Renal Salt Handling in Postural Tachycardia Syndrome Following Dietary Dopa Administration

Study Overview
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Brief Summary
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The purpose of this study is to learn how plants can play a role in gain/loss of sodium in the urine and in the regulation of blood pressure. Dopamine is a chemical mostly present in the brain and kidneys which assists in regulation of the body's salts (sodium and potassium). Fava beans contain a lot of the chemical that increases the production of dopamine by the kidneys. The purpose of these studies is to characterize the diuretic effects of dietary catecholamine sources in healthy individuals. Specific aims are: To determine the effect of dietary dopa sources on plasma and urinary catecholamines. To investigate the capacity of botanical dopaminergic agents (fava beans) to induce natriuresis in a short term study. To provide preliminary data on the effects of dietary dopa on heart rate and blood pressure. In these studies, we will test the null hypothesis (Ho) that urinary sodium excretion will not differ in healthy volunteers after consumption of a fixed-sodium study diet and the study diet plus fava beans.

Detailed Description
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Fava beans are a broad bean, with potential clinical relevance in Parkinson's patients since they contain high levels of the dopamine precursor, dihydroxyphenylalanine (dopa).In addition to the central nervous system functions of dopamine that are compromised in Parkinson's disease, renal dopamine has vasodilatory and natriuretic activity. Elevated urinary dopamine, however, does not consistently correlate with increased urinary sodium excretion, and there are conflicting opinions over the conditions under which renal dopamine might regulate sodium balance.The goal of our study was to clarify the natriuretic effect of fava beans, obtained from a source that serves patients with Parkinson's disease. Catechol and sodium data were compared in healthy volunteers using a longitudinal design in which all participants consumed a fixed sodium study diet on day 1 and the fixed sodium diet plus fava beans on day 2. Blood was sampled at 1, 2, 4 and 6 hours after breakfast, and three consecutive 4-hr urine samples were collected. Postural tachycardia syndrome (POTS) is the most common form of orthostatic intolerance, affecting an estimated 500,000 Americans, principally young women. POTS refers to an excessive increase in heart rate (>30 beats per minute) on standing in the absence of orthostatic hypotension. Previous findings by the Robertson/Garland research group suggest that mechanisms involved in orthostatic and absolute volume regulation contribute to POTS pathophysiology. A follow-up study might compare the influences of diet in patients with POTS and healthy volunteers.

Official Title
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Renal Salt Handling in Postural Tachycardia Syndrome Following Dietary Dopa Administration

Conditions
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Healthy Participants

Intervention / Treatment
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* Dietary Supplement: Fava beans
* Other: Fixed Sodium Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-smoking Free of medications with the potential to influence BP Age between 18-60 years Male and female subjects are eligible Able and willing to provide informed consent Exclusion Criteria: Significant cardiovascular, pulmonary, hepatic, or hematological disease by history or screening results Positive urine b-hcg pregnancy test Evidence of cardiac structural disease (by clinical examination or prior echocardiogram) Hypertension defined as a BP>145/95 (off medications) or need for antihypertensive medications Evidence of significant conduction system delay (QRS duration >120 ms) on electrocardiogram Inability to give, or withdraw, informed consent Other factors which in the investigator's opinion would prevent the subject from completing the protocol Food allergies to favas or other dietary dopa sources selected Parkinson's Disease Diagnosis of Glucose-6-Phosphate Dehydrogenase (G6P) Deficiency or Individuals from the Mediterranean with family history of G6PD. Prolonged QT interval on ECG> 480 13. Familial history of sudden cardiac death

