospital: Vanderbilt University 
 
2 of 4 
 
 
This study will then be complete. The study will last about 2 hours on each study day. 
 
3. Costs to you if you take part in this study: 
 
 
If you agree to take part in this research study, you and/or your insurance will not have to pay for the tests and 
treatments that are being done only for research. 
For this study it includes the research only procedures noted in section 2 above. 
However, you are still responsible for paying for the usual care you would normally receive for the treatment of your 
illness. This includes treatments and tests you would need even if you were not in this study. These costs will be 
billed to you and/or your insurance.  
 
4. Side effects and risks that you can expect if you take part in this study:  
 
Inconveniences: It may be inconvenient to come to the CRC. 
 
Blood drawing and catheter in vein:  Drawing blood with a needle in a vein may be painful and may cause 
bruising, bleeding, or rarely, infection.  Some people may feel faint when having a needle put in their arm.    
 
Blood pressure cuff: Some may find it uncomfortable to hold their arms or legs with an inflated cuff placed around 
the forearm, finger, or thigh, in a mostly still position, or have the cuff inflated frequently. The finger probes may be 
tight and uncomfortable. 
 
5. Risks that are not known: 
 
None. 
 
6.  Payment in case you are injured because of this research study: 
 
If it is determined by Vanderbilt and the Investigator that an injury occurred as a direct result of the tests or 
treatments that are done for research, then you and/or your insurance will not have to pay for the cost of immediate 
medical care provided at Vanderbilt to treat the injury.  
 
There are no plans for Vanderbilt to pay for the costs of any additional care. There are no plans for Vanderbilt to 
give you money for the injury.  
 
7.  Good effects that might result from this study:  
 
a) The benefits to science and humankind that might result from this study. we may learn more about how the 
autonomic nervous system may affect people with POTS. This may lead to new treatments for this condition.  
b) The benefits you might get from being in this study. None. 
 
8.  Other treatments you could get if you decide not to be in this study: 
   
     This is not a treatment study.  You can choose not to be in this study, and nothing about your health care will change. 
 
 
 
Date of Approval:9/23/2014
Date of Expiration:9/22/2015

Vanderbilt University Institutional Review Board 
Informed Consent Document for Research 
 
Principal Investigator:  Emily Garland, PhD 
    
Revision Date:  5/28/14 
Study Title:  A Pilot Study of the Effect of Dietary Sodium Intake on Assessments of Vascular Endothelium 
Institution/Hospital: Vanderbilt University 
 
3 of 4 
9.  Payments for your time spent taking part in this study or expenses: 
 
You will be paid $25 for completing this study. You may choose to receive a check for this amount or a gift card for the 
same amount from Target, Walmart, or Amazon. 
 
10. Reasons why the study doctor may take you out of this study:   
 
You will be withdrawn from the study if the study doctors decide it is best for you. If the study doctors withdraw you from 
the study, you will be told the reason. 
 
11. What will happen if you decide to stop being in this study? 
 
If you decide to stop being part of the study, you should tell your study doctor. 
 
12. Who to call for any questions or in case you are injured: 
 
If you should have any questions about this research study or if you feel you have been hurt by being a part of this 
study, please feel free to contact Dr. Emily Garland at 615-936-1748 or the research nurse at 615-343-6862.D 
 
For additional information about giving consent or your rights as a person in this study, to discuss problems, concerns, 
and questions, or to offer input, please feel free to call the Vanderbilt University Institutional Review Board Office at 
(615) 322-2918 or toll free at (866) 224-8273. 
 
13. Confidentiality:   
 
All efforts, within reason, will be made to keep your personal information in your research record confidential but total 
confidentiality cannot be guaranteed. The study results will be kept in your research record for at least seven years after 
the study is over for as long as we need the information for the study. All the information on paper will be kept locked in 
a secure location. Any information kept in a computer will be through the Vanderbilt CRC data system, which has many 
safeguards. Only members of Dr. Garland’s research team will be able to see any of the information that would identify 
you. Any research data entered into your medical record will be kept as long as it is needed. 
 
 
14. Authorization to Use/Disclose Protected Health Information:  
 
All efforts, within reason, will be made to keep your protected health information (PHI) private. PHI is your health 
information that is, or has been gathered or kept by Vanderbilt as a result of your healthcare.  This includes data 
gathered for research studies that can be traced back to you.  Using or sharing (“disclosure”) such data must follow 
federal privacy rules. By signing the consent for this study, you are agreeing (“authorization”) to the uses and likely 
sharing of your PHI.  If you decide to be in this research study, you are also agreeing to let the study team use and 
share your PHI as described below.  
 
