- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04588207
Urea for Chronic Hyponatremia
Urea for Chronic Hyponatremia: A Pilot Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Hyponatremia is the most common electrolyte disorder encountered clinically. While acute and/or severe hyponatremia is commonly associated with significant symptoms, milder and more chronic forms of hyponatremia remain clinically inconspicuous as the brain effectively adapts to the low extracellular osmolality. However, recent evidence suggests that even mild hyponatremia is associated with subtle neurocognitive deficits, gait disturbances, falls, fractures, and osteoporosis, as well as increased mortality. Current therapeutic interventions for hyponatremia, including fluid restriction and loop diuretics lack clinical trial data to support their efficacy and are commonly associated with poor adherence. The discovery of vasopressin antagonists (vaptans) provided a new drug class targeting the most common mechanism of hyponatremia, i.e., elevated vasopressin. Despite the demonstrated efficacy of vaptans in clinical trials, their use has been limited by high cost as well as safety concerns related to risk of liver injury and the potential for rapid correction of hyponatremia. Thus, despite the significant morbidity and mortality associated with chronic non-severe hyponatremia, there is a paucity of definitively effective, safe, well-tolerated, and reasonably priced treatments.
Small European case series have suggested that oral urea is safe and effective for the treatment of hyponatremia. However, urea has not been available for the treatment of hyponatremia in the United States until very recently. This research group recently published the first and only study describing the effectiveness and safety of a new American formulation of oral urea among hospitalized patients with hyponatremia. However, the latter was a retrospective study limited to hospitalized patients. Data from large clinical trials on the efficacy of urea for the prevention of patient-centered outcomes in those with chronic hyponatremia are lacking. The current proposal is a pilot study that seeks to establish the feasibility of recruiting ambulatory patients with chronic hyponatremia into a study of urea, determine the acceptability of urea to patients, and explore the effect of this agent on plasma sodium level (PNa), neurocognitive function, and postural stability. The investigators will recruit 30 ambulatory patients with chronic non-severe hyponatremia and randomize them to oral urea or no drug treatment for a period of 42 days. Following this initial phase, all participants will have a 10-day washout period, followed by a 42-day period in which participants initially randomized to no drug therapy will receive urea and those initially treated with urea will receive no drug therapy. The investigators will collect data regarding the ease of recruitment, participant adherence to urea, and adverse events related to its use. The investigators will monitor participants' PNa, neurocognitive function, and postural stability over the course of the study. The feasibility, acceptability, and proof of concept/efficacy data from this pilot study will confirm the investigator's capacity to conduct, and will inform the design of a large clinical trial that will assess the efficacy of urea for the prevention of serious clinical outcomes of chronic non-severe hyponatremia.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Rachel Cohen, BA, RN
- Phone Number: 412-647-1376
- Email: rkc16@pitt.edu
Study Locations
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, United States, 15261
- University of Pittsburgh Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age ≥18 years
- Attended ≥1 visit at a University of Pittsburgh Medical Center (UPMC) outpatient clinic within the prior 12 months
- Chronic hyponatremia with a history of ≥ 2 sequential plasma sodium concentration (PNa) between 125 mmol/L and 132 mmol/L performed ≥ 14 days apart within the last 12 months with most recent PNa ≤ 132 mmol/L prior to screening
- Patients are ambulatory without the need for any assist device (e.g., cane, walker)
- Mini-mental state examination (MMSE) score ≥ 25
Diagnosis of SIADH established by the Bartter and Schwartz criteria as follows:
- Hyponatremia with a PNa between 125 mmol/L and 132 mmol/L
- Plasma osmolality < 275 mOsm/kg
- Clinical euvolemia
- Urine osmolality > 100 mosm/kg
- Urine Na ≥ 20 mmol/L
- Intact adrenal function (i.e., morning plasma cortisol value ≥15 μg/dL, or negative corticotropin stimulation test)
- Normal thyroid stimulating hormone (TSH) level (i.e., TSH between 0.3 to 5 μIU/mL)
- eGFR >= 45 ml/min/1.73 m2)
Exclusion Criteria:
- Cirrhosis and/or end-stage liver disease
- Heart failure on diuretics and/or with recorded left ventricular ejection fraction <40 percent
- Chronic kidney disease with most recent estimated glomerular filtration rate <45 ml/min/1.73m2
- Adrenal insufficiency
- Untreated hypothyroidism
- Urinary tract obstruction within the prior 2 months
- Uncontrolled hyperglycemia (most recent random plasma glucose ≥ 200 mg/dL)
- Ongoing drug treatment for hyponatremia with vaptans or combination of loop diuretics and salt tablets.
