V2 Receptor Effects on Fluid Regulation and Performance

This study has been completed.
Sponsor:
Collaborator:
Georgetown University
Information provided by (Responsible Party):
Oakland University
ClinicalTrials.gov Identifier:
NCT02084797
First received: March 10, 2014
Last updated: March 11, 2014
Last verified: March 2014
  Purpose

This primary aim of this study was to critically assess whether or not sweat water content and sodium concentration were acutely regulated by dynamic changes in antidiuretic hormone (arginine vasopressin or AVP) acting on the Vasopressin 2 receptor (V2R) during exercise. Secondary aims were to evaluate running performance and core temperature to further characterize the role of AVP in the coordinated balance of fluid and temperature homeostasis during exercise. The primary hypothesis was that activation of the V2R in sweat glands would result in water reabsorption and fluid conservation during endurance exercise.


Condition Intervention
Determine if Sweat [Na+] is Regulated by the V2R
Drug: V2R (Vasopressin 2 receptor)

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: Revisiting the Human Sweat Gland - Does Arginine Vasopressin Modulate Sweat Sodium Concentration Via the V2 Receptor?

Resource links provided by NLM:


Further study details as provided by Oakland University:

Primary Outcome Measures:
  • Sweat sodium concentration [ Time Frame: 4 study trials (4 weeks) ] [ Designated as safety issue: No ]
    Changes in sweat sodium concentration will parallel changes in urine sodium concentration with use of the V2R antagonist, agonist and placebo if the primary hypothesis is true (sweat sodium is regulated by the V2R, similar to how urine sodium is regulated by principle cells located within in the kidney collecting duct)


Secondary Outcome Measures:
  • Urine Sodium Concentration [ Time Frame: 4 study trials (4 weeks) ] [ Designated as safety issue: No ]
    Changes in urine sodium concentration after use of the V2R antagonist, agonist and placebo interventions will verify whether or not pharmacologic activation or inhibition was successfully induced.

  • Blood sodium concentration [ Time Frame: 4 study trials (4 weeks) ] [ Designated as safety issue: No ]
    Measurement of blood sodium concentration will determine if normonatremia (blood sodium concentrations within the normal physiological range of 135-145mmol/L) were maintained throughout the trial with appropriate fluid intake during the V2R antagonist, agonist and placebo intervention trials.

  • Saliva sodium concentration [ Time Frame: 4 trials (4 weeks) ] [ Designated as safety issue: No ]
    Measurement of salivary sodium concentration will allow us to determine if the V2R antagonist, agonist and placebo interventions activate aquaporin-5 (AQP5) water channels that are also located in sweat glands. If the V2R acts on the sweat glands through AQP5, there should be parallel changes in sweat, urine and saliva sodium concentrations with each pharmaceutical intervention.


Other Outcome Measures:
  • Body weight [ Time Frame: 4 trials (4 weeks) ] [ Designated as safety issue: No ]
    Changes in body weight during the V2R antagonist, agonist and placebo conditions will provide researchers with an additional measure of overall fluid balance (fluid in versus fluid out) as well as an estimate of overall sweat water losses.

  • Core Temperature [ Time Frame: 4 trials (4 weeks) ] [ Designated as safety issue: No ]
    Measurement of core temperature using an ingestible CorTemp sensor during the V2R antagonist, agonist and placebo trials will allow researchers to assess if fluid homeostasis and thermoregulation were intertwined in response to each pharmacological intervention.

  • Thirst Rating [ Time Frame: 4 trials (4 weeks) ] [ Designated as safety issue: No ]
    To determine if fluid intake behaviors were appropriately regulated in response to the V2R antagonist, agonist and placebo conditions during exercise.

  • Sodium palatability ratings [ Time Frame: 4 weeks (4 trials) ] [ Designated as safety issue: No ]
    To determine if sodium preference ratings were appropriately regulated in response to the V2R antagonist, agonist and placebo conditions during exercise.

  • Performance [ Time Frame: 4 trials (4 weeks) ] [ Designated as safety issue: No ]
    To determine if exercise performance, as determined by overall exercise time, was affected in response to the V2R antagonist, agonist and placebo conditions.

