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Effect of Dietary Sodium Intake on Vascular Endothelium

Primary Purpose

Postural Tachycardia Syndrome (POTS)

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Pulsitile Arterial Tonometry (PAT) Protocol

Calf Blood Flow in Reactive Hyperemia (CBF-RH)

Evaluation of Forearm-Mediated Dilation

About this trial

This is an interventional basic science trial for Postural Tachycardia Syndrome (POTS) focused on measuring POTS, endothelial function, high salt vs low salt diet, PAT protocol, Calf blood flow, forearm mediated dilation

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Subjects will be enrolled in the parent study "Dietary Salt in Postural Tachcyardia Syndrome" funded by R01 HL102387 Postural Tachycardia Syndrome
Diagnosed with postural tachycardia syndrome by the Vanderbilt Autonomic Dysfunction Center
Subjects will be enrolled in the parent study "Dietary Salt in Postural Tachcyardia Syndrome" funded by R01 HL102387
Postural Tachycardia Syndrome
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
Healthy, non-obese, non-smokers without orthostatic tachycardia
Selected to match profiles of POTS patients (gender, age)
Not using vasoactive medication
Age between 18-60 years
Male and female subjects are eligible.
Able and willing to provide informed consent

Exclusion Criteria:

Overt cause for postural tachycardia (such as acute dehydration)
Inability to give, or withdrawal of, informed consent
Pregnant
Other factors which in the investigator's opinion would prevent the subject from completing the protocol.

Sites / Locations

Vanderbilt University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Other

Arm Label

High Sodium - POTS & Controls

Low Sodium Diet (POTS & Controls)

Arm Description

Subjects will receive a high sodium diet for 4-5 days prior to study day. Procedures include: blood work, urine collection, Pulsitile Arterial Tonometry (PAT), PAT analysis, Calf Blood Flow in Reactive Hyperemia (CBF-RH), & evaluation of forearm-mediated dilation.

Participants will consume a very low sodium diet (10 mEq/day) for 4-5 days prior to study day. Procedures include: blood work, urine collection, Pulsitile Arterial Tonometry (PAT), PAT analysis, Calf Blood Flow in Reactive Hyperemia (CBF-RH), & evaluation of forearm-mediated dilation.

Outcomes

Primary Outcome Measures

FMD (% Change)

The primary analysis will involve a non-parametric, paired, Signed Rank test of flow mediated dilation (FMD) between all subjects (POTS & control subjects) on the high sodium diet vs low sodium diet

Secondary Outcome Measures

Full Information

NCT ID

NCT01550315

First Posted

March 2, 2012

Last Updated

December 7, 2021

Sponsor

Vanderbilt University Medical Center

Collaborators

National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)

1. Study Identification

Unique Protocol Identification Number

NCT01550315

Brief Title

Effect of Dietary Sodium Intake on Vascular Endothelium

Official Title

A Pilot Study of the Effect of Dietary Sodium Intake on Assessments of Vascular Endothelium

Study Type

Interventional

2. Study Status

Record Verification Date

December 2021

Overall Recruitment Status

Completed

Study Start Date

April 2012 (undefined)

Primary Completion Date

December 2020 (Actual)

Study Completion Date

September 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Vanderbilt University Medical Center

Collaborators

National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The investigators 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. The investigators will compare patients with postural orthostatic tachycardia (POTS) to healthy control subjects.

Detailed Description

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. Dietary success will be assessed using a 24h urine for sodium and creatinine as a part of the parent study. 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) aliquots (future analysis) Pulsitile Arterial Tonometry (PAT) Protocol Calf Blood Flow in Reactive Hyperemia (CBF-RH) - venous occlusion plethysmography Evaluation of Forearm-Mediated Dilation

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Postural Tachycardia Syndrome (POTS)

Keywords

POTS, endothelial function, high salt vs low salt diet, PAT protocol, Calf blood flow, forearm mediated dilation

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

27 (Actual)

8. Arms, Groups, and Interventions

Arm Title

High Sodium - POTS & Controls

Arm Type

Active Comparator

Arm Description

Arm Title

Low Sodium Diet (POTS & Controls)

Arm Type

Other

Arm Description

Intervention Type

Procedure

Intervention Name(s)

Pulsitile Arterial Tonometry (PAT) Protocol

Other Intervention Name(s)

EndoPat

Intervention Description

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.

Intervention Type

Device

Intervention Name(s)

Calf Blood Flow in Reactive Hyperemia (CBF-RH)

Other Intervention Name(s)

Hokansan strain guage venous plethysmography

Intervention Description

Calf blood flow (CBF) will be determined using venous occlusion plethysmography and calibrated mercury strain-gauges 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 8 seconds intervals, while monitoring the change in resistance in the system, pressure inside the measuring cuff, and 5-10 determinations are performed

Intervention Type

Device

Intervention Name(s)

Evaluation of Forearm-Mediated Dilation

Other Intervention Name(s)

Ultrasound

Intervention Description

The arm will be kept extended and immobilized at heart level. Brachial artery diameter will be measured using a high resolution ultrasonography using a linear array probe with a 5 to 17 MHz frequency range. 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.