As part of the study, Dr. Garland and her study team may share the results of your study and/or non-study linked blood 
pressure, heart rate, and breathing tests, as well as parts of your medical record, to the groups named below. These 
groups may include people from the Federal Government Office for Human Research Protections, the Vanderbilt 
University Institutional Review Board, and the National Institutes of Health.  Federal privacy rules may not apply to 
these groups; they have their own rules and codes to assure that all efforts, within reason, will be made to keep your 
PHI private.  
 
Date of Approval:9/23/2014
Date of Expiration:9/22/2015

Vanderbilt University Institutional Review Board 
Informed Consent Document for Research 
 
Principal Investigator:  Emily Garland, PhD 
    
Revision Date:  5/28/14 
Study Title:  A Pilot Study of the Effect of Dietary Sodium Intake on Assessments of Vascular Endothelium 
Institution/Hospital: Vanderbilt University 
 
4 of 4 
The study results will be kept in your research record for at least six years after the study is finished.  At that time, the 
research data that has not been put in your medical record will be kept indefinitely. Any research data that has been put 
into your medical record will be kept for an unknown length of time. 
 
Unless told otherwise, your consent to use or share your PHI does not expire. If you change your mind, we ask that you 
contact Dr. Garland in writing and let her know that you withdraw your consent. Her mailing address is 
 
Dr. Emily Garland 
AA3228 Medical Center North 
1161 21st Avenue South 
Vanderbilt University 
Nashville, TN 37232-2195 
 
At that time, we will stop getting any more data about you.  But, the health data we stored before you withdrew your 
consent may still be used for reporting and research quality. 
 
 
If you decide not to take part in this research study, it will not affect your treatment, payment or enrollment in any 
health plans or affect your ability to get benefits. You will get a copy of this form after it is signed.  
 
 
 
STATEMENT BY PERSON AGREEING TO BE IN THIS STUDY 
 
I have read this consent form and the research study has been explained to me verbally.  All my questions 
have been answered, and I freely and voluntarily choose to take part in this study.    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date 
 
 
 
Signature of patient/volunteer 
 
 
 
 
 
Consent obtained by: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date 
 
 
 
Signature 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name and Title  
Date of Approval:9/23/2014
Date of Expiration:9/22/2015

Vanderbilt University Institutional Review Board 
Informed Consent Document for Research 
 
Principal Investigator:  Emily Garland, PhD 
 
Revision Date:  5/28/14 
Study Title:  A Pilot Study of the Effect of Dietary Sodium Intake on Assessments of Vascular Endothelium 
Institution/Hospital: Vanderbilt University 
 
 
1 of 4 
 
This informed consent applies to persons with postural tachycardia syndrome (POTS).  
 
 
Name of participant: _________________________________________________________ Age: ___________ 
 
The following is given to you to tell you about this research study.  Please read this form with care and ask any questions you 
may have about this study.  Your questions will be answered.  Also, you will be given a copy of this consent form.   
 
You do not have to be in this research study. You can stop being in this study at any time.  If we learn something new that may affect the 
risks or benefits of this study, you will be told so that you can decide whether or not you still want to be in this study.    
 
     
1. What is the purpose of this study?  
 
You are being asked to take part in this research study because you have postural tachycardia syndrome (POTS) 
and are taking part in another study (Dietary Salt in Postural Tachycardia Syndrome). We want to measure 
chemicals in your blood while you are on a very high salt or a very low salt diet. About 44 people will take part in 
this study. 
 
2. What will happen and how long will you be in the study? 
   
If you agree to be in this study, we will use information you have given us for other studies, and we will look at your 
medical record. We will also use information you have given us for the Dietary Salt in Postural Tachycardia 
Syndrome study (called the parent study.) 
 
On Day 6 of each phase of the parent study (there are two phases), we will study you either before you have eaten 
in the morning or at least 2 hours after you have eaten. We will take blood from your arm with a needle (about 1 
tablespoon in each time.)  
 
