Cerebral HyponatremiaNCT01425125
Fractional Urate Excretion in Nonedematous Hyponatremia
A study testing Tolvaptan in euvolemic hyponatremia in people with Cerebral Hyponatremia and SIADH, run by NYU Langone Health at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cerebral Hyponatremia, SIADH, Cerebral Salt-wasting Syndrome
- What is being tested?
- Tolvaptan in euvolemic hyponatremia
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2011to Dec 2014
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Nonedematous hyponatremia with normal renal, adrenal and thyroid function. -Non-hyponatremia with increased fractional excretion of urate.
Who cannot join
- Subjects < 18 years of age
- Pregnancy
- Serum creatinine > 1.4 mg/dl
Trial locations and contacts
1 site in 1 country.
United States1 site
Winthrop-University Hospital
Mineola, New York, 11501
About this study
Official title: Study of Nonedematous Hyponatremia and the Utility of Fractional Urate Excretion in Hyponatremia and Suspected Renal Salt Wasting Without Hyponatremia-
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.
Read the 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.
- Being tested
- Tolvaptan in euvolemic hyponatremia
- Keywords
- nonedematous hyponatremia, fractional urate excretion
- Medical subject headings
- Inappropriate ADH Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tolvaptan in euvolemic hyponatremiaDrug
Also called oral tolvaptan (Samsca
This arm will test the effectiveness of tolvaptan in treating the hyponatremia of patients with euvolemic hyponatremia.
| Study group | Role | What they receive |
|---|---|---|
| Tolvaptan in euvolemic hyponatremia | Experimental | This arm will test the effectiveness of tolvaptan in treating the hyponatremia of patients with euvolemic hyponatremia. Receives: Drug: Tolvaptan in euvolemic hyponatremia |
What is being measured
The primary outcome is the main question the study is designed to answer.
Etiologic categorization of nonedematous hyponatremia
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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2011 (estimated)
- Study startNov 2011
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cerebral HyponatremiaStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- John K Maesaka, MD, Principal investigator, Winthrop University HospitalLouis J Imbriano, MD, Study director, Winthrop University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01425125
- Sponsor's protocol ID
- 10029
- Other IDs
- 10029
- Status last verified
- Feb 2019
- First submitted
- 25 Aug 2011
- Last updated
- 6 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Nonedematous Hyponatremia and the Utility of Fractional Urate Excretion in Hyponatremia and Suspected Renal Salt Wasting Without Hyponatremia-
- ClinicalTrials.gov ID
- NCT01425125
- Acronym / sponsor ID
- 10029
- Keywords
- nonedematous hyponatremia, fractional urate excretion
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Study start
- Nov 2011
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 29 Aug 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tolvaptan in euvolemic hyponatremia | Experimental | Drug: Tolvaptan in euvolemic hyponatremiaThis arm will test the effectiveness of tolvaptan in treating the hyponatremia of patients with euvolemic hyponatremia. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Nonedematous hyponatremia with normal renal, adrenal and thyroid function. -Non-hyponatremia with increased fractional excretion of urate.
Key exclusion criteria (3 listed)
- Subjects < 18 years of age
- Pregnancy
- Serum creatinine > 1.4 mg/dl
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tolvaptan in euvolemic hyponatremiaAlso: oral tolvaptan (SamscaThis arm will test the effectiveness of tolvaptan in treating the hyponatremia of patients with euvolemic hyponatremia. | Drug | Tolvaptan in euvolemic hyponatremia |
Primary outcome
Etiologic categorization of nonedematous hyponatremia
Time frame: 2 years
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.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2019.
Related trials for Cerebral Hyponatremia
Enrolling by invitationObservational study
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Hyponatremia Symptomatic, Osmotic Demyelination Syndrome
Active, not recruitingObservational study
Samsca Post-marketing General Drug Use-results Survey in Patients With Hyponatremia in SIADH
Antidiuretic Hormone, Inappropriate Secretion
Recruiting
Urea for Treatment of Hyponatremia in Patients With SIAD Unresponsive to Fluid Restriction
SIAD - Syndrome of Inappropriate Antidiuresis
Recruiting
Protein Supplementation in Hyponatremia Due to the Syndrome of Inappropriate Antidiuresis
Hyponatremia, Syndrome of Inappropriate Antidiuresis
Active, not recruiting
Urea Therapy for Hyponatremia in Subarachnoid Hemorrhage
Hyponatremia, Subarachnoid Hemorrhage
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John K Maesaka, MD principal investigator
Winthrop University Hospital
Louis J Imbriano, MD study director
Winthrop University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Tolvaptan in euvolemic hyponatremia in people with Cerebral Hyponatremia and SIADH, run by NYU Langone Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 6 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Etiologic categorization of nonedematous hyponatremia (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2019.