Peripheral Dopamine in Postural Tachycardia Syndrome

NCT00685919 | Completed Phase 2 Results

• 2 other identifiers: 101499HL071784-05A1
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the proposed research is to determine how changes in kidney dopamine (DA) activity influence urinary sodium excretion. We will decrease DA activity in the kidney by inhibiting DA synthesis via carbidopa administration. We want to compare findings in normal volunteers and in patients with postural tachycardia syndrome (POTS). We will test the null hypothesis (Ho) that the effects of oral carbidopa administration on urinary sodium excretion will not differ between patients with POTS and healthy volunteers.

Conditions

Postural Tachycardia Syndrome; Orthostatic Intolerance

Keywords

Dopamine; Natriuresis; Catecholamines

Outcome Measures

Primary Outcomes (1)

• 24 Hour Urinary Sodium Excretion During Treatment Normalized to Creatinine

  Urine was collected for 24hr during treatment. Urinary volume was measured and the urine was analyzed for sodium and creatinine concentrations. Total amounts of sodium and creatinine excreted over the 24 hr were calculated and results expressed as ratio of sodium:creatinine.

  Immediately before the 1st dose of placebo or carbidopa to immediately before the 5th dose (approximately 24 hours)

Secondary Outcomes (7)

• Systolic Blood Pressure Measured at 8 Hours After the Last Dose of Placebo or Carbidopa

  8 hours after the last dose of placebo or carbidopa

• Plasma Catecholamines (Norepinephrine) After the Last Dose of Placebo or Carbidopa

  8 hours after the last dose of placebo or carbidopa

• Plasma Catecholamines (DOPA) After the Last Dose of Placebo or Carbidopa

  8 hours after the last dose of placebo or carbidopa

• 24 Hour Urinary Catecholamine (DOPA) Excretion During Treatment Normalized to Creatinine

  Immediately before the 1st dose of Placebo or Carbidopa and ending immediately before the last dose (approximately 24 hours)

• 24 Hour Urinary Catecholamine (Dopamine) Excretion During Treatment Normalized to Creatinine

  Immediately before the 1st dose of Placebo or Carbidopa and ending immediately before the last dose (approximately 24 hours)

Study Arms (2)

Carbidopa then Placebo

EXPERIMENTAL

Carbidopa 200 mg every 6 hours orally for 5 doses followed by Placebo every 6 hours for 5 doses

Drug: Carbidopa; Drug: Placebo

Placebo then Carbidopa

EXPERIMENTAL

Placebo matching carbidopa given every 6 hours orally for 5 doses followed by Carbidopa

Drug: Carbidopa; Drug: Placebo

Interventions

Carbidopa DRUG

200 mg every 6 hours for 5 doses given orally

Carbidopa then Placebo; Placebo then Carbidopa

Placebo DRUG

every 6 hours for 5 doses, given orally, and matching Carbidopa

Carbidopa then Placebo; Placebo then Carbidopa

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Patients diagnosed with POTS by the Vanderbilt Autonomic Dysfunction Center based on the following stringent criteria: 1) history of daily orthostatic symptoms for at least 6 months; 2) increase in heart rate (HR) of at least 30 bpm with standing or a standing HR of at least 120 bpm; 3) absence of orthostatic hypotension (defined as a fall in blood pressure (BP)\>20/10 mm Hg); and 4) absence of conditions, such as dehydration, substantial weight loss, or systemic illnesses, that could provoke orthostatic intolerance
• Upright plasma NE at least 600 pg/mL in patients
• Non-smoking
• Free of medications with the potential to influence BP
• Able and willing to provide informed consent -

You may not qualify if:

• Overt cause for postural tachycardia (such as acute dehydration)
• 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

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (6)

• Carey RM. Theodore Cooper Lecture: Renal dopamine system: paracrine regulator of sodium homeostasis and blood pressure. Hypertension. 2001 Sep;38(3):297-302. doi: 10.1161/hy0901.096422.

  PMID: 11566894 BACKGROUND

• Goldstein DS, Stull R, Eisenhofer G, Gill JR Jr. Urinary excretion of dihydroxyphenylalanine and dopamine during alterations of dietary salt intake in humans. Clin Sci (Lond). 1989 May;76(5):517-22. doi: 10.1042/cs0760517.

  PMID: 2498027 BACKGROUND

• Jose PA, Eisner GM, Felder RA. Renal dopamine and sodium homeostasis. Curr Hypertens Rep. 2000 Apr;2(2):174-83. doi: 10.1007/s11906-000-0079-y.

  PMID: 10981146 BACKGROUND

• Kuchel O, Buu NT, Unger T. Dopamine-sodium relationship: is dopamine a part of the endogenous natriuretic system? Contrib Nephrol. 1978;13:27-36. doi: 10.1159/000402132.

  PMID: 710137 BACKGROUND

• Stokes GS, Monaghan JC, Pillai DN. Effects of carbidopa and of intravenous saline infusion into normal and hypertensive subjects on urinary free and conjugated dopamine. J Hypertens. 1997 Jul;15(7):761-8. doi: 10.1097/00004872-199715070-00008.

  PMID: 9222944 BACKGROUND

• Jacob G, Robertson D, Mosqueda-Garcia R, Ertl AC, Robertson RM, Biaggioni I. Hypovolemia in syncope and orthostatic intolerance role of the renin-angiotensin system. Am J Med. 1997 Aug;103(2):128-33. doi: 10.1016/s0002-9343(97)00133-2.

  PMID: 9274896 BACKGROUND

MeSH Terms

Conditions

Postural Orthostatic Tachycardia Syndrome; Orthostatic Intolerance

Interventions

Carbidopa

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Methyldopa; Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Hydrazines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Alfredo Gamboa, MD
• Organization: Vanderbilt University Medical Center

alfredo.gamboa@vumc.org

615-875-1003

Study Officials

• Alfredo J Gamboa, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Associate Professor of Medicine

Study Record Dates

• First Submitted: May 27, 2008
• First Posted: May 29, 2008
• Study Start: May 1, 2008
• Primary Completion: July 1, 2020
• Study Completion: December 1, 2021
• Last Updated: January 24, 2022
• Results First Posted: September 20, 2021

Record last verified: 2022-01

Locations

US (1)