- Active malignancy
- Active infection
- Neurological disorders with impairment of ambulation or cognition
- End-stage lung disease with marked impairment in ambulatory capacity
- Chronic pain with impairment of ambulation or cognition
- Chronic nausea
- Hypersensitivity to urea
- Women who are pregnant, breast feeding, or of childbearing potential who are not using contraception
- Patient is unable to consent for himself/herself
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: On Urea, Then Off Urea
Participants assigned to this group will receive oral urea for 42 days (period 1), followed by a 10-day washout period, and then will be off urea for 42 days (period 2).
|
Groups "On Urea, Then Off Urea" and "Off Urea, Then On Urea" will receive urea during period 1 and period 2 of the study, respectively.
The investigators will use the new American formulation of oral urea (i.e., Ure-Na™), which is packaged as a powder and mixed with 4 ounces. of water for oral consumption.
Urea will be started at a dose of 15 grams of urea per mouth once daily.
Dose titration will be based on the absolute increase in PNa on days 7 and 14.
The urea dosing scheme will involve increasing from the starting dose of 15 grams/day to 30 grams/day (in 2 divided doses) based on the change in and absolute value of PNa, and subsequently, from 30 grams/day to 60 grams/day (in 2 divided doses) when indicated.
The maximal dose of urea administered will be 60 g/day.
Other Names:
|
Experimental: Off Urea, Then On Urea
Participants assigned to this group will be off urea during for 42 days (period 1), followed by a 10-day washout period, and then on urea for 42 days (period 2)
|
Groups "On Urea, Then Off Urea" and "Off Urea, Then On Urea" will receive urea during period 1 and period 2 of the study, respectively.
The investigators will use the new American formulation of oral urea (i.e., Ure-Na™), which is packaged as a powder and mixed with 4 ounces. of water for oral consumption.
Urea will be started at a dose of 15 grams of urea per mouth once daily.
Dose titration will be based on the absolute increase in PNa on days 7 and 14.
The urea dosing scheme will involve increasing from the starting dose of 15 grams/day to 30 grams/day (in 2 divided doses) based on the change in and absolute value of PNa, and subsequently, from 30 grams/day to 60 grams/day (in 2 divided doses) when indicated.
The maximal dose of urea administered will be 60 g/day.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number and Proportion of Participants who Met Inclusion/Exclusion Criteria and were Enrolled in the Study
Time Frame: 13.5 months
|
Number and proportion of participants who met inclusion/exclusion criteria and were enrolled in the study.
To be assessed by analysis of enrollment data.
|
13.5 months
|
Number and Proportion of Participants Enrolled who Completed the Study
Time Frame: 13.5 months
|
Number and proportion of participants enrolled who completed the study.
To be assessed by analysis of enrollment and completion data.
|
13.5 months
|
Monthly Enrollment Rate
Time Frame: 13.5 months
|
Number of participants enrolled in the study every month.
To be assessed by analysis of enrollment data
|
13.5 months
|
Number of Prescribed Urea Doses Taken by Participants
Time Frame: Baseline to day 42 while taking urea
|
Number of prescribed urea doses taken by participants.
