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The aim of this study is to evaluate whether a new test using mannitol infusion can diagnose the cause of polyuria-polydipsia syndrome as accurately as the current standard test (hypertonic saline infusion) and to compare which test patients prefer. The goal is to identify a simpler and more patient-friendly diagnostic approach.
Polyuria-polydipsia syndrome (PPS), characterized by excessive urination and fluid intake, can have different underlying causes, including a deficiency of the hormone vasopressin (AVP-D) or excessive fluid intake without AVP-D (primary polydipsia). Correctly identifying the cause is essential, as the treatments differ and an incorrect diagnosis can negatively impact patient care.
A blood marker called copeptin is used to support the diagnosis, as it reflects vasopressin levels in the body. Currently, the most accurate method involves measuring copeptin after stimulation with hypertonic saline. However, this test is complex, requires close medical monitoring, and can be uncomfortable for patients.
Mannitol is a substance already used in routine clinical care and may offer a simpler way to stimulate copeptin release. Early results suggest that it could provide similar diagnostic accuracy with fewer side effects and better patient comfort.
This study is a randomized, cross-over, multicenter trial in which participants undergo both tests (mannitol and hypertonic saline) in random order. The study compares the diagnostic accuracy and patient preference for both methods, as well as safety and tolerability. In addition, it explores whether other clinical and laboratory measures can further improve the diagnosis of PPS.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Mannitol Infusion | Experimental | Diagnostic evaluation of polyuria polydipsia syndrome through copeptin measurement after mannitol infusion. |
|
| Hypertonic Saline Infusion (HIS) | Active Comparator | Diagnostic evaluation of polyuria polydipsia syndrome through copeptin measurement after HIS |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mannitol | Diagnostic Test | Intravenous infusion of 1.5g/kg body weight (max. 120g) mannitol is given over 30 minutes (≙ 7.5ml/kg body weight). |
|
| Measure | Description | Time Frame |
|---|---|---|
| Overall Diagnostic Accuracy | The overall diagnostic accuracy is defined as the proportion of correct diagnoses out of all diagnoses based on the stimulated copeptin value. Final diagnosis will be made after termination of the study by two endocrine specialists who will be blinded to the copeptin results of the mannitol infusion. | One time assessment at Follow up Visit 2 (10 weeks after baseline) |
| Patient Test Preference | Patient-reported preference between mannitol infusion and hypertonic saline infusion, assessed using a 5-point Likert scale ranging from -2 (strong preference for hypertonic saline) to +2 (strong preference for mannitol). | 1 week after completion of both diagnostic tests |
| Measure | Description | Time Frame |
|---|---|---|
| Diagnostic Performance Measures for AVP-D | Sensitivity, specificity, positive predictive value, and negative predictive value of mannitol infusion and hypertonic saline infusion for diagnosing AVP deficiency using predefined copeptin cut-offs. | At completion of follow-up, 10 weeks after last diagnostic test |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Talitha Hildebrandt | Contact | +41 61 55 65075 | talithanatalja.hildebrandt@usb.ch | |
| Cemile Bathelt | Contact | +41 61 55 65407 | cemile.bathelt@usb.ch |
| Name | Affiliation | Role |
|---|---|---|
| Mirjam Christ-Crain, Prof. Dr. | University Hospital of Basel | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Basel | Recruiting | Basel | 4031 | Switzerland |
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| ID | Term |
|---|---|
| D020790 | Diabetes Insipidus, Neurogenic |
| D059607 | Polydipsia, Psychogenic |
| D003919 | Diabetes Insipidus |
| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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Randomized open-label cross-over diagnostic multicenter study
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| Hypertonic Saline | Diagnostic Test | Intravenous infusion of NaCl 3% is given first as a bolus of 250ml over 15 minutes, then with an infusion rate of 0.15ml/kg body weight / minute (≙ 9ml/kg body weight/hour). |