Primary Outcome Measure Information:

Title

FMD (% Change)

Description

The primary analysis will involve a non-parametric, paired, Signed Rank test of flow mediated dilation (FMD) between all subjects (POTS & control subjects) on the high sodium diet vs low sodium diet

Time Frame

FMD was assessed on the morning of day 7, after 6 days of being on either a high salt diet or a low salt diet.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subjects will be enrolled in the parent study "Dietary Salt in Postural Tachcyardia Syndrome" funded by R01 HL102387 Postural Tachycardia Syndrome Diagnosed with postural tachycardia syndrome by the Vanderbilt Autonomic Dysfunction Center Subjects will be enrolled in the parent study "Dietary Salt in Postural Tachcyardia Syndrome" funded by R01 HL102387 Postural Tachycardia Syndrome 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 Healthy, non-obese, non-smokers without orthostatic tachycardia Selected to match profiles of POTS patients (gender, age) Not using vasoactive medication Age between 18-60 years Male and female subjects are eligible. Able and willing to provide informed consent Exclusion Criteria: Overt cause for postural tachycardia (such as acute dehydration) Inability to give, or withdrawal of, informed consent Pregnant Other factors which in the investigator's opinion would prevent the subject from completing the protocol.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Satish R Raj, MD MSCI

Organizational Affiliation

Vanderbilt University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Vanderbilt University Medical Center

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

9396430

Citation

Clarkson P, Celermajer DS, Powe AJ, Donald AE, Henry RM, Deanfield JE. Endothelium-dependent dilatation is impaired in young healthy subjects with a family history of premature coronary disease. Circulation. 1997 Nov 18;96(10):3378-83. doi: 10.1161/01.cir.96.10.3378.

Results Reference

background

PubMed Identifier

11345360

Citation

Al Suwaidi J, Higano ST, Holmes DR Jr, Lennon R, Lerman A. Obesity is independently associated with coronary endothelial dysfunction in patients with normal or mildly diseased coronary arteries. J Am Coll Cardiol. 2001 May;37(6):1523-8. doi: 10.1016/s0735-1097(01)01212-8.

Results Reference

background

PubMed Identifier

9799202

Citation

Boger RH, Bode-Boger SM, Szuba A, Tsao PS, Chan JR, Tangphao O, Blaschke TF, Cooke JP. Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia. Circulation. 1998 Nov 3;98(18):1842-7. doi: 10.1161/01.cir.98.18.1842.

Results Reference

background

PubMed Identifier

8417838

Citation

Mangin EL Jr, Kugiyama K, Nguy JH, Kerns SA, Henry PD. Effects of lysolipids and oxidatively modified low density lipoprotein on endothelium-dependent relaxation of rabbit aorta. Circ Res. 1993 Jan;72(1):161-6. doi: 10.1161/01.res.72.1.161.

Results Reference

background

PubMed Identifier

10725285

Citation

Vergnani L, Hatrik S, Ricci F, Passaro A, Manzoli N, Zuliani G, Brovkovych V, Fellin R, Malinski T. Effect of native and oxidized low-density lipoprotein on endothelial nitric oxide and superoxide production : key role of L-arginine availability. Circulation. 2000 Mar 21;101(11):1261-6. doi: 10.1161/01.cir.101.11.1261.

Results Reference

background

PubMed Identifier

10811593

Citation

Landmesser U, Merten R, Spiekermann S, Buttner K, Drexler H, Hornig B. Vascular extracellular superoxide dismutase activity in patients with coronary artery disease: relation to endothelium-dependent vasodilation. Circulation. 2000 May 16;101(19):2264-70. doi: 10.1161/01.cir.101.19.2264.

Results Reference

background

PubMed Identifier

7706483

Citation

Quyyumi AA, Dakak N, Andrews NP, Husain S, Arora S, Gilligan DM, Panza JA, Cannon RO 3rd. Nitric oxide activity in the human coronary circulation. Impact of risk factors for coronary atherosclerosis. J Clin Invest. 1995 Apr;95(4):1747-55. doi: 10.1172/JCI117852.

Results Reference

background

PubMed Identifier

21233236

Citation

Appel LJ, Frohlich ED, Hall JE, Pearson TA, Sacco RL, Seals DR, Sacks FM, Smith SC Jr, Vafiadis DK, Van Horn LV. The importance of population-wide sodium reduction as a means to prevent cardiovascular disease and stroke: a call to action from the American Heart Association. Circulation. 2011 Mar 15;123(10):1138-43. doi: 10.1161/CIR.0b013e31820d0793. Epub 2011 Jan 13. No abstract available.