To be assessed by records in study diary and number of returned medication doses.
|
Baseline to day 42 while taking urea
|
Reasons for Non-Adherence to Urea Therapy
Time Frame: Baseline to day 42 while taking urea
|
Reasons for non-adherence to urea therapy.
To be assessed by medication acceptability and medication side effect questionnaires
|
Baseline to day 42 while taking urea
|
Change in Plasma Sodium Concentration
Time Frame: Baseline to day 42
|
Change in plasma sodium concentration from baseline to day 42.
Based on plasma sodium assessments on days 0 and 42.
|
Baseline to day 42
|
Change in Percentage Accuracy Action Boundary Selection
Time Frame: Baseline to day 42
|
Change in percentage accuracy action boundary selection from baseline to day 42.
This will be measured by the Perception-Action Coupling Task (PACT) which is an affordance-based assessment conducted on an iPad, which uses matched pairs of 'virtual' balls and 'virtual' holes to assess patients' ability to accurately assess their action boundaries.
|
Baseline to day 42
|
Change in Overall Score of Sensorimotor Ability Battery
Time Frame: Baseline to day 42
|
Change in overall score of sensorimotor ability battery from baseline to day 42.
This will be measured by the Senaptec Sensory Station™ test battery which examines separate sensorimotor elements including; multiple object tracking, reaction time, perception span, go/no go, depth perception and dynamic visual acuity.
The overall score ranges from 0 to 100 where a higher score indicates a better outcome.
|
Baseline to day 42
|
Change in the Sample Entropy of the Center of Pressure Data from the Force Plate
Time Frame: Baseline to day 42
|
Change in the sample entropy of the center of pressure data from the force plate.
The complexity and control of the static representation of postural stability in quiet upright stance will be determined employing non-linear analysis (sample entropy).
|
Baseline to day 42
|
Change in Percentage Angular Deviation of Vestibular Control System using Dynamic Representation of Upright Stance
Time Frame: Baseline to day 42
|
Change in percentage angular deviation of vestibular control system using dynamic representation of upright stance from baseline to day 42.
This will be assessed using the NeuroCom™ Sensory Organization.
This test enables both the examination of postural control and stability in response to a direct perturbation of the vestibular control system underlying the maintenance of upright posture, giving insight into the relative contributions and/or any deficits in the vestibular system involved in maintaining upright stance in dynamic situations.
|
Baseline to day 42
|
Change in Percentage Angular Deviation of Somatosensory Control System using Dynamic Representation of Upright Stance
Time Frame: Baseline to day 42
|
Change in percentage angular deviation of somatosensory control system using dynamic representation of upright stance from baseline to day 42.
This will be assessed using the NeuroCom™ Sensory Organization.
This test enables both the examination of postural control and stability in response to a direct perturbation of the somatosensory control system underlying the maintenance of upright posture, giving insight into the relative contributions and/or any deficits in the somatosensory system involved in maintaining upright stance in dynamic situations.
|
Baseline to day 42
|
Change in Percentage Angular Deviation of Visual Control System using Dynamic Representation of Upright Stance
Time Frame: Baseline to 42 days
|
Change in percentage angular deviation of visual control system using dynamic representation of upright stance from baseline to day 42.
This will be assessed using the NeuroCom™ Sensory Organization.
This test enables both the examination of postural control and stability in response to a direct perturbation of the visual control system underlying the maintenance of upright posture, giving insight into the relative contributions and/or any deficits in the visual system involved in maintaining upright stance in dynamic situations.
|
Baseline to 42 days
|
Change in Percentage Weight Symmetry using Dynamic Representation of Upright Stance
Time Frame: Baseline to day 42
|
Change in percentage weight symmetry using dynamic representation of upright stance from baseline to day 42.
This will be assessed using the Motor Control Test (MCT).
MCT assesses the ability to quickly recover from an unexpected external translation.
|
Baseline to day 42
|
Change in Movement Latency of Posture Control and Stability using Dynamic Representation of Upright Stance
Time Frame: Baseline to day 42
|
Change in movement latency of posture control and stability using dynamic representation of upright stance from baseline to day 42.