|
| Diagnostic Performance Measures for PP |
Sensitivity, specificity, positive predictive value, and negative predictive value of mannitol infusion and hypertonic saline infusion for diagnosing PP using predefined copeptin cut-offs. |
| At completion of follow-up, 10 weeks after last diagnostic test |
| Optimal copeptin cut-off after mannitol infusion | Exploratory determination and validation of optimal copeptin cut-off values for differentiating AVP deficiency from primary polydipsia following mannitol stimulation. | At completion of follow-up, 10 weeks after last diagnostic test |
| Frequency and severity of clinical symptoms | Frequency and severity of symptoms (e.g., thirst, headache, nausea, malaise) assessed using numeric rating scales during mannitol and hypertonic saline tests. | During each test day (baseline to end of monitoring period 90 minutes/ 240 minutes) |
| Subjective burden of each test assessed by numeric rating scale | Patient-reported burden of each diagnostic test assessed using a numeric rating scale (NRS) (0-10). | Immediately after each test day |
| Psychopathological assessment (STAI-T) | General anxiety levels is assessed by State-Trait Anxiety Inventory (STAI-T) questionnaire. The total trait score (STAI-T) ranges from 20 to 80, with higher scores indicating more pronounced anxiety. | Baseline |
| Autistic traits | Autistic traits is assessed by Autism-Spectrum Quotient (AQ) questionnaire. The AQ consists of 50 items, with four choices for each item from "definitely agree" to "definitely disagree" and a total score from 0 to 50. A score above the proposed cut-off of 29 highlights significant traits of autism. | Baseline |
| Quality of Life in Posterior Pituitary Disease | Currently, no disease-specific tool exists to assess treatment success for either desmopressin or oxytocin (OXT) therapy in patients with arginine vasopressin deficiency (AVP-D). To address this gap, we developed a novel multidimensional questionnaire in close collaboration with patients, patient representatives, and patient advocates. The PP-QoL consists of three parts: Part A assesses symptoms related to AVP-D (15 items), while Parts B (17 items) and C (21 items) focus on domains associated with OXT deficiency. | Baseline and follow-up (10 weeks ) |
| Change in oxytocin/neurophysin I levels | Change in circulating oxytocin and neurophysin I levels before and after each diagnostic test. | Baseline and 90 minutes post-stimulation |
| Spearman's rank correlation coefficient between psychopathology questionnaires and oxytocin levels | Correlation between psychopathological questionnaires and oxytocin levels will be described using Spearman's rank correlation coefficient. | Baseline and 90 minutes post-stimulation |
| Spearman's rank correlation coefficient between psychopathology questionnaire and neurophysin I levels | Correlation between psychopathological questionnaires and neurophysin I levels will be described using Spearman's rank correlation coefficient. | Baseline and 90 minutes post-stimulation |
| Validation of clinical diagnostic score | Validation of a predefined diagnostic score using clinical and basal parameters | After test day 2 and 10 weeks thereafter |
| Change of urinary copeptin levels | Change in urinary copeptin levels before and after mannitol and hypertonic saline stimulation. | During test day 1 and test day 2 with a maximum of 3 month in between the two test days |
| Optimal urinary copeptin cut-offs | Exploratory determination of optimal urinary copeptin thresholds for differential diagnosis. | 10 weeks after test day 2 |
| Sex-specific copeptin response | Evaluation of sex-specific differences in stimulated copeptin levels and corresponding diagnostic cut-offs. | During test day 1 and test day 2 with a maximum of 3 month in between the two test days and at study completion |
| Cost-efficiency of diagnostic tests | Exploratory assessment of healthcare costs associated with mannitol infusion versus hypertonic saline infusion. | One time assessment at Follow up Visit 2 (10 weeks after baseline) |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D010900 | Pituitary Diseases |
| D004700 | Endocrine System Diseases |
| D059606 | Polydipsia |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012816 | Signs and Symptoms |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |