Arginine Vasopressin DeficiencyCOMPASSNCT07569861
Copeptin Measurement After Mannitol and Hypertonic Saline for the Diagnosis of Polyuria-polydipsia Syndrome
A study testing Mannitol and Hypertonic Saline in people with Arginine Vasopressin Deficiency and Primary Polydipsia, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Arginine Vasopressin Deficiency, Primary Polydipsia
- What is being tested?
- Mannitol and Hypertonic Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 144 participants
- Where
- 1 siteSwitzerland
- Study dates
- 16 Jun 2026to Jun 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- Age ≥ 18 years
- Hypotonic polyuria/polydipsia syndrome defined as polyuria >40ml/kg body weight/24h and polydipsia >3l/24h; and urine osmolality <800mOsm/L or known AVP-D based on accepted criteria
Who cannot join
- Polyuria/polydipsia secondary to diabetes mellitus, hypercalcemia, or hypokalemia
- Diagnosis of AVP-R (Copeptin > 21.4 pmol/L)
- Evidence of acute illness
- Epilepsy requiring treatment
- Uncontrolled arterial hypertension (blood pressure >160/100mmHg at baseline
- eGFR < 60 ml/min/1,73 m2
Show all 14Show fewer
- Cardiac failure (NYHA III-IV)
- Diagnosis of liver cirrhosis, Child-Pugh Class C
- Uncorrected adrenal or thyroidal deficiency
- Pregnancy or breastfeeding
- Current or unresolved urinary obstruction
- Enrollment in a clinical trial within the last 30 days
- Patients refusing or unable to give written informed consent
- Inability to follow study procedures
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland1 site, 1 recruiting
- Recruiting
University Hospital Basel
Basel, 4031
Talitha Hildebrandt, +41 61 55 65075, talithanatalja.hildebrandt@usb.ch
Mirjam Christ-Crain, Prof. Dr.
About this study
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.
Read the detailed description
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.
- Being tested
- Mannitol, Hypertonic Saline
- Keywords
- Copeptin Measurement, Diagnosis of Polyuria-polydipsia syndrome, Mannitol, Hypertonic Saline Infusion
- Medical subject headings
- Diabetes Insipidus, Neurogenic, Polydipsia, Psychogenic, Diabetes Insipidus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MannitolDiagnostic test
Intravenous infusion of 1.5g/kg body weight (max. 120g) mannitol is given over 30 minutes (≙ 7.5ml/kg body weight).
Hypertonic SalineDiagnostic 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).
| Study group | Role | What they receive |
|---|---|---|
| Mannitol Infusion | Experimental | Diagnostic evaluation of polyuria polydipsia syndrome through copeptin measurement after mannitol infusion. Receives: Diagnostic Test: Mannitol |
| Hypertonic Saline Infusion (HIS) | Active comparator | Diagnostic evaluation of polyuria polydipsia syndrome through copeptin measurement after HIS Receives: Diagnostic Test: Hypertonic Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 1 week after completion of both diagnostic tests
Secondary outcomes (16)
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.
Measured: At completion of follow-up, 10 weeks after last diagnostic test
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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline and 90 minutes post-stimulation
Validation of clinical diagnostic score
Validation of a predefined diagnostic score using clinical and basal parameters
Measured: 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.
Measured: 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.
Measured: 10 weeks after test day 2
Sex-specific copeptin response
Evaluation of sex-specific differences in stimulated copeptin levels and corresponding diagnostic cut-offs.
Measured: 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.
Measured: One time assessment at Follow up Visit 2 (10 weeks after baseline)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2026
- Study start16 Jun 2026
- Primary completionJun 2030 (estimated)
- Study completionJun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Arginine Vasopressin DeficiencyStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized open-label cross-over diagnostic multicenter study
- Masking
- None (open label)
- Enrolment
- 144 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mirjam Christ-Crain, Prof. Dr., Study chair, University Hospital of Basel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07569861
- Sponsor's protocol ID
- 2026-00480;kt25ChristCrain7
- Acronym
- COMPASS
- Status last verified
- Jun 2026
- First submitted
- 30 Mar 2026
- Last updated
- 18 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Copeptin Measurement After Mannitol and Hypertonic Saline for the Diagnosis of Polyuria-polydipsia Syndrome
- ClinicalTrials.gov ID
- NCT07569861
- Acronym / sponsor ID
- COMPASS / 2026-00480;kt25ChristCrain7
- Keywords
- Copeptin Measurement, Diagnosis of Polyuria-polydipsia syndrome, Mannitol, Hypertonic Saline Infusion
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 144 participants (estimated)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- 16 Jun 2026 (actual)
- Primary completion
- Jun 2030 (estimated)
- Study completion
- Jun 2030 (estimated)
- First posted
- 6 May 2026 (actual)
- 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.