This will be assessed using the Motor Control Test (MCT).
MCT assesses the ability to quickly recover from an unexpected external translation.
|
Baseline to day 42
|
Change in Amplitude Scaling of Posture Control and Stability using Dynamic Representation of Upright Stance
Time Frame: Baseline to day 42
|
Change in amplitude scaling of posture control and stability using dynamic representation of upright stance from baseline to day 42.
This will be assessed using the Motor Control Test (MCT).
MCT assesses the ability to quickly recover from an unexpected external translation.
|
Baseline to day 42
|
Number and Proportion of Participants Enrolled in the Study with Adverse Events Related to the Use of Urea
Time Frame: Baseline to day 42 while taking urea
|
Number and proportion of participants enrolled in the study with adverse events related to the use of urea from baseline to day 42.
To be assessed by medication side effect questionnaire.
|
Baseline to day 42 while taking urea
|
Adverse Events Related to Urea
Time Frame: Baseline to day 42 while taking urea
|
To be assessed by medication side effect questionnaire.
A tabulation of counts of participants experiencing specific known side effects of urea as well as their intensity (mild, moderate or severe) will be performed.
|
Baseline to day 42 while taking urea
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Patients Screened
Time Frame: 13.5 months
|
Number of patients screened.
To be assessed by analysis of screening data.
|
13.5 months
|
Number and Proportion of Patients Screened who Met Inclusion/Exclusion Criteria for the Study
Time Frame: 13.5 months
|
Number and proportion of patients screened who met inclusion/exclusion criteria for the study. To be assessed by analysis of screening and enrollment data. |
13.5 months
|
Number and Proportion of Participants who Took More than 80 Percent of Prescribed Urea Doses
Time Frame: Baseline to day 42 while taking urea
|
Number and proportion of participants who took more than 80 percent of prescribed urea doses.
To be assessed by analysis of study diary and number of returned medication doses.
|
Baseline to day 42 while taking urea
|
Number and Proportion of Participants who Thought the Medication was Acceptable
Time Frame: Baseline to day 42 while taking urea
|
Number and proportion of participants who thought the medication was acceptable.
Based on ratings for acceptability in the medication acceptability questionnaire.
|
Baseline to day 42 while taking urea
|
Average Ratings for Medication Acceptability
Time Frame: Baseline to day 42 while taking urea
|
Average ratings using a 5-point Likert scale 19-item medication acceptability questionnaire. in which responders specify their level of agreement to a statement in five points: (1) Strongly disagree; (2) Disagree; (3) Neutral; (4) Agree; (5) Strongly agree; or (1) Very Unhappy; (2) Unhappy; (3) Neutral; (4) Happy; (5) Very Happy.
|
Baseline to day 42 while taking urea
|
Change in SF-12 (Health Survey) Mental Component Summary (MCS)
Time Frame: Baseline to day 42
|
Change in SF-12 (Health Survey) Mental Component Summary (MCS) from baseline to day 42.
Based on SF-12 MCS assessments on days 0 and 42.
This is computed using the scores of 12 questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
|
Baseline to day 42
|
Change in SF-12 (Health Survey) Physical Component Summary (PCS)
Time Frame: Baseline to day 42
|
Change in SF-12 (Health Survey) Physical Component Summary (PCS) from baseline to day 42.
Based on SF-12 PCS assessments on days 0 and 42.
This is computed using the scores of 12 questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
|
Baseline to day 42
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Helbert Rondon Berrios, MD. MS, University of Pittsburgh
Publications and helpful links
General Publications
- Soupart A, Coffernils M, Couturier B, Gankam-Kengne F, Decaux G. Efficacy and tolerance of urea compared with vaptans for long-term treatment of patients with SIADH. Clin J Am Soc Nephrol. 2012 May;7(5):742-7. doi: 10.2215/CJN.06990711. Epub 2012 Mar 8.
