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NCT Number: NCT06542198

Mannitol-induced Release of Copeptin in Healthy Adults and Patients With Polyuria-Polydipsia Syndrome (MARS Study)

The aims of this study are to investigate whether mannitol stimulates copeptin (part 1: proof-of-concept) and whether the copeptin levels upon mannitol infusion differ in primary polydipsia and arginine vasopressin deficiency (part 2: pilot study).

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Key information

Conditions

Polyuria-polydipsia Syndrome 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

About this study

Diagnosing polyuria-polydipsia syndrome, which includes arginine vasopressin (AVP) deficiency (AVP-D, formerly central diabetes insipidus) and primary polydipsia (PP), is challenging but essential. Currently, the most accurate test currently involves measuring copeptin after osmotic stimulation with hypertonic saline, but this test is rarely used due to the need for close sodium monitoring and the discomfort it can cause.

Mannitol has been shown to stimulate AVP release, but no study has tested copeptin levels after mannitol stimulation in healthy adults or patients with AVP-D or PP.

This single-center study is conducted in two consecutive parts. Part 1 is a double-blind, randomized cross-over proof-of-concept study in healthy adults to investigate if mannitol infusion stimulates copeptin release. Part 2 is an open-label, single arm case-control pilot study in adults with diagnosed PP or AVP-D to see if copeptin levels after mannitol stimulation differ in PP and AVP-D.

The results of this study aim to demonstrate if mannitol infusion has the potential to be used as an alternative to hypertonic saline infusion.

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

Part 1: Proof of Concept in Healthy adults

  • Age ≥ 18 years
  • Healthy with no medication except hormonal contraception

Part 2: Pilot Study in Patients with primary polydipsia (PP) or arginine vasopressin deficiency (AVP-D)

  • Age ≥ 18 years
  • Evidence of polyuria > 40-50 ml/kg body weight per 24 hours and polydipsia > 3 Liter per 24 hours or regular desmopressin medication corresponding to a diagnosis of PP or AVP-D

Exclusion criteria

Part 1: Proof of Concept in Healthy adults

  • Participation in a trial with investigational drugs within 30 days
  • Evidence of disordered drinking habits and diuresis defined as polyuria > 40-50 ml/kg body weight per 24 hours and polydipsia > 3 Liter per 24 hours.
  • Estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1,73 m2
  • Glucose > 11.1 mmol/L corresponding to the diagnosis of an uncontrolled diabetes mellitus
  • History of urinary tract obstruction
  • Problems with urination
  • Pregnancy or breastfeeding
  • Multiple allergies (≥ 3)
  • Evidence of acute illness

Part 2: Pilot Study in Patients with PP or AVP-D

  • Participation in a trial with investigational drugs within 30 days
  • Pregnancy or breastfeeding
  • Evidence of acute illness
  • eGFR < 60 ml/min/1,73 m2
  • Glucose > 11.1 mmol/L corresponding to the diagnosis of uncontrolled diabetes mellitus
  • History of urinary tract obstruction
  • Problems with urination
  • Therapy with diuretics
  • Multiple allergies (≥ 3)

Treatment and study plan

Mannitol Infusion (blinded)

Diagnostic Test

1 g of mannitol per kg body weight is infused in 30 minutes (≙ 5 ml/kg body weight), with an upper limit of 80 g, equivalent to a body weight of 80 kg or a volume of 400 ml. The solution used for infusion is 20% mannitol in water for injection and is administered at a rate of 0.17 ml/kg/min.

Placebo Infusion (blinded)

Diagnostic Test

0.9% saline will be administered in the same amount as the mannitol dose infusion (= 5 ml/kg body weight), with a rate of 0.17 ml/kg/min in 30 minutes, with an upper limit of 400 ml (equivalent to a body weight of 80 kg).

Mannitol Infusion (open label)

Diagnostic Test

1.5 g of mannitol per kg body weight is infused in 30 minutes (≙ 7.5 ml/kg body weight), with an upper limit of 120 g, equivalent to a body weight of 80 kg or a volume of 600 ml. The solution used for infusion is 20% mannitol in water for injection.

