Renal Salt Handling in Postural Tachycardia Syndrome Following Dietary Dopa Administration

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.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Dietary supplement: Fava beans; Other: Fixed Sodium Diet

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232-2195
      • Vanderbilt University Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Study Diet +/- 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).

Dietary supplement: Fava beans; 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; Other: Fixed Sodium Diet; Fixed sodium low monoamine diet

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Vanderbilt University
• Investigators: Principal Investigator: Emily M Garland, PhD, Vanderbilt University Medical Center

Publications and helpful links

General Publications

• Garland EM, Cesar TS, Lonce S, Ferguson MC, Robertson D. An increase in renal dopamine does not stimulate natriuresis after fava bean ingestion. Am J Clin Nutr. 2013 May;97(5):1144-50. doi: 10.3945/ajcn.112.048470. Epub 2013 Apr 3.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: February 5, 2010
• First Submitted That Met QC Criteria: February 5, 2010
• First Posted (Estimate): February 8, 2010

Study Record Updates

• Last Update Posted (Estimate): May 26, 2016
• Last Update Submitted That Met QC Criteria: April 26, 2016
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: Healthy Volunteers; Fava bean consumption; L-Dopa content in Fava Beans; Sodium; Potassium; Electrolyte Balance; Natriuresis
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Nervous System Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Autonomic Nervous System Diseases; Primary Dysautonomias; Orthostatic Intolerance; Tachycardia; Postural Orthostatic Tachycardia Syndrome
• Other Study ID Numbers: PN 1767

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No