- Rondon-Berrios H, Berl T. Mild Chronic Hyponatremia in the Ambulatory Setting: Significance and Management. Clin J Am Soc Nephrol. 2015 Dec 7;10(12):2268-78. doi: 10.2215/CJN.00170115. Epub 2015 Jun 24.
- Schrier RW, Gross P, Gheorghiade M, Berl T, Verbalis JG, Czerwiec FS, Orlandi C; SALT Investigators. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med. 2006 Nov 16;355(20):2099-112. doi: 10.1056/NEJMoa065181. Epub 2006 Nov 14.
- Decaux G, Genette F. Urea for long-term treatment of syndrome of inappropriate secretion of antidiuretic hormone. Br Med J (Clin Res Ed). 1981 Oct 24;283(6299):1081-3. doi: 10.1136/bmj.283.6299.1081.
- Rondon-Berrios H, Tandukar S, Mor MK, Ray EC, Bender FH, Kleyman TR, Weisbord SD. Urea for the Treatment of Hyponatremia. Clin J Am Soc Nephrol. 2018 Nov 7;13(11):1627-1632. doi: 10.2215/CJN.04020318. Epub 2018 Sep 4.
- Gankam-Kengne F, Ayers C, Khera A, de Lemos J, Maalouf NM. Mild hyponatremia is associated with an increased risk of death in an ambulatory setting. Kidney Int. 2013 Apr;83(4):700-6. doi: 10.1038/ki.2012.459. Epub 2013 Jan 16.
- Boscoe A, Paramore C, Verbalis JG. Cost of illness of hyponatremia in the United States. Cost Eff Resour Alloc. 2006 May 31;4:10. doi: 10.1186/1478-7547-4-10.
- Decaux G. Is asymptomatic hyponatremia really asymptomatic? Am J Med. 2006 Jul;119(7 Suppl 1):S79-82. doi: 10.1016/j.amjmed.2006.05.013.
- Renneboog B, Musch W, Vandemergel X, Manto MU, Decaux G. Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits. Am J Med. 2006 Jan;119(1):71.e1-8. doi: 10.1016/j.amjmed.2005.09.026.
- Verbalis JG, Barsony J, Sugimura Y, Tian Y, Adams DJ, Carter EA, Resnick HE. Hyponatremia-induced osteoporosis. J Bone Miner Res. 2010 Mar;25(3):554-63. doi: 10.1359/jbmr.090827.
- Kruse C, Eiken P, Vestergaard P. Hyponatremia and osteoporosis: insights from the Danish National Patient Registry. Osteoporos Int. 2015 Mar;26(3):1005-16. doi: 10.1007/s00198-014-2973-1. Epub 2014 Dec 3.
- Jamal SA, Arampatzis S, Harrison SL, Bucur RC, Ensrud K, Orwoll ES, Bauer DC. Hyponatremia and Fractures: Findings From the MrOS Study. J Bone Miner Res. 2015 Jun;30(6):970-5. doi: 10.1002/jbmr.2383.
- Hoorn EJ, Rivadeneira F, van Meurs JB, Ziere G, Stricker BH, Hofman A, Pols HA, Zietse R, Uitterlinden AG, Zillikens MC. Mild hyponatremia as a risk factor for fractures: the Rotterdam Study. J Bone Miner Res. 2011 Aug;26(8):1822-8. doi: 10.1002/jbmr.380.
- Mohan S, Gu S, Parikh A, Radhakrishnan J. Prevalence of hyponatremia and association with mortality: results from NHANES. Am J Med. 2013 Dec;126(12):1127-37.e1. doi: 10.1016/j.amjmed.2013.07.021.
