Fractional Urate Excretion in Nonedematous Hyponatremia

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2012 by Winthrop University Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Winthrop University Hospital
ClinicalTrials.gov Identifier:
NCT01425125
First received: August 25, 2011
Last updated: July 30, 2012
Last verified: July 2012
  Purpose

Hyponatremia, defined as a serum sodium < 135 mmol/l, in patients without edema has undergone significant changes where it is now evident that even mild hyponatremia should be treated because of its association with symptoms, especially a fourfold increase in falls over the age of 65 years. There is an unresolved controversy over the relative prevalence of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and cerebral/renal salt wasting (C/RSW). Resolution of this diagnostic dilemma becomes urgent because of divergent therapeutic goals, to water-restrict in SIADH or to give salt and water supplementation in C/RSW. The dilemma is compounded by recent reports of C/RSW occurring in patients without cerebral disease, thus adding further confusion in defining the relative prevalence of both syndromes. Because of overlapping laboratory and clinical findings in both syndromes, only differences in the state of extracellular volume differentiates one syndrome from the other, being high normal to increased in SIADH and decreased in C/RSW. The investigators have used fractional excretion (FE) of urate to categorize patients with hyponatremia. The increased FEurate that is observed in hyponatremic patients with SIADH and C/RSW can be used to differentiate both syndromes by correcting the hyponatremia and determining whether FEurate normalizes as in SIADH or remains increased in C/RSW. The present studies have been designed to determine total body water by deuterium and extracellular water by sodium bromide in patients with nonedematous hyponatremia with normal and increased FEurate to differentiate more conclusively whether the patient has normal or decreased water volumes. The investigators will also correct serum sodium rapidly with judicious administration of hypertonic saline over approximately three days and determine whether FEurate normalizes as in SIADH or remains increased as in C/RSW. In another group of patients, The investigators have data to suggest that those with normal sodium and increased FEurate is consistent with C/RSW. The investigators intend to do the same water volume studies to determine whether an increased FEurate with normonatremia would have decreased total and extracellular water that these patients have C/RSW without the need to correct a prior hyponatremia.


Condition Intervention
Cerebral Hyponatremia
SIADH
Cerebral Salt-wasting Syndrome
Reset Hypothalamic Osmostat
Drug: Tolvaptan in euvolemic hyponatremia

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Study of Nonedematous Hyponatremia and the Utility of Fractional Urate Excretion in Hyponatremia and Suspected Renal Salt Wasting Without Hyponatremia-

Resource links provided by NLM:


Further study details as provided by Winthrop University Hospital:

Primary Outcome Measures:
  • Etiologic categorization of nonedematous hyponatremia [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    We will attempt to categorize the etiology of nonedematous hyponatremia by the following parameters in decreasing order of importance, total and extracellular water determinations, fractional urate excretion, plasma renin and aldosterone levels, urinary sodium concentration and urine osmolality. We will also determine total and extracellular water in a group suspected of having renal salt wasting by virtue of having increased fractional urate excretion and normal serum sodium concentrations.


Estimated Enrollment: 20
Study Start Date: November 2011
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tolvaptan in euvolemic hyponatremia
This arm will test the effectiveness of tolvaptan in treating the hyponatremia of patients with euvolemic hyponatremia.
Drug: Tolvaptan in euvolemic hyponatremia
This arm will test the effectiveness of tolvaptan in treating the hyponatremia of patients with euvolemic hyponatremia.
Other Name: oral tolvaptan (Samsca

Detailed Description:

The investigators have demonstrated that a normal FEurate in a nonedematous hyponatremic patient is highly consistent with the diagnosis of reset osmostat (RO). Since as much as 36% of patients with SIADH have RO, the investigators will evaluate these patients by either noting dilute urines in spontaneously excreted urines or after a modified water-loading test. The investigators have found that a normal FEurate in a nonedematous hyponatremic patient is highly consistent with RO.

The investigators intend to treat euvolemic patients with hyponatremia with tolvaptan, the V2 ADH receptor blocker, to determine the effectiveness of this form of therapy in a group of patients in whom correction of hyponatremia has been difficult to achieve by usual methods.

Nonedematous hyponatremic patients with serum sodium < 135 mmol/l will be recruited from Winthrop-University Hospital and from our outpatient practice.

It is anticipated that the present studies will provide valuable information on the relative prevalence of SIADH and C/RSW in patients with nonedematous hyponatremia. One possible drawback to these studies is our inability to determine total and extracellular water volumes in patient who are admitted to the neuro/neurosurgical ICU where the acute illnesses require parenteral therapy that will create a nonsteady state situation where total and extracellular water volumes cannot be accurately determined. This is an important possible omission because volume studies in this population of studies have indicated more that two thirds of patients having decreased volumes that were consistent with C/RSW, yet the medical literature states that C/RSW is rare. Studies in hyponatremics elsewhere in the hospital should shed important light on the methods to differentiate SIADH from C/RSW, data which can assist us in differentiating both syndromes in the neuro/neurosurgical ICU, where the investigators intend to perform FEurates.

It is anticipated that volume studies in patients with Alzheimer's disease with normal serum sodium and increased FEurate will demonstrated decreased volumes and confirm our earlier observations that many of these patients are renal salt wasters. It would be interesting to test whether volume repletion with saline will improve them mentally and physically.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

- Nonedematous hyponatremia with normal renal, adrenal and thyroid function. -Non-hyponatremia with increased fractional excretion of urate.

Exclusion Criteria:

  • Subjects < 18 years of age
  • Pregnancy
  • Serum creatinine > 1.4 mg/dl
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01425125

Contacts
Contact: John K Maesaka, MD 516-663-2169 jmaesaka@winthrop.org
Contact: Louis J Imbriano, MD 516-663-2169 limbriano@wnthrop.org

Locations
United States, New York
Winthrop-University Hospital Recruiting
Mineola, New York, United States, 11501
Contact: John K Maesaka, MD    516-663-2169    jmaesaka@winthrop.org   
Contact: Louis J Imbriano, MD    516-663-2169    limbriano@winthrop.org   
Sponsors and Collaborators
Winthrop University Hospital
Investigators
Principal Investigator: John K Maesaka, MD Winthrop University Hospital
Study Director: Louis J Imbriano, MD Winthrop University Hospital
  More Information

No publications provided

Responsible Party: Winthrop University Hospital
ClinicalTrials.gov Identifier: NCT01425125     History of Changes
Other Study ID Numbers: 10029, 10029
Study First Received: August 25, 2011
Last Updated: July 30, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Winthrop University Hospital:
nonedematous hyponatremia
fractional urate excretion

Additional relevant MeSH terms:
Hyponatremia
Wasting Syndrome
Metabolic Diseases
Nutrition Disorders
Water-Electrolyte Imbalance

ClinicalTrials.gov processed this record on October 23, 2014