Renal Salt Handling in Postural Tachycardia Syndrome Following Dietary Dopa Administration

Early Phase 1

Completed

Conditions: Healthy Participants

Interventions: Dietary Supplement: Fava beans
Other: Fixed Sodium Diet

Registration Number: NCT01064739

Lead Sponsor: Vanderbilt University

Brief Summary: 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:

1. To determine the effect of dietary dopa sources on plasma and urinary catecholamines.

2. To investigate the capacity of botanical dopaminergic agents (fava beans) to induce natriuresis in a short term study.

3. 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 14

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Study Diet +/- fava beans	Fava beans	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).
Study Diet +/- fava beans	Fixed Sodium Diet	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).

Primary Outcome Measures

Name	Time	Method
Plasma Dopa 1 hr After Breakfast	Plasma samples collected 1 hour after breakfast on both study days.	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.
Urinary Dopa	4-8 hours after breakfast	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.
Urinary Sodium	4 to 8 hours after breakfast	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.

Secondary Outcome Measures

Name	Time	Method
Supine Systolic Blood Pressure	Supine-6 hours after breakfast on both study days.	Supine systolic blood pressure 6 hours after breakfast
Supine Heart Rate	6 hours after breakfast	Supine heart rate 6 hours after breakfast
Urinary Sodium	8-12 hours after breakfast	urinary sodium 8-12 hours after breakfast
Plasma Dopa 2 Hrs After Breakfast	Plasma samples collected 2 hours after breakfast on both study days.	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 Dopa 4 Hrs After Breakfast	Plasma samples collected 4 hours after breakfast on both study days.	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 Dopa 6 Hrs After Breakfast	Plasma samples collected 6 hours after breakfast on both study days.	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 Norepinephrine	6 hours after breakfast on both study days.	Plasma norepinephrine 6 hours after breakfast
Plasma Dopamine	Plasma samplesPlasma dopamine 6 hours after breakfast on both study days.	Plasma dopamine 6 hours after breakfast
Urinary Dopa	8-12 hours after breakfast	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.
Urinary Dopamine	8 to 12 hours after breakfast	Urinary dopamine excreted 8 to 12 hours after breakfast
Urinary Norepinephrine	8 to 12 hours after breakfast	Urinary norepinephrine excreted 8-12 hours after breakfast