- Greenberg A, Verbalis JG, Amin AN, Burst VR, Chiodo JA 3rd, Chiong JR, Dasta JF, Friend KE, Hauptman PJ, Peri A, Sigal SH. Current treatment practice and outcomes. Report of the hyponatremia registry. Kidney Int. 2015 Jul;88(1):167-77. doi: 10.1038/ki.2015.4. Epub 2015 Feb 11.
- Decaux G, Gankam Kengne F, Couturier B, Musch W, Soupart A, Vandergheynst F. Mild water restriction with or without urea for the longterm treatment of syndrome of inappropriate antidiuretic hormone secretion (SIADH): Can urine osmolality help the choice? Eur J Intern Med. 2018 Feb;48:89-93. doi: 10.1016/j.ejim.2017.09.024. Epub 2017 Oct 7.
- Decaux G. Treatment of the syndrome of inappropriate secretion of antidiuretic hormone by long loop diuretics. Nephron. 1983;35(2):82-8. doi: 10.1159/000183052. No abstract available.
- Decaux G, Waterlot Y, Genette F, Hallemans R, Demanet JC. Inappropriate secretion of antidiuretic hormone treated with frusemide. Br Med J (Clin Res Ed). 1982 Jul 10;285(6335):89-90. doi: 10.1136/bmj.285.6335.89.
- Decaux G, Waterlot Y, Genette F, Mockel J. Treatment of the syndrome of inappropriate secretion of antidiuretic hormone with furosemide. N Engl J Med. 1981 Feb 5;304(6):329-30. doi: 10.1056/NEJM198102053040605. No abstract available.
- Bhandari S, Peri A, Cranston I, McCool R, Shaw A, Glanville J, Petrakova L, O'Reilly K. A systematic review of known interventions for the treatment of chronic nonhypovolaemic hypotonic hyponatraemia and a meta-analysis of the vaptans. Clin Endocrinol (Oxf). 2017 Jun;86(6):761-771. doi: 10.1111/cen.13315. Epub 2017 Mar 27.
- Jaber BL, Almarzouqi L, Borgi L, Seabra VF, Balk EM, Madias NE. Short-term efficacy and safety of vasopressin receptor antagonists for treatment of hyponatremia. Am J Med. 2011 Oct;124(10):977.e1-9. doi: 10.1016/j.amjmed.2011.04.028.
- Li B, Fang D, Qian C, Feng H, Wang Y. The Efficacy and Safety of Tolvaptan in Patients with Hyponatremia: A Meta-Analysis of Randomized Controlled Trials. Clin Drug Investig. 2017 Apr;37(4):327-342. doi: 10.1007/s40261-016-0470-3. Erratum In: Clin Drug Investig. 2017 Apr;37(4):411-413.
- Rozen-Zvi B, Yahav D, Gheorghiade M, Korzets A, Leibovici L, Gafter U. Vasopressin receptor antagonists for the treatment of hyponatremia: systematic review and meta-analysis. Am J Kidney Dis. 2010 Aug;56(2):325-37. doi: 10.1053/j.ajkd.2010.01.013. Epub 2010 Jun 9.
- Zhang X, Zhao M, Du W, Zu D, Sun Y, Xiang R, Yang J. Efficacy and Safety of Vasopressin Receptor Antagonists for Euvolemic or Hypervolemic Hyponatremia: A Meta-Analysis. Medicine (Baltimore). 2016 Apr;95(15):e3310. doi: 10.1097/MD.0000000000003310.
- Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Grantham JJ, Higashihara E, Perrone RD, Krasa HB, Ouyang J, Czerwiec FS; TEMPO 3:4 Trial Investigators. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2012 Dec 20;367(25):2407-18. doi: 10.1056/NEJMoa1205511. Epub 2012 Nov 3.