 
We will then ask you to lie down. We will place a blood pressure cuff on one arm and small probes on one finger on 
each of your hands. We will place soft sponge rings on either side of the probed fingers to keep them separated. 
The probes will measure your blood pressure. We will measure the diameter of the artery in your arm using 
ultrasound. Ultrasound involves putting a probe on your skin to get measurements. It is not invasive and does not 
cause pain. 
 
After 10 minutes, we will inflate the blood pressure cuff 60 points above the highest number on your normal blood 
pressure. The cuff will stay inflated for 5 minutes, and again measure your artery using ultrasound. We will then let 
the air out of the cuff.  
 
During this time, we will also place two cuffs on your left leg - one just above the calf and one just above the knee. 
A flexible cuff will be placed between these two cuffs and connected to a meter which will measure the amount of 
blood flow in the calf when the two cuffs above and below are inflated. You will then be allowed to lie quietly for 9 
minutes. When you have been at rest for 9 minutes, your blood pressure and calf blood flow will be measured for 
one minute. For this, we will inflate the blood pressure cuff on your lower leg to a pressure high enough to stop the 
blood flow. After 1 minute the cuff will be deflated, and your blood pressure and forearm blood flow will be recorded. 
We will then inflate the cuff placed on your upper leg to stop the blood flow of your leg for 5 minutes (like a 
tourniquet). At the end of this 5 minutes the cuff will be released, and we will repeat the measurements of blood 
pressure and calf blood flow for the next 3 minutes. 
 
Date of Approval:9/23/2014
Date of Expiration:9/22/2015

Vanderbilt University Institutional Review Board 
Informed Consent Document for Research 
 
Principal Investigator:  Emily Garland, PhD 
 
Revision Date:  5/28/14 
Study Title:  A Pilot Study of the Effect of Dietary Sodium Intake on Assessments of Vascular Endothelium 
Institution/Hospital: Vanderbilt University 
 
 
2 of 4 
 
We will insert a small tube (catheter) into a vein in your forearm. We will then slide a tiny wire into your vein to 
collect cells from the walls of your vein. We will do this three times. Then we will remove the small tube. 
 
 
This study will then be complete. The study will last about 2 hours on each study day. 
 
3. Costs to you if you take part in this study: 
 
 
If you agree to take part in this research study, you and/or your insurance will not have to pay for the tests and 
treatments that are being done only for research. 
For this study it includes the research only procedures noted in section 2 above. 
However, you are still responsible for paying for the usual care you would normally receive for the treatment of your 
illness. This includes treatments and tests you would need even if you were not in this study. These costs will be 
billed to you and/or your insurance.  
 
4. Side effects and risks that you can expect if you take part in this study:  
 
Inconveniences: It may be inconvenient to come to the CRC. 
 
Blood drawing and catheter in vein:  Drawing blood with a needle in a vein may be painful and may cause 
bruising, bleeding, or rarely, infection.  Some people may feel faint when having a needle put in their arm.    
 
Blood pressure cuff: Some may find it uncomfortable to hold their arms or legs with an inflated cuff placed around 
the forearm, finger, or thigh, in a mostly still position, or have the cuff inflated frequently. The finger probes may be 
tight and uncomfortable. 
 
5. Risks that are not known: 
 
None. 
 
6.  Payment in case you are injured because of this research study: 
 
If it is determined by Vanderbilt and the Investigator that an injury occurred as a direct result of the tests or 
treatments that are done for research, then you and/or your insurance will not have to pay for the cost of immediate 
medical care provided at Vanderbilt to treat the injury.  
 
There are no plans for Vanderbilt to pay for the costs of any additional care. There are no plans for Vanderbilt to 
give you money for the injury.  
 
7.  Good effects that might result from this study:  
 
a) The benefits to science and humankind that might result from this study. we may learn more about how the 
autonomic nervous system may affect people with POTS. This may lead to new treatments for this condition.  
b) The benefits you might get from being in this study. None. 
 
8.  Other treatments you could get if you decide not to be in this study: 
   
     This is not a treatment study.  You can choose not to be in this study, and nothing about your health care will change. 
Date of Approval:9/23/2014
Date of Expiration:9/22/2015

Vanderbilt University Institutional Review Board 
Informed Consent Document for Research 
 
Principal Investigator:  Emily Garland, PhD 
 
Revision Date:  5/28/14 
Study Title:  A Pilot Study of the Effect of Dietary Sodium Intake on Assessments of Vascular Endothelium 
Institution/Hospital: Vanderbilt University 
 
 
3 of 4 
 
9.  Payments for your time spent taking part in this study or expenses: 
 
You will be paid $25 for completing this study. You may choose to receive a check for this amount or a gift card for the 
same amount from Target, Walmart, or Amazon. 
 
