Clinical trial NCT01064739: Renal Salt Handling in Postural Tachycardia Syndrome Following Dietary Dopa Administration
Official title: Renal Salt Handling in Postural Tachycardia Syndrome Following Dietary Dopa Administration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Healthy Participants
Keywords: Healthy Volunteers
Fava bean consumption
L-Dopa content in Fava Beans
Sodium
Potassium
Electrolyte Balance
Natriuresis
Lead sponsor: Vanderbilt University
Sponsor class: OTHER
First posted: 2010-02-08
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP

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.

Eligibility criteria: 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

Primary outcomes:
measure: Plasma Dopa 1 hr After Breakfast
timeFrame: Plasma samples collected 1 hour after breakfast on both study days.
measure: Urinary Dopa
timeFrame: 4-8 hours after breakfast
measure: Urinary Sodium
timeFrame: 4 to 8 hours after breakfast
Secondary outcomes:
measure: Plasma Dopa 2 Hrs After Breakfast
timeFrame: Plasma samples collected 2 hours after breakfast on both study days.
measure: Plasma Dopa 4 Hrs After Breakfast
timeFrame: Plasma samples collected 4 hours after breakfast on both study days.
measure: Plasma Dopa 6 Hrs After Breakfast
timeFrame: Plasma samples collected 6 hours after breakfast on both study days.
measure: Plasma Norepinephrine
timeFrame: 1 hour after breakfast on both study days.
measure: Plasma Norepinephrine
timeFrame: 2 hours after breakfast on both study days.
measure: Plasma Norepinephrine
timeFrame: 4 hours after breakfast on both study days.
measure: Plasma Norepinephrine
timeFrame: 6 hours after breakfast on both study days.
measure: Plasma Dopamine
timeFrame: 1 hour after breakfast
measure: Plasma Dopamine
timeFrame: 2 hours after breakfast on both study days.
measure: Plasma Dopamine
timeFrame: 4 hours after breakfast on both study days.
measure: Plasma Dopamine
timeFrame: Plasma samplesPlasma dopamine 6 hours after breakfast on both study days.
measure: Urinary Dopa
timeFrame: 0-4 hours after breakfast
measure: Urinary Dopa
timeFrame: 8-12 hours after breakfast
measure: Urinary Dopamine
timeFrame: 0 to 4 hours after breakfast
measure: Urinary Dopamine
timeFrame: 4 to 8 hours after breakfast
measure: Urinary Dopamine
timeFrame: 8 to 12 hours after breakfast
measure: Urinary Norepinephrine
timeFrame: 0 to 4 hours after breakfast
measure: Urinary Norepinephrine
timeFrame: 4 to 8 hours after breakfast
measure: Urinary Norepinephrine
timeFrame: 8 to 12 hours after breakfast
measure: Supine Systolic Blood Pressure
timeFrame: Supine-6 hours after breakfast on both study days.
measure: Supine Heart Rate
timeFrame: 6 hours after breakfast
measure: Urinary Sodium
timeFrame: 0-4 hours after breakfast
measure: Urinary Sodium
timeFrame: 8-12 hours after breakfast
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Clinical Research Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Emily M Garland, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.