- Spasovski G, Vanholder R, Allolio B, Annane D, Ball S, Bichet D, Decaux G, Fenske W, Hoorn EJ, Ichai C, Joannidis M, Soupart A, Zietse R, Haller M, van der Veer S, Van Biesen W, Nagler E; Hyponatraemia Guideline Development Group. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Nephrol Dial Transplant. 2014 Apr;29 Suppl 2:i1-i39. doi: 10.1093/ndt/gfu040. Epub 2014 Feb 25. Erratum In: Nephrol Dial Transplant. 2014 Jun;40(6):924.
- Decaux G, Andres C, Gankam Kengne F, Soupart A. Treatment of euvolemic hyponatremia in the intensive care unit by urea. Crit Care. 2010;14(5):R184. doi: 10.1186/cc9292. Epub 2010 Oct 14.
- Lockett J, Berkman KE, Dimeski G, Russell AW, Inder WJ. Urea treatment in fluid restriction-refractory hyponatraemia. Clin Endocrinol (Oxf). 2019 Apr;90(4):630-636. doi: 10.1111/cen.13930. Epub 2019 Jan 25.
- Nervo A, D'Angelo V, Rosso D, Castellana E, Cattel F, Arvat E, Grossi E. Urea in cancer patients with chronic SIAD-induced hyponatremia: Old drug, new evidence. Clin Endocrinol (Oxf). 2019 Jun;90(6):842-848. doi: 10.1111/cen.13966. Epub 2019 Mar 29.
- Corona G, Giuliani C, Verbalis JG, Forti G, Maggi M, Peri A. Hyponatremia improvement is associated with a reduced risk of mortality: evidence from a meta-analysis. PLoS One. 2015 Apr 23;10(4):e0124105. doi: 10.1371/journal.pone.0124105. eCollection 2015. Erratum In: PLoS One. 2016;11(3):e0152846.
- Vandergheynst F, Gombeir Y, Bellante F, Perrotta G, Remiche G, Melot C, Mavroudakis N, Decaux G. Impact of hyponatremia on nerve conduction and muscle strength. Eur J Clin Invest. 2016 Apr;46(4):328-33. doi: 10.1111/eci.12597. Epub 2016 Feb 23.
- Refardt J, Kling B, Krausert K, Fassnacht M, von Felten S, Christ-Crain M, Fenske W. Impact of chronic hyponatremia on neurocognitive and neuromuscular function. Eur J Clin Invest. 2018 Nov;48(11):e13022. doi: 10.1111/eci.13022. Epub 2018 Sep 19.
- Verbalis JG, Greenberg A, Burst V, Haymann JP, Johannsson G, Peri A, Poch E, Chiodo JA 3rd, Dave J. Diagnosing and Treating the Syndrome of Inappropriate Antidiuretic Hormone Secretion. Am J Med. 2016 May;129(5):537.e9-537.e23. doi: 10.1016/j.amjmed.2015.11.005. Epub 2015 Nov 14.
- Connaboy C, Johnson CD, LaGoy AD, Pepping GJ, Simpson RJ, Deng Z, Ma L, Bower JL, Eagle SR, Flanagan SD, Alfano CA. Intersession Reliability and Within-Session Stability of a Novel Perception-Action Coupling Task. Aerosp Med Hum Perform. 2019 Feb 1;90(2):77-83. doi: 10.3357/AMHP.5190.2019.
- Erickson GB, Citek K, Cove M, Wilczek J, Linster C, Bjarnason B, Langemo N. Reliability of a computer-based system for measuring visual performance skills. Optometry. 2011 Sep;82(9):528-42. doi: 10.1016/j.optm.2011.01.012. Epub 2011 Jun 25.
- Wang L, Krasich K, Bel-Bahar T, Hughes L, Mitroff SR, Appelbaum LG. Mapping the structure of perceptual and visual-motor abilities in healthy young adults. Acta Psychol (Amst). 2015 May;157:74-84. doi: 10.1016/j.actpsy.2015.02.005. Epub 2015 Mar 5.
- Borg FG, Laxaback G. Entropy of balance--some recent results. J Neuroeng Rehabil. 2010 Jul 30;7:38. doi: 10.1186/1743-0003-7-38.
