- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01550315
Effect of Dietary Sodium Intake on Vascular Endothelium
A Pilot Study of the Effect of Dietary Sodium Intake on Assessments of Vascular Endothelium
Study Overview
Status
Conditions
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
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Tennessee
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Nashville, Tennessee, United States, 37232
- Vanderbilt University Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Non-Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: High Sodium - POTS & Controls
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.
|
Other Names:
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
Other Names:
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.
Other Names:
|
Other: Low Sodium Diet (POTS & Controls)
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. |
Other Names:
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
Other Names:
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
FMD (% Change)
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.
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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
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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.
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Collaborators and Investigators
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 111577
- R01HL102387 (U.S. NIH Grant/Contract)
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