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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT04588207
Other study ID # STUDY20050035
Secondary ID R21DK122023
Status Terminated
Phase Phase 2
First received
Last updated
Start date December 28, 2021
Est. completion date September 29, 2022

Study information

Verified date April 2024
Source University of Pittsburgh
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This study is examining how a dietary supplement called urea can be used to treat low blood sodium level. Low blood sodium level is a common problem and some studies show that many patients with low blood sodium level suffer from brain fog and/or loss of balance. Unfortunately, it is unknown at this point what the best treatment is for low blood sodium level. With this pilot research study, the investigators are hoping to learn more about whether urea is safe to take, whether patients can tolerate taking urea for several weeks, whether urea increases blood sodium level, and whether urea can help prevent the brain fog and/or loss of balance that some patients with low blood sodium level suffer from. The information obtained with this study is intended to be used to design a larger study in the future to get a definite answer whether urea is beneficial for patients with low blood sodium level.


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.


Recruitment information / eligibility

Status Terminated
Enrollment 2
Est. completion date September 29, 2022
Est. primary completion date September 29, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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: 1. Hyponatremia with a PNa between 125 mmol/L and 132 mmol/L 2. Plasma osmolality < 275 mOsm/kg 3. Clinical euvolemia 4. Urine osmolality > 100 mosm/kg 5. Urine Na = 20 mmol/L 6. Intact adrenal function (i.e., morning plasma cortisol value =15 µg/dL, or negative corticotropin stimulation test) 7. Normal thyroid stimulating hormone (TSH) level (i.e., TSH between 0.3 to 5 µIU/mL) 8. 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 Design


Related Conditions & MeSH terms


Intervention

Drug:
Urea
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.

Locations

Country Name City State
United States University of Pittsburgh Medical Center Pittsburgh Pennsylvania

Sponsors (2)

Lead Sponsor Collaborator
Helbert Rondon Berrios, MD, MS National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (41)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Sterns RH, Silver SM, Hix JK. Urea for hyponatremia? Kidney Int. 2015 Feb;87(2):268-70. doi: 10.1038/ki.2014.320. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 41 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Number and Percentage of Participants Who Met Inclusion/Exclusion Criteria and Were Enrolled in the Study Number and percentage of participants who met inclusion/exclusion criteria and were enrolled in the study. To be assessed by analysis of enrollment data. 9 months
Primary Number and Percentage of Participants Enrolled Who Completed the Study Number and percentage of participants enrolled who completed the study. To be assessed by analysis of enrollment and completion data. 9 months
Primary Monthly Enrollment Rate Number of participants enrolled in the study every month. To be assessed by analysis of enrollment data 9 months
Primary Number of Prescribed Urea Doses Taken by Participants 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
Primary Reasons for Non-Adherence to Urea Therapy 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
Primary Change in Plasma Sodium Concentration Change in plasma sodium concentration from baseline to day 42. Based on plasma sodium assessments on days 0 and 42. Baseline to day 42
Primary Change in Percentage Accuracy Action Boundary Selection 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. Accuracy of affordance perception is measured. Scores goes from 0% to 100% with higher score representing increased accuracy Baseline to day 42
Primary Change in Overall Score of Sensorimotor Ability Battery 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. Score goes from 0 to1500 with higher scores representing better sensorimotor ability Baseline to day 42
Primary Change in the Sample Entropy of the Center of Pressure Data From the Force Plate Measure the 'structure' of the noise in the oscillations of the center of mass of the individual. The measurement represent the percentage of displacement from the center of pressure. No reference ranges are available as these vary according to the population studied Baseline to day 42
Primary Change in Percentage Angular Deviation of Vestibular Control System Using Dynamic Representation of Upright Stance Change in percentage angular deviation of vestibular control system using dynamic representation of upright stance from baseline to day 42. This was 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. No reference range for changes in percentage exist which vary with the population studied. Larger positive changes indicate significant improvement in vestibular balance control. Baseline to day 42
Primary Change in Percentage Angular Deviation of Somatosensory Control System Using Dynamic Representation of Upright Stance 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. No reference range for changes in percentage exist which vary with the population studied. Larger positive changes indicate significant improvement in somatosensory balance control. Baseline to day 42
Primary Change in Percentage Angular Deviation of Visual Control System Using Dynamic Representation of Upright Stance 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. No reference range for changes in percentage exist which vary with the population studied. Larger positive changes indicate significant improvement in visual balance control. Baseline to 42 days
Primary Change in Percentage Weight Symmetry Using Dynamic Representation of Upright Stance 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. Weight symmetry indicates weight distribution under the left and right legs prior to perturbation onset. A score of 100 indicates perfect between-limb symmetry. Larger deviations away (higher or Lower) from 100 indicate asymmetry. Scores goes from -100 to +100 closer to 100 is optimal. Baseline to day 42
Primary Change in Movement Latency of Posture Control and Stability Using Dynamic Representation of Upright Stance 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. Latency scores measure the time lapse between force plate translation on postural response for healthy, elderly populations, with previously reported mean latency values ranging from 126.80-131.40. Higher/Larger scores indicate poorer balance control. Baseline to day 42
Primary Change in Amplitude Scaling of Posture Control and Stability Using Dynamic Representation of Upright Stance 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. It is scored in units of angular momentum and normalized to body height and weight. No reference range for changes in percentage exist which vary with the population studied. Larger positive changes indicate significant improvement in ability to recover from an unexpected external translation reflecting better balance. Baseline to day 42
Primary Number and Proportion of Participants Enrolled in the Study With Adverse Events Related to the Use of 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
Primary Adverse Events Related to 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 Number of Patients Screened Number of patients screened. To be assessed by analysis of screening data. 9 months
Secondary Number and Percentage of Patients Screened Who Met Inclusion/Exclusion Criteria for the Study Number and percentage of patients screened who met inclusion/exclusion criteria for the study.
To be assessed by analysis of screening and enrollment data.
9 months
Secondary Number and Proportion of Participants Who Took More Than 80 Percent of Prescribed Urea Doses 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
Secondary Number and Proportion of Participants Who Thought the Medication Was Acceptable 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
Secondary Average Ratings for Medication Acceptability Average ratings using a 5-point Likert scale 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. A higher overall score represents more acceptability Baseline to day 42 while taking urea
Secondary Change in SF-12 (Health Survey) Mental Component Summary (MCS) 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
Secondary Change in SF-12 (Health Survey) Physical Component Summary (PCS) 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
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