- Kang HG, Costa MD, Priplata AA, Starobinets OV, Goldberger AL, Peng CK, Kiely DK, Cupples LA, Lipsitz LA. Frailty and the degradation of complex balance dynamics during a dual-task protocol. J Gerontol A Biol Sci Med Sci. 2009 Dec;64(12):1304-11. doi: 10.1093/gerona/glp113. Epub 2009 Aug 13.
- Vereeck L, Wuyts F, Truijen S, Van de Heyning P. Clinical assessment of balance: normative data, and gender and age effects. Int J Audiol. 2008 Feb;47(2):67-75. doi: 10.1080/14992020701689688.
- Wallmann HW. Comparison of elderly nonfallers and fallers on performance measures of functional reach, sensory organization, and limits of stability. J Gerontol A Biol Sci Med Sci. 2001 Sep;56(9):M580-3. doi: 10.1093/gerona/56.9.m580.
- Sterns RH, Silver SM, Hix JK. Urea for hyponatremia? Kidney Int. 2015 Feb;87(2):268-70. doi: 10.1038/ki.2014.320.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- STUDY20050035
- R21DK122023 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- ANALYTIC_CODE
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Hyponatremia
-
Otsuka Frankfurt Research Institute GmbHUnknownSIADH | Non-SIADH Hyponatremia | Non-HyponatremiaDenmark, Germany, Italy, Norway, Spain, Sweden, United Kingdom
-
Otsuka America PharmaceuticalRegistrat-MapiCompletedEuvolemic Hyponatremia | Hypervolemic HyponatremiaUnited States, United Kingdom, Germany
-
Korea Otsuka Pharmaceutical Co., Ltd.CompletedHypervolemic and Euvolemic HyponatremiaKorea, Republic of
-
Hospital Italiano de Buenos AiresSociedad Argentina de Hipertension Arterial (SAHA)CompletedThiazide Diuretics Induced HyponatremiaArgentina
-
CardioKine Inc.Biogen; Cardiokine Biopharma, LLCCompletedEuvolemic HyponatremiaUnited States, Israel, India, Mexico, Peru, Belgium, Czech Republic, Italy
-
CardioKine Inc.Biogen; Cardiokine Biopharma, LLCCompletedHyponatremia With Excess Extracellular Fluid Volume | Hyponatremia With Normal Extracellular Fluid VolumeUnited States
-
Jiangsu HengRui Medicine Co., Ltd.Beijing Friendship Hospital; Beijing 302 Hospital; Beijing Anzhen HospitalUnknownNon-hypovolemic Non-acute HyponatremiaChina
-
University of CologneRecruitingNon-hypervolemic HyponatremiaGermany
-
Western States Endurance Run Research FoundationUnknownExercise-associated HyponatremiaUnited States
-
University Hospital, Basel, SwitzerlandRecruitingThiazide-induced Hyponatremia (TIH)Switzerland
Clinical Trials on Urea
-
University of BrasiliaUniversity of WashingtonCompletedRadiodermatitisBrazil
-
Korea University Guro HospitalHanmi Pharmaceutical Company LimitedCompletedHepatocellular CarcinomaKorea, Republic of
-
Galderma R&DCompleted
-
Galderma R&DCompleted
-
University of BrasiliaCompletedRadiodermatitisBrazil
-
Indonesia UniversityCompletedXerosis CutisIndonesia
-
University of AarhusUnknownComparison of Different Concentrations of Carbamide as Moisturizers in Ichthyosis Vulgaris (Urea-IV)Ichthyosis VulgarisDenmark
-
University Children's Hospital, ZurichRecruitingUrea Cycle DisordersSwitzerland
-
ACO Hud Nordic ABUnknown
-
Ivan de Kouchkovsky, MDNational Cancer Institute (NCI); American Cancer Society, Inc.; National Institute...RecruitingProstate CancerUnited States