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Diet +/- fava beans<br>Participants underwent testing while on a methylxanthine-free diet providing 150 mEq sodium and 75 mEq potassium per day. The study involved a longitudinal design where the participants served as their own controls. Subjects consumed the standard fixed sodium diet on study day one. On study day two, participants ate 100 g of puréed fava beans and pods with study diet at breakfast (0800hr) and lunch (1200hr). | Dietary Supplement: Fava beans<br>* Participants will receive 100g of fresh fava beans for breakfast and lunch on one study day and prior to this study day will be restricted to a fixed sodium low monoamine diet<br>Other: Fixed Sodium Diet<br>* Fixed sodium low monoamine diet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Dopa 1 hr After Breakfast | Subjects consumed the standard fixed sodium diet for at least two days prior to study and on study day one during an inpatient stay in the Vanderbilt Clinical Research Center. On study day two, participants ate 100 g of puréed fava beans and pods with study diet at breakfast (0800hr) and lunch (1200hr). Blood was sampled for catechol assays before and at 1, 2, 4 and 6 hours after breakfast. Plasma dopa 1 hour after breakfast was specified as a primary outcome. Other catechols (dihydroxyphenylglycol, norepinephrine, epinephrine, dopamine, dihydroxyphenylacetic acid) and other time points (2, 3, 4, 6hr after breakfast) are non-primary outcomes. | Plasma samples collected 1 hour after breakfast on both study days. | 
| Urinary Dopa | Urinary dopa excreted 4-8 hours after breakfast was specified as a primary outcome. Other catechols (dihydroxyphenylglycol, norepinephrine, epinephrine, dopamine, dihydroxyphenylacetic acid) and other time points (0-4 hr, 8-12 hr after breakfast) are non-primary outcomes. | 4-8 hours after breakfast | 
| Urinary Sodium | Urinary sodium excreted 4-8 hours after breakfast was designated as a primary outcome. Other urine samples (0-4 hr, 8-12 hr after breakfast) are considered as non-primary outcomes. | 4 to 8 hours after breakfast | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Dopa 2 Hrs After Breakfast | Subjects consumed the standard fixed sodium diet for at least two days prior to study and on study day one during an inpatient stay in the Vanderbilt Clinical Research Center. On study day two, participants ate 100 g of puréed fava beans and pods with study diet at breakfast (0800hr) and lunch (1200hr). Blood was sampled for catechol assays before and at 1, 2, 4 and 6 hours after breakfast. Plasma dopa 1 hour after breakfast was specified as a primary outcome. Other catechols (dihydroxyphenylglycol, norepinephrine, epinephrine, dopamine, dihydroxyphenylacetic acid) and other time points (2, 3, 4, 6hr after breakfast) are non-primary outcomes. | Plasma samples collected 2 hours after breakfast on both study days. | 
| Plasma Dopa 4 Hrs After Breakfast | Subjects consumed the standard fixed sodium diet for at least two days prior to study and on study day one during an inpatient stay in the Vanderbilt Clinical Research Center. On study day two, participants ate 100 g of puréed fava beans and pods with study diet at breakfast (0800hr) and lunch (1200hr). Blood was sampled for catechol assays before and at 1, 2, 4 and 6 hours after breakfast. Plasma dopa 1 hour after breakfast was specified as a primary outcome. Other catechols (dihydroxyphenylglycol, norepinephrine, epinephrine, dopamine, dihydroxyphenylacetic acid) and other time points (2, 3, 4, 6hr after breakfast) are non-primary outcomes. | Plasma samples collected 4 hours after breakfast on both study days. | 
| Plasma Dopa 6 Hrs After Breakfast | Subjects consumed the standard fixed sodium diet for at least two days prior to study and on study day one during an inpatient stay in the Vanderbilt Clinical Research Center. On study day two, participants ate 100 g of puréed fava beans and pods with study diet at breakfast (0800hr) and lunch (1200hr). Blood was sampled for catechol assays before and at 1, 2, 4 and 6 hours after breakfast. Plasma dopa 1 hour after breakfast was specified as a primary outcome. Other catechols (dihydroxyphenylglycol, norepinephrine, epinephrine, dopamine, dihydroxyphenylacetic acid) and other time points (2, 3, 4, 6hr after breakfast) are non-primary outcomes. | Plasma samples collected 6 hours after breakfast on both study days. | 
| Plasma Norepinephrine | Plasma norepinephrine 1 hour after breakfast | 1 hour after breakfast on both study days. | 
| Plasma Norepinephrine | Plasma norepinephrine 2 hours after breakfast | 2 hours after breakfast on both study days. | 
| Plasma Norepinephrine | Plasma norepinephrine 4 hours after breakfast | 4 hours after breakfast on both study days. | 
| Plasma Norepinephrine | Plasma norepinephrine 6 hours after breakfast | 6 hours after breakfast on both study days. | 
| Plasma Dopamine | Plasma dopamine 1 hour after breakfast | 1 hour after breakfast | 
| Plasma Dopamine | Plasma dopamine 2 hours after breakfast | 2 hours after breakfast on both study days. | 
| Plasma Dopamine | Plasma dopamine 4 hours after breakfast | 4 hours after breakfast on both study days. | 
| Plasma Dopamine | Plasma dopamine 6 hours after breakfast | Plasma samplesPlasma dopamine 6 hours after breakfast on both study days. | 
| Urinary Dopa | Urinary dopa excreted 4-8 hours after breakfast was specified as a primary outcome. Other time points (0-4 hr, 8-12 hr after breakfast) are non-primary outcomes. | 0-4 hours after breakfast | 
| Urinary Dopa | Urinary dopa excreted 4-8 hours after breakfast was specified as a primary outcome. Other time points (0-4 hr, 8-12 hr after breakfast) are non-primary outcomes. | 8-12 hours after breakfast | 
| Urinary Dopamine | Urinary dopamine excreted 0 to 4 hours after breakfast | 0 to 4 hours after breakfast | 
| Urinary Dopamine | Urinary dopamine excreted 4 to 8 hours after breakfast | 4 to 8 hours after breakfast | 
| Urinary Dopamine | Urinary dopamine excreted 8 to 12 hours after breakfast | 8 to 12 hours after breakfast | 
| Urinary Norepinephrine | Urinary norepinephrine excreted 0-4 hours after breakfast | 0 to 4 hours after breakfast | 
| Urinary Norepinephrine | Urinary norepinephrine excreted 4-8 hours after breakfast | 4 to 8 hours after breakfast | 
| Urinary Norepinephrine | Urinary norepinephrine excreted 8-12 hours after breakfast | 8 to 12 hours after breakfast | 
| Supine Systolic Blood Pressure | Supine systolic blood pressure 6 hours after breakfast | Supine-6 hours after breakfast on both study days. | 
| Supine Heart Rate | Supine heart rate 6 hours after breakfast | 6 hours after breakfast | 
| Urinary Sodium | Urinary sodium excreted 0-4 hours after breakfast. | 0-4 hours after breakfast | 
| Urinary Sodium | urinary sodium 8-12 hours after breakfast | 8-12 hours after breakfast | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fava bean consumption, L-Dopa content in Fava Beans, Sodium, Potassium, Healthy Volunteers, Electrolyte Balance, Natriuresis