Renal Salt Handling in Postural Tachycardia Syndrome Following Dietary Dopa Administration

Healthy Volunteers Clinical Trial

Official title:

Renal Salt Handling in Postural Tachycardia Syndrome Following Dietary Dopa Administration

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01064739
• Other study ID #: PN 1767
• Status: Completed
• Phase: Phase 0
• First received: February 5, 2010
• Last updated: August 1, 2013
• Start date: January 2007
• Est. completion date: December 2012

Study information

• Verified date: August 2013
• Source: Vanderbilt University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: December 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Healthy Volunteers
• Postural Orthostatic Tachycardia Syndrome
• Tachycardia

Intervention

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

Locations

Country	Name	City	State
United States	Vanderbilt University Clinical Research Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Primary	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	No
Primary	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	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	Plasma Norepinephrine	Plasma norepinephrine 1 hour after breakfast	1 hour after breakfast on both study days.	No
Secondary	Plasma Norepinephrine	Plasma norepinephrine 2 hours after breakfast	2 hours after breakfast on both study days.	No
Secondary	Plasma Norepinephrine	Plasma norepinephrine 4 hours after breakfast	4 hours after breakfast on both study days.	No
Secondary	Plasma Norepinephrine	Plasma norepinephrine 6 hours after breakfast	6 hours after breakfast on both study days.	No
Secondary	Plasma Dopamine	Plasma dopamine 1 hour after breakfast	1 hour after breakfast	No
Secondary	Plasma Dopamine	Plasma dopamine 2 hours after breakfast	2 hours after breakfast on both study days.	No
Secondary	Plasma Dopamine	Plasma dopamine 4 hours after breakfast	4 hours after breakfast on both study days.	No
Secondary	Plasma Dopamine	Plasma dopamine 6 hours after breakfast	Plasma samplesPlasma dopamine 6 hours after breakfast on both study days.	No
Secondary	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	No
Secondary	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	No
Secondary	Urinary Dopamine	Urinary dopamine excreted 0 to 4 hours after breakfast	0 to 4 hours after breakfast	No
Secondary	Urinary Dopamine	Urinary dopamine excreted 4 to 8 hours after breakfast	4 to 8 hours after breakfast	No
Secondary	Urinary Dopamine	Urinary dopamine excreted 8 to 12 hours after breakfast	8 to 12 hours after breakfast	No
Secondary	Urinary Norepinephrine	Urinary norepinephrine excreted 0-4 hours after breakfast	0 to 4 hours after breakfast	No
Secondary	Urinary Norepinephrine	Urinary norepinephrine excreted 4-8 hours after breakfast	4 to 8 hours after breakfast	No
Secondary	Urinary Norepinephrine	Urinary norepinephrine excreted 8-12 hours after breakfast	8 to 12 hours after breakfast	No
Secondary	Supine Systolic Blood Pressure	Supine systolic blood pressure 6 hours after breakfast	Supine-6 hours after breakfast on both study days.	No
Secondary	Supine Heart Rate	Supine heart rate 6 hours after breakfast	6 hours after breakfast	No
Secondary	Urinary Sodium	Urinary sodium excreted 0-4 hours after breakfast.	0-4 hours after breakfast	No
Secondary	Urinary Sodium	urinary sodium 8-12 hours after breakfast	8-12 hours after breakfast	No