Polyuria-polydipsia SyndromeMARSNCT06542198
Mannitol-induced Release of Copeptin in Healthy Adults and Patients With Polyuria-Polydipsia Syndrome (MARS Study)
A study testing Mannitol Infusion (blinded) and Mannitol Infusion (open label) in people with Polyuria-polydipsia Syndrome and Arginine Vasopressin Deficiency, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Polyuria-polydipsia Syndrome, Arginine Vasopressin Deficiency, Primary Polydipsia
- What is being tested?
- Mannitol Infusion (blinded) and Mannitol Infusion (open label)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 1 siteSwitzerland
- Study dates
- 10 Sep 2024to 22 Jul 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 20Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official 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)
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).
Read the detailed description
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.
- Being tested
- Mannitol Infusion (blinded), Placebo Infusion (blinded), Mannitol Infusion (open label)
- Keywords
- Hypertonic saline infusion, Mannitol, Copeptin
- 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.
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.
| Study group | Role | What they receive |
|---|---|---|
| Healthy adults | Experimental | Part 1 of the study is conducted with healthy adults. Receives: Diagnostic Test: Mannitol Infusion (blinded); Diagnostic Test: Placebo Infusion (blinded) |
| Primary polydipsia (PP) patients | Experimental | Part 2 of the study is conducted with PP patients. Receives: Diagnostic Test: Mannitol Infusion (open label) |
| Arginine vasopressin deficiency (AVP-D) patients | Experimental | Part 2 of the study is conducted with AVP-D patients. Receives: Diagnostic Test: Mannitol Infusion (open label) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in copeptin levels
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)
Measured: Part 1: At 90 min post infusion, Part 2: at 30 min post infusion
Secondary outcomes (19)
Change of copeptin levels
Changes in copeptin levels compared to baseline.
Measured: Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes
Maximum copeptin levels
The maximum copeptin level after infusion is determined.
Measured: Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes
Assessment of hormone level
To determine the change in hormone levels, an assessment of hormones (e.g. Adrenocorticotropic hormone, Growth hormone, Insulin-like growth factor 1) is performed.
Measured: Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes
Assessment of serum electrolytes
To determine the change in electrolytes, an assessment of electrolytes (e.g. sodium potassium, chloride) in the serum is performed.
Measured: Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes
Assessment of plasma osmolality
To determine the change in parameters associated with fluid balance/ kidney function, an assessment of plasma osmolality (mOsm/kg) is performed.
Measured: Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes
Assessment of urea
To determine the change in parameters associated with fluid balance/ kidney function, an assessment of ureal levels (mmol/L) is performed.
Measured: Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes
Assessment of uric acid
To determine the change in parameters associated with fluid balance/ kidney function, an assessment of uric acid levels (umol/L) is performed.
Measured: Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes
Assessment of creatinine
To determine the change in parameters associated with fluid balance/ kidney function, an assessment of creatinine levels (umol/L) is performed.
Measured: Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes
Assessment of glucose
To determine the change in parameters associated with fluid balance/ kidney function, an assessment of glucose levels (mmol/L) is performed.
Measured: Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes
Assessment of urine parameters
To determine the change in urine parameters, an assessment of parameters (e.g. sodium, osmolality, creatinine) in the urine is performed.
Measured: Part 1: At baseline, 90 and 150 min after infusion, Part 2: At baseline, 30 and 90 min after infusion
Assessment of blood pressure
To determine the change of vital parameters, the blood pressure (systolic and diastolic) is assessed.
Measured: Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes
Assessment of heart rate
To determine the change of vital parameters, the heart rate is assessed.
Measured: Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes
Assessment of adverse effects
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."
Measured: Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes
Diagnostic accuracy of copeptin after mannitol Infusion for differentiating AVP-D from PP
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.