10. Reasons why the study doctor may take you out of this study:   
 
You will be withdrawn from the study if the study doctors decide it is best for you. If the study doctors withdraw you from 
the study, you will be told the reason. 
 
11. What will happen if you decide to stop being in this study? 
 
If you decide to stop being part of the study, you should tell your study doctor. 
 
12. Who to call for any questions or in case you are injured: 
 
If you should have any questions about this research study or if you feel you have been hurt by being a part of this 
study, please feel free to contact Dr. Emily Garland at 615-936-1748 or the research nurse at 615-343-6862. 
 
For additional information about giving consent or your rights as a person in this study, to discuss problems, concerns, 
and questions, or to offer input, please feel free to call the Vanderbilt University Institutional Review Board Office at 
(615) 322-2918 or toll free at (866) 224-8273. 
 
13. Confidentiality:   
 
All efforts, within reason, will be made to keep your personal information in your research record confidential but total 
confidentiality cannot be guaranteed. The study results will be kept in your research record for at least seven years after 
the study is over for as long as we need the information for the study. All the information on paper will be kept locked in 
a secure location. Any information kept in a computer will be through the Vanderbilt CRC data system, which has many 
safeguards. Only members of Dr. Garland’s research team will be able to see any of the information that would identify 
you. Any research data entered into your medical record will be kept as long as it is needed. 
 
 
14. Authorization to Use/Disclose Protected Health Information:  
 
All efforts, within reason, will be made to keep your protected health information (PHI) private. PHI is your health 
information that is, or has been gathered or kept by Vanderbilt as a result of your healthcare.  This includes data 
gathered for research studies that can be traced back to you.  Using or sharing (“disclosure”) such data must follow 
federal privacy rules. By signing the consent for this study, you are agreeing (“authorization”) to the uses and likely 
sharing of your PHI.  If you decide to be in this research study, you are also agreeing to let the study team use and 
share your PHI as described below.  
 
As part of the study, Dr. Garland and her study team may share the results of your study and/or non-study linked blood 
pressure, heart rate, and breathing tests, as well as parts of your medical record, to the groups named below. These 
groups may include people from the Federal Government Office for Human Research Protections, the Vanderbilt 
University Institutional Review Board, and the National Institutes of Health.  Federal privacy rules may not apply to 
these groups; they have their own rules and codes to assure that all efforts, within reason, will be made to keep your 
PHI private.  
Date of Approval:9/23/2014
Date of Expiration:9/22/2015

Vanderbilt University Institutional Review Board 
Informed Consent Document for Research 
 
Principal Investigator:  Emily Garland, PhD 
 
Revision Date:  5/28/14 
Study Title:  A Pilot Study of the Effect of Dietary Sodium Intake on Assessments of Vascular Endothelium 
Institution/Hospital: Vanderbilt University 
 
 
4 of 4 
 
 
The study results will be kept in your research record for at least six years after the study is finished.  At that time, the 
research data that has not been put in your medical record will be kept indefinitely. Any research data that has been put 
into your medical record will be kept for an unknown length of time. 
 
Unless told otherwise, your consent to use or share your PHI does not expire. If you change your mind, we ask that you 
contact Dr. Garland in writing and let her know that you withdraw your consent. Her mailing address is 
 
Dr. Emily Garland 
AA3228 Medical Center North 
1161 21st Avenue South 
Vanderbilt University 
Nashville, TN 37232-2195 
 
At that time, we will stop getting any more data about you.  But, the health data we stored before you withdrew your 
consent may still be used for reporting and research quality. 
 
 
If you decide not to take part in this research study, it will not affect your treatment, payment or enrollment in any 
health plans or affect your ability to get benefits. You will get a copy of this form after it is signed.  
 
 
 
STATEMENT BY PERSON AGREEING TO BE IN THIS STUDY 
 
I have read this consent form and the research study has been explained to me verbally.  All my questions 
have been answered, and I freely and voluntarily choose to take part in this study.    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date 
 
 
 
Signature of patient/volunteer 
 
 
 
 
 
Consent obtained by: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date 
 
 
 
Signature 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name and Title  
Date of Approval:9/23/2014
Date of Expiration:9/22/2015