  • Fluid intake [ Time Frame: 4 weeks (4 trials) ] [ Designated as safety issue: No ]
    To determine if fluid intake behaviors were appropriately regulated in response to the V2R antagonist, agonist and placebo conditions during exercise.


Enrollment: 10
Study Start Date: June 2011
Study Completion Date: October 2012
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
This study was a double-blind randomized controlled trial in which all ten subjects participated in three trials under three separate pharmacological interventions: V2R antagonist, agonist and placebo conditions. A standardized exercise protocol was performed in the laboratory, separated by one week. Each subject served as his or her own control and the key which identified which intervention was utilized in the exact order (all tablets customized to appear identical) was unlocked only after data collection was completed. Therefore, all ten subjects participated in a total of thirty intervention exercise trials after the initial treadmill familiarization trial was completed.
Drug: V2R (Vasopressin 2 receptor)
All ten subjects were used as their own controls in this double-blind, randomized controlled trial assessing the effect of the V2R on sweat sodium concentration via use of a V2R blocker (antagonist), stimulator (agonist), against a placebo (drug naive state).
Other Names:
  • V2R antagonist: tolvaptan (30mg tablet)
  • V2R agonist: desmopressin (0.2mg tablet)

Detailed Description:

Ten healthy habitual runners (> 50km running per week) between 18-60 years of age participated in this double blind randomized control trial. Each subject presented to the exercise lab on four separate occasions. Trial 1 was a familiarization trial to determine each subject's maximal aerobic capacity and peak treadmill running speak (VO2 Peak test). Trials 2, 3 and 4 utilized the same exact protocol, differing only in pharmacological intervention. In a randomized, double-blind order (both participant and investigator blinded to the intervention), either a placebo pill, the V2 receptor antagonist tolvaptan (Samsca™, 30mg tablet), or the V2 receptor agonist desmopressin (DDAVP™, 0.2mg tablet) was ingested along with the CorTemp™ Core Temperature Sensor two hours before commencement of the Exercise Trial with 240mL of bottled water. The exercise protocol consisted of 60 minutes of treadmill running at 60% of peak speed (steady-state) followed by a performance test (the VO2 Peak test). Blood, saliva and urine, were collected before the exercise trial (baseline) and again after both the steady-state run and performance runs. Sweat was obtained from sweat patches after both the steady-state and performance runs. Core temperature, fluid intake, performance time, body weight, thirst and sodium palatability ratings were also assessed. Free access to water was allowed during the trial and all urine produced during the trial was measured and collected. The main outcome measure was sweat sodium concentration.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy (no acute or chronic medical conditions or regular prescription medication use), habitual (>50km/week)
  • Distance runners between the ages of 18-60 years.

Exclusion Criteria:

  • Individuals with chronic medical problems which require regular prescription medication
  • Runners with pre-existing kidney problems
  • Unable to sense thirst
  • Difficulty swallowing
  • Gastrointestinal disorders
  • History of fainting associated with blood draw.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT02084797

Locations
United States, Michigan
Oakland University
Rochester, Michigan, United States, 48309
Sponsors and Collaborators
Oakland University
Georgetown University
Investigators
Principal Investigator: Tamara D Hew-Butler, PhD Oakland University
Study Director: Joseph G Verbalis, MD Georgetown University
  More Information

No publications provided

Responsible Party: Oakland University
ClinicalTrials.gov Identifier: NCT02084797     History of Changes
Other Study ID Numbers: RAM#4713
Study First Received: March 10, 2014
Last Updated: March 11, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Oakland University:
arginine vasopressin
sweat sodium
V2 antagonist
running

Additional relevant MeSH terms:
Diabetes Insipidus
Kidney Diseases
Urologic Diseases
Pituitary Diseases
Endocrine System Diseases
Arginine Vasopressin
Vasopressins
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Vasoconstrictor Agents
Cardiovascular Agents
Antidiuretic Agents
Natriuretic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 31, 2014