Measured: Part 2: At 30 min post infusion
Assessment of changes in ECG QTc Interval
Assessment of the change in the corrected QT (QTc) interval on a standard ECG
Measured: Part 2: at Baseline and 90 min after infusion
Assessment of changes in ECG Heart rate
Assessment of the change in Heart rate on a standard ECG
Measured: Part 2: at Baseline and 90 min after infusion
Assessment of changes in ECG Cardiac rhythm
Assessment of the change in Cardiac rhythm on a standard ECG
Measured: Part 2: at Baseline and 90 min after infusion
Assessment of changes in ECG QRS morphology
Assessment of the change in QRS morphology on a standard ECG
Measured: Part 2: at Baseline and 90 min after infusion
Assessment of changes in ECG P- and T wave morphology
Assessment of the change in P- and T wave morphology on a standard ECG
Measured: Part 2: at Baseline and 90 min after infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2024
- Study start10 Sep 2024
- Primary completion22 Jul 2025
- Study completion22 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Polyuria-polydipsia SyndromeStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- The study is conducted in two parts. Part 1: Cross-over proof-of-concept study Part 2: Single arm case-control pilot study
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mirjam Christ-Crain, Prof. Dr. med., Principal investigator, University Hospital, Basel, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06542198
- Sponsor's protocol ID
- 2024-01214; kt24ChristCrain
- Acronym
- MARS
- Status last verified
- Dec 2025
- First submitted
- 26 Jul 2024
- Last updated
- 15 Dec 2025
- 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 15 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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)
- ClinicalTrials.gov ID
- NCT06542198
- Acronym / sponsor ID
- MARS / 2024-01214; kt24ChristCrain
- Keywords
- Hypertonic saline infusion, Mannitol, Copeptin
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- 10 Sep 2024 (actual)
- Primary completion
- 22 Jul 2025 (actual)
- Study completion
- 22 Jul 2025 (actual)
- First posted
- 7 Aug 2024 (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 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).
Detailed description
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- The study is conducted in two parts. Part 1: Cross-over proof-of-concept study Part 2: Single arm case-control pilot study
| Arm | Type | Receives |
|---|---|---|
| Healthy adults | Experimental | Diagnostic Test: Mannitol Infusion (blinded), Diagnostic Test: Placebo Infusion (blinded)Part 1 of the study is conducted with healthy adults. |
| Primary polydipsia (PP) patients | Experimental | Diagnostic Test: Mannitol Infusion (open label)Part 2 of the study is conducted with PP patients. |
| Arginine vasopressin deficiency (AVP-D) patients | Experimental | Diagnostic Test: Mannitol Infusion (open label)Part 2 of the study is conducted with AVP-D patients. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (20 listed)
- 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
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 |
|---|---|---|
| Mannitol Infusion (blinded)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. | Diagnostic test | Healthy adults |
| Placebo Infusion (blinded)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). | Diagnostic test | Healthy adults |
| Mannitol Infusion (open label)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. | Diagnostic test | Arginine vasopressin deficiency (AVP-D) patients, Primary polydipsia (PP) patients |
Primary outcome
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)
19 secondary outcomes
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
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
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
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
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
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
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
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
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
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
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
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
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
Diagnostic accuracy of copeptin after mannitol Infusion for differentiating AVP-D from PP
Time frame: Part 2: At 30 min post infusion
Assessment of changes in ECG QTc Interval
Time frame: Part 2: at Baseline and 90 min after infusion
Assessment of changes in ECG Heart rate
Time frame: Part 2: at Baseline and 90 min after infusion
Assessment of changes in ECG Cardiac rhythm
Time frame: Part 2: at Baseline and 90 min after infusion
Assessment of changes in ECG QRS morphology
Time frame: Part 2: at Baseline and 90 min after infusion
Assessment of changes in ECG P- and T wave morphology
Time frame: Part 2: at Baseline and 90 min after infusion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2025.
Related trials for Polyuria-polydipsia Syndrome
Recruiting
Copeptin Measurement After Mannitol and Hypertonic Saline for the Diagnosis of Polyuria-polydipsia Syndrome