Primary outcomes

  1. Difference in copeptin levels

    Time frame: Part 1: At 90 min post infusion, Part 2: at 30 min post infusion

    The difference in copeptin levels at 90 minutes following a 30-minute infusion of mannitol, part 1: compared to placebo in healthy adults and part 2: between patients with (primary polydipsia) PP and arginine vasopressin deficiency (AVP-D)

Secondary outcomes

  1. Change of copeptin levels

    Time frame: Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes

    Changes in copeptin levels compared to baseline.

  2. Maximum copeptin levels

    Time frame: Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes

    The maximum copeptin level after infusion is determined.

  3. Assessment of hormone level

    Time frame: Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes

    To determine the change in hormone levels, an assessment of hormones (e.g. Adrenocorticotropic hormone, Growth hormone, Insulin-like growth factor 1) is performed.

  4. Assessment of serum electrolytes

    Time frame: Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes

    To determine the change in electrolytes, an assessment of electrolytes (e.g. sodium potassium, chloride) in the serum is performed.

  5. Assessment of plasma osmolality

    Time frame: Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes

    To determine the change in parameters associated with fluid balance/ kidney function, an assessment of plasma osmolality (mOsm/kg) is performed.

  6. Assessment of urea

    Time frame: Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes

    To determine the change in parameters associated with fluid balance/ kidney function, an assessment of ureal levels (mmol/L) is performed.

  7. Assessment of uric acid

    Time frame: Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes

    To determine the change in parameters associated with fluid balance/ kidney function, an assessment of uric acid levels (umol/L) is performed.

  8. Assessment of creatinine

    Time frame: Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes

    To determine the change in parameters associated with fluid balance/ kidney function, an assessment of creatinine levels (umol/L) is performed.

  9. Assessment of glucose

    Time frame: Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes

    To determine the change in parameters associated with fluid balance/ kidney function, an assessment of glucose levels (mmol/L) is performed.

  10. Assessment of urine parameters

    Time frame: Part 1: At baseline, 90 and 150 min after infusion, Part 2: At baseline, 30 and 90 min after infusion

    To determine the change in urine parameters, an assessment of parameters (e.g. sodium, osmolality, creatinine) in the urine is performed.

  11. Assessment of blood pressure

    Time frame: Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes

    To determine the change of vital parameters, the blood pressure (systolic and diastolic) is assessed.

  12. Assessment of heart rate

    Time frame: Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes

    To determine the change of vital parameters, the heart rate is assessed.

  13. Assessment of adverse effects

    Time frame: Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes

    The incidence of adverse effects, such as nausea, headache, fatigue, dizziness, thirst, is assessed using the numeric rating scale from 0 to 10, where 0 represents "no pain" and 10 represents "the worst possible pain."

  14. Diagnostic accuracy of copeptin after mannitol Infusion for differentiating AVP-D from PP

    Time frame: Part 2: At 30 min post infusion

    Assessment of the diagnostic accuracy of stimulated copeptin levels measured after mannitol infusion to distinguish patients AVP-D from those with PP. The outcome will compare post-infusion copeptin concentrations between the two groups.

  15. Assessment of changes in ECG QTc Interval

    Time frame: Part 2: at Baseline and 90 min after infusion

    Assessment of the change in the corrected QT (QTc) interval on a standard ECG

  16. Assessment of changes in ECG Heart rate

    Time frame: Part 2: at Baseline and 90 min after infusion

    Assessment of the change in Heart rate on a standard ECG

  17. Assessment of changes in ECG Cardiac rhythm

    Time frame: Part 2: at Baseline and 90 min after infusion

    Assessment of the change in Cardiac rhythm on a standard ECG

  18. Assessment of changes in ECG QRS morphology

    Time frame: Part 2: at Baseline and 90 min after infusion

    Assessment of the change in QRS morphology on a standard ECG

  19. Assessment of changes in ECG P- and T wave morphology

    Time frame: Part 2: at Baseline and 90 min after infusion

    Assessment of the change in P- and T wave morphology on a standard ECG

Sponsors and collaborators

Lead sponsor

University Hospital, Basel, Switzerland

Other

Registry information

Official study title

Mannitol-induced Release of Copeptin in Healthy Adults and Patients With Polyuria-Polydipsia Syndrome: a Double-blind, Randomized Crossover Proof-of-concept and Open-label Single Arm Pilot Study (MARS Study)

Acronym: MARS

Important dates

Study start
2024
Primary completion
2025
Study completion
2025
First posted
Aug 7, 2024
Registry last updated
Dec 15, 2025

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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