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NCT Number: NCT07569861

Copeptin Measurement After Mannitol and Hypertonic Saline for the Diagnosis of Polyuria-polydipsia Syndrome

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.

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Key information

Conditions

Arginine Vasopressin Deficiency Behavior Behavioral Symptoms Diabetes Insipidus Diabetes Insipidus, Neurogenic Endocrine System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Male Urogenital Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Pituitary Diseases Polydipsia Polydipsia, Psychogenic Primary Polydipsia Signs and Symptoms Urogenital Diseases Urologic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University Hospital Basel

Basel, 4031, Switzerland

Location status: Recruiting

Location contact

Mirjam Christ-Crain, Prof. Dr.

PRINCIPAL_INVESTIGATOR

Talitha Hildebrandt

CONTACT

[email protected]

+41 61 55 65075

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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
  • 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

Treatment and study plan

Mannitol

Diagnostic Test

Intravenous infusion of 1.5g/kg body weight (max. 120g) mannitol is given over 30 minutes (≙ 7.5ml/kg body weight).

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).

Primary outcomes

  1. 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.

  2. 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).

Secondary outcomes

  1. Diagnostic Performance Measures for AVP-D

    Time frame: At completion of follow-up, 10 weeks after last diagnostic test

    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.

  2. Diagnostic Performance Measures for PP

    Time frame: At completion of follow-up, 10 weeks after last diagnostic test

    Sensitivity, specificity, positive predictive value, and negative predictive value of mannitol infusion and hypertonic saline infusion for diagnosing PP using predefined copeptin cut-offs.

  3. Optimal copeptin cut-off after mannitol infusion

    Time frame: At completion of follow-up, 10 weeks after last diagnostic test

    Exploratory determination and validation of optimal copeptin cut-off values for differentiating AVP deficiency from primary polydipsia following mannitol stimulation.

  4. Frequency and severity of clinical symptoms

    Time frame: During each test day (baseline to end of monitoring period 90 minutes/ 240 minutes)

    Frequency and severity of symptoms (e.g., thirst, headache, nausea, malaise) assessed using numeric rating scales during mannitol and hypertonic saline tests.

  5. Subjective burden of each test assessed by numeric rating scale

    Time frame: Immediately after each test day

    Patient-reported burden of each diagnostic test assessed using a numeric rating scale (NRS) (0-10).

  6. Psychopathological assessment (STAI-T)

    Time frame: Baseline

    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.

  7. Autistic traits

    Time frame: Baseline

    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.

  8. Quality of Life in Posterior Pituitary Disease

    Time frame: Baseline and follow-up (10 weeks )

    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.

  9. Change in oxytocin/neurophysin I levels

    Time frame: Baseline and 90 minutes post-stimulation

    Change in circulating oxytocin and neurophysin I levels before and after each diagnostic test.

  10. Spearman's rank correlation coefficient between psychopathology questionnaires and oxytocin levels

    Time frame: Baseline and 90 minutes post-stimulation

    Correlation between psychopathological questionnaires and oxytocin levels will be described using Spearman's rank correlation coefficient.

  11. Spearman's rank correlation coefficient between psychopathology questionnaire and neurophysin I levels

    Time frame: Baseline and 90 minutes post-stimulation

    Correlation between psychopathological questionnaires and neurophysin I levels will be described using Spearman's rank correlation coefficient.

  12. Validation of clinical diagnostic score

    Time frame: After test day 2 and 10 weeks thereafter

    Validation of a predefined diagnostic score using clinical and basal parameters

  13. 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

    Change in urinary copeptin levels before and after mannitol and hypertonic saline stimulation.

  14. Optimal urinary copeptin cut-offs

    Time frame: 10 weeks after test day 2

    Exploratory determination of optimal urinary copeptin thresholds for differential diagnosis.

  15. 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

    Evaluation of sex-specific differences in stimulated copeptin levels and corresponding diagnostic cut-offs.

  16. Cost-efficiency of diagnostic tests

    Time frame: One time assessment at Follow up Visit 2 (10 weeks after baseline)

    Exploratory assessment of healthcare costs associated with mannitol infusion versus hypertonic saline infusion.

Study contacts

Contact information is provided by the study sponsor or research team.

Cemile Bathelt

CONTACT

[email protected]

+41 61 55 65407

Talitha Hildebrandt

CONTACT

[email protected]

+41 61 55 65075

Sponsors and collaborators

Lead sponsor

University Hospital, Basel, Switzerland

Other

Registry information

Acronym: COMPASS

Important dates

Study start
2026
Primary completion
2030
Study completion
2030
First posted
May 6, 2026
Registry last updated
Jun 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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