Results Reference

background

PubMed Identifier

15788708

Citation

Meneton P, Jeunemaitre X, de Wardener HE, MacGregor GA. Links between dietary salt intake, renal salt handling, blood pressure, and cardiovascular diseases. Physiol Rev. 2005 Apr;85(2):679-715. doi: 10.1152/physrev.00056.2003.

Results Reference

background

PubMed Identifier

13582981

Citation

MENEELY GR, BALL CO. Experimental epidemiology of chronic sodium chloride toxicity and the protective effect of potassium chloride. Am J Med. 1958 Nov;25(5):713-25. doi: 10.1016/0002-9343(58)90009-3. No abstract available.

Results Reference

background

PubMed Identifier

19934192

Citation

Strazzullo P, D'Elia L, Kandala NB, Cappuccio FP. Salt intake, stroke, and cardiovascular disease: meta-analysis of prospective studies. BMJ. 2009 Nov 24;339:b4567. doi: 10.1136/bmj.b4567.

Results Reference

background

PubMed Identifier

12544447

Citation

Dishy V, Sofowora GG, Imamura H, Nishimi Y, Xie HG, Wood AJ, Stein CM. Nitric oxide production decreases after salt loading but is not related to blood pressure changes or nitric oxide-mediated vascular responses. J Hypertens. 2003 Jan;21(1):153-7. doi: 10.1097/00004872-200301000-00025.

Results Reference

background

PubMed Identifier

10694524

Citation

Fujiwara N, Osanai T, Kamada T, Katoh T, Takahashi K, Okumura K. Study on the relationship between plasma nitrite and nitrate level and salt sensitivity in human hypertension : modulation of nitric oxide synthesis by salt intake. Circulation. 2000 Feb 29;101(8):856-61. doi: 10.1161/01.cir.101.8.856.

Results Reference

background

PubMed Identifier

12851627

Citation

Kuvin JT, Patel AR, Sliney KA, Pandian NG, Sheffy J, Schnall RP, Karas RH, Udelson JE. Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude. Am Heart J. 2003 Jul;146(1):168-74. doi: 10.1016/S0002-8703(03)00094-2.

Results Reference

background

PubMed Identifier

11319199

Citation

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 Apr 24;103(16):2084-9. doi: 10.1161/01.cir.103.16.2084.

Results Reference

background

PubMed Identifier

8967386

Citation

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 Apr;270(4 Pt 2):H1435-40. doi: 10.1152/ajpheart.1996.270.4.H1435.

Results Reference

background

PubMed Identifier

9674631

Citation

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 Jul;32(1):9-15. doi: 10.1161/01.hyp.32.1.9.

Results Reference

background

PubMed Identifier

11137850

Citation

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 Jan 1;87(1):121-5, A9. doi: 10.1016/s0002-9149(00)01288-1.

Results Reference

background

PubMed Identifier

11790703

Citation

Wilkinson IB, Qasem A, McEniery CM, Webb DJ, Avolio AP, Cockcroft JR. Nitric oxide regulates local arterial distensibility in vivo. Circulation. 2002 Jan 15;105(2):213-7. doi: 10.1161/hc0202.101970.

Results Reference

background

PubMed Identifier

8821146

Citation

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 Jan 15;490 ( Pt 2)(Pt 2):501-8. doi: 10.1113/jphysiol.1996.sp021161.

Results Reference

background

PubMed Identifier

16614356

Citation

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 (1985). 2006 Aug;101(2):545-8. doi: 10.1152/japplphysiol.01285.2005. Epub 2006 Apr 13.

Results Reference

background

PubMed Identifier

20952670

Citation

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 Jan;300(1):H2-12. doi: 10.1152/ajpheart.00471.2010. Epub 2010 Oct 15.

Results Reference

background

PubMed Identifier

15643116

Citation

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 Hypertension. 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 Jan;23(1):7-17. doi: 10.1097/00004872-200501000-00004.

Results Reference

background

PubMed Identifier

15582310

Citation

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 Dec 7;44(11):2137-41. doi: 10.1016/j.jacc.2004.08.062.

Results Reference

background

PubMed Identifier

21293325

Citation

Centers for Disease Control and Prevention (CDC). Vital signs: prevalence, treatment, and control of hypertension--United States, 1999-2002 and 2005-2008. MMWR Morb Mortal Wkly Rep. 2011 Feb 4;60(4):103-8.

Results Reference

background

PubMed Identifier

33689063

Citation

Smith EC, Celedonio J, Nwazue VC, Garland EM, Paranjape SY, Chopoorian AH, Wahba A, Biaggioni I, Black B, Shibao CA, Diedrich A, Okamoto LE, Raj SR, Gamboa A. High-sodium diet does not worsen endothelial function in female patients with postural tachycardia syndrome. Clin Auton Res. 2021 Aug;31(4):563-571. doi: 10.1007/s10286-021-00772-y. Epub 2021 Mar 10.

Results Reference

derived

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Effect of Dietary Sodium Intake on Vascular Endothelium

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