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.
Detailed description
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized open-label cross-over diagnostic multicenter study
| Arm | Type | Receives |
|---|---|---|
| Mannitol Infusion | Experimental | Diagnostic Test: MannitolDiagnostic evaluation of polyuria polydipsia syndrome through copeptin measurement after mannitol infusion. |
| Hypertonic Saline Infusion (HIS) | Active comparator | Diagnostic Test: Hypertonic SalineDiagnostic evaluation of polyuria polydipsia syndrome through copeptin measurement after HIS |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age ≥ 18 years
- Hypotonic polyuria/polydipsia syndrome defined as polyuria >40ml/kg body weight/24h and polydipsia >3l/24h; and urine osmolality <800mOsm/L or known AVP-D based on accepted criteria
Key exclusion criteria (14 listed)
- Polyuria/polydipsia secondary to diabetes mellitus, hypercalcemia, or hypokalemia
- Diagnosis of AVP-R (Copeptin > 21.4 pmol/L)
- Evidence of acute illness
- Epilepsy requiring treatment
- Uncontrolled arterial hypertension (blood pressure >160/100mmHg at baseline
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 |
|---|---|---|
| MannitolIntravenous infusion of 1.5g/kg body weight (max. 120g) mannitol is given over 30 minutes (≙ 7.5ml/kg body weight). | Diagnostic test | Mannitol Infusion |
| Hypertonic SalineIntravenous 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 test | Hypertonic Saline Infusion (HIS) |
Primary outcome
Overall Diagnostic Accuracy
Time frame: One time assessment at Follow up Visit 2 (10 weeks after baseline)
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.
Patient Test Preference
Time frame: 1 week after completion of both diagnostic tests
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).
16 secondary outcomes
Diagnostic Performance Measures for AVP-D
Time frame: At completion of follow-up, 10 weeks after last diagnostic test
Diagnostic Performance Measures for PP
Time frame: At completion of follow-up, 10 weeks after last diagnostic test
Optimal copeptin cut-off after mannitol infusion
Time frame: At completion of follow-up, 10 weeks after last diagnostic test
Frequency and severity of clinical symptoms
Time frame: During each test day (baseline to end of monitoring period 90 minutes/ 240 minutes)
Subjective burden of each test assessed by numeric rating scale
Time frame: Immediately after each test day
Psychopathological assessment (STAI-T)
Time frame: Baseline
Autistic traits
Time frame: Baseline
Quality of Life in Posterior Pituitary Disease
Time frame: Baseline and follow-up (10 weeks )
Change in oxytocin/neurophysin I levels
Time frame: Baseline and 90 minutes post-stimulation
Spearman's rank correlation coefficient between psychopathology questionnaires and oxytocin levels
Time frame: Baseline and 90 minutes post-stimulation
Spearman's rank correlation coefficient between psychopathology questionnaire and neurophysin I levels
Time frame: Baseline and 90 minutes post-stimulation
Validation of clinical diagnostic score
Time frame: After test day 2 and 10 weeks thereafter
Change of urinary copeptin levels
Time frame: 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
Time frame: 10 weeks after test day 2
Sex-specific copeptin response
Time frame: 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
Time frame: One time assessment at Follow up Visit 2 (10 weeks after baseline)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2026.
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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.
Mirjam Christ-Crain, Prof. Dr. study chair
University Hospital of Basel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Mannitol and Hypertonic Saline in people with Arginine Vasopressin Deficiency and Primary Polydipsia, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
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 2 inclusion and 14 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: looking for participants now, as of the sponsor's last update on 18 Jun 2026. 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 Switzerland. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Talitha Hildebrandt (+41 61 55 65075, talithanatalja.hildebrandt@usb.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Diagnostic Accuracy (time frame: One time assessment at Follow up Visit 2 (10 weeks after baseline)). The study lists 2 primary outcomes in all. 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 18 Jun 2026.