[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100633567":3},{"organization":4,"outcomesModule":7,"designInfo":32,"detailedDescription":38,"studyPopulation":31,"armGroups":39,"interventions":46,"overallOfficials":31,"centralContacts":31,"locations":52,"responsibleParty":73,"collaborators":31,"id":75,"slug":31,"hasResults":76,"nctId":77,"briefTitle":78,"officialTitle":79,"acronym":80,"eligibilityCriteria":81,"healthyVolunteers":76,"sex":82,"minAge":83,"maxAge":31,"enrollmentInfo":84,"targetDuration":31,"studyType":87,"phases":88,"briefSummary":89,"conditions":90,"keywords":92,"overallStatus":55,"whyStopped":31,"lastUpdateSubmitDate":96,"lastUpdatePostDateStruct":97,"startDateStruct":100,"completionDateStruct":102,"leadSponsor":104,"locationsCount":105},{"fullName":5,"class":6},"University of Turin, Italy","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":31},[9],{"measure":10,"description":11,"timeFrame":12},"Change in serum sodium levels","Change in serum sodium from baseline to assess the acute and chronic effectiveness of urea therapy in outpatients with SIAD not adequately compensated by fluid restriction (≤1500 mL\u002Fday)","Baseline, day 1, day 21±4, day 42±4, and 10±2 days post urea discontinuation",[14,18,21,24,28],{"measure":15,"description":16,"timeFrame":17},"Changes in copeptin, NT-proBNP, and MR-proADM levels","Changes in copeptin, NT-proBNP, and MR-proADM levels from baseline to day 42±4 and after urea discontinuation at 10±2 days, to evaluate chronic neuroendocrine response to urea therapy","Baseline, day 42±4, and 10±2 days post-therapy",{"measure":19,"description":20,"timeFrame":17},"Bioimpedance adaptation","Changes in intra- and extracellular fluid volumes as assessed by bioimpedance vector analysis (BIVA) from baseline to day 42±4 and after urea discontinuation at 10±2 days",{"measure":22,"description":23,"timeFrame":17},"Bone turnover markers","Changes in serum C-terminal telopeptide (CTX) and N-terminal pro-peptide of type 1 collagen (PINP) from baseline to day 42±4 and after urea discontinuation at 10±2 days, to evaluate bone metabolism response to variation of serum sodium levels",{"measure":25,"description":26,"timeFrame":27},"Cognitive performance","Changes in Montreal Cognitive Assessment (MoCA) scores from baseline to day 42±4, to evaluate the effect of sodium increase normalization on cognitive function","Baseline and day 42±4",{"measure":29,"description":30,"timeFrame":12},"Variation in other Serum and Urinary Analytes","Blood (potassium, creatinine, urea, uric acid, glucose, plasma osmolality) and urine analytes (potassium, creatinine, urea, uric acid, urine osmolality, and fractional excretion of sodium, potassium, urea, and uric acid) will be assessed at baseline, day 1, day 21±4, day 42±4, and 10±2 days post-therapy to evaluate changes following initiation and discontinuation of urea supplementation, and to explore potential predictors of treatment response and remission of hyponatremia",null,{"allocation":33,"interventionModel":34,"interventionModelDescription":31,"primaryPurpose":35,"observationalModel":31,"timePerspective":31,"maskingInfo":36},"NA","SINGLE_GROUP","TREATMENT",{"masking":37,"maskingDescription":31,"whoMasked":31},"NONE","Hyponatremia (serum sodium, s-Na \\\u003C135 mmol\u002FL) is the most common electrolyte disorder in hospitalized patients, with prevalence increasing with length of hospital stay. Among hypotonic euvolemic hyponatremias, the syndrome of inappropriate antidiuresis (SIAD) is the most frequent cause and is characterized by impaired free water excretion. SIAD may result from central nervous system disorders, pulmonary diseases, malignancies, or medications, and remains a diagnosis of exclusion.\n\nWhen possible, treating the underlying cause can resolve the syndrome; however, in many cases the cause remains unknown and therapeutic options are limited. First-line treatment is fluid restriction, which is often insufficient and difficult to maintain in the long term. AVP receptor antagonists, such as tolvaptan, are effective but expensive and may carry a risk of overly rapid correction of serum sodium.\n\nSecond-line therapy recommended by current guidelines is urea supplementation, which has shown safety and efficacy in normalizing serum sodium. However, most available evidence derives from retrospective studies, and prospective data are limited.\n\nThis study aims to evaluate the effectiveness of urea supplementation in patients with chronic, mildly symptomatic SIAD-related hyponatremia not adequately controlled by fluid restriction (≤1500 mL\u002Fday), and to explore its effects on neuroendocrine adaptation, body fluid composition, and bone metabolism.",[40],{"label":41,"type":42,"description":43,"interventionNames":44},"Urea therapy","EXPERIMENTAL","Participants will receive oral urea supplementation for 42±4 days, followed by a 10±2-day washout period",[45],"Dietary Supplement: urea",[47],{"type":48,"name":49,"description":50,"armGroupLabels":51,"otherNames":31},"DIETARY_SUPPLEMENT","urea","Patients with persistent hyponatremia (sodium corrected for glucose \\\u003C135 mmol\u002FL) after ≥1 week of fluid restriction (≤1500 mL\u002Fday) will receive urea 30 g\u002Fday (2 sachets; 1 in the morning and 1 in the evening) dissolved in water, while maintaining fluid restriction ≤1500 mL\u002Fday.\n\nBlood and urine evaluations will be performed at day 1, day 21±4 and day 42±4, with additional assessments (Montreal Cognitive Assessment \\[MoCA\\] questionnaire and bioelectrical impedance vector analysis \\[BIVA\\]) at selected visits.\n\nUrea dose adjustments will be based on serum sodium at day 21±4: 45 g\u002Fday if Na 130-134 mmol\u002FL, or 60 g\u002Fday if Na \\\u003C130 mmol\u002FL (maximum 60 g\u002Fday).\n\nIn case of intolerance, the dose will be reduced by one sachet from the planned dose.\n\nAfter day 42±4, urea will be discontinued. A final evaluation will be performed 10±2 days after discontinuation.",[41],[53],{"facility":54,"status":55,"city":56,"state":57,"zip":58,"country":59,"countryCode":60,"cosmosGeoPoint":61,"geoPoint":66,"contacts":67},"AOU Città della Salute e della Scienza","RECRUITING","Turin","Piedmont, Italy","10126","Italy","IT",{"type":62,"coordinates":63},"Point",[64,65],7.68682,45.07049,{"lat":65,"lon":64},[68],{"name":69,"role":70,"phone":71,"phoneExt":31,"email":72},"Silvia Grottoli, Professor","CONTACT","+390116337400","silvia.grottoli@unito.it",{"type":74,"investigatorFullName":31,"investigatorTitle":31,"investigatorAffiliation":31,"oldNameTitle":31,"oldOrganization":31},"SPONSOR","100633567",false,"NCT07528365","Urea for Treatment of Hyponatremia in Patients With SIAD Unresponsive to Fluid Restriction","Efficacy of Oral Urea Supplementation in Patients With SIAD Not Adequately Controlled With Fluid Restriction","UREA-BIVA","Inclusion Criteria:\n\n* Confirmed diagnosis of SIAD established prior to study inclusion, defined as:\n* Plasma sodium concentration \\\u003C135 mmol\u002FL\n* Plasma osmolality \\\u003C300 mOsm\u002Fkg\n* Urine osmolality \\>100 mOsm\u002Fkg\n* Urine sodium concentration \\>30 mmol\u002FL\n* Intact adrenal and thyroidal function and no use of diuretics in the last 4 weeks\n* Clinical euvolemia, defined as an absence of signs of hypovolemia (orthostasis, tachycardia, decreased skin turgor, dry mucous membranes) or hypervolemia (edema, ascites)\n\nFulfillment of all diagnostic criteria at baseline (day 0) was not mandatory, as the diagnosis of SIAD had already been established prior to study inclusion based on overall clinical assessment.\n\n\\- Written informed consent obtained\n\nExclusion Criteria:\n\n* Chronic hypotonic hyponatremia secondary to another etiology\n* Presence of moderate to severe symptoms attributable to plasma hypotonicity\n* Severe hypotonic hyponatremia (serum sodium \\\u003C120 mmol\u002FL)\n* Another ongoing drug treatment for hyponatremia (including vaptans and salt tablets)\n* Severe hepatic insufficiency\n* eGFR \\\u003C45 mL\u002Fmin\u002F1.73 m²\n* Pregnancy or breastfeeding\n* Known allergy or intolerance to urea\n* Patient refusal or inability to provide written informed consent","ALL","18 Years",{"count":85,"type":86},20,"ESTIMATED","INTERVENTIONAL",[33],"Hyponatremia due to SIAD is frequently insufficiently corrected by fluid restriction alone, which remains the first-line therapy but is often poorly tolerated. Urea supplementation is recommended as second-line therapy.\n\nThis prospective study evaluates the effectiveness of oral urea supplementation in patients with chronic SIAD and persistent hyponatremia despite fluid restriction.",[91],"SIAD - Syndrome of Inappropriate Antidiuresis",[93,49,94,95],"hyponatremia","plasma sodium level","SIAD","2026-04-07",{"date":98,"type":99},"2026-04-14","ACTUAL",{"date":101,"type":99},"2024-09-12",{"date":103,"type":86},"2027-12",{"name":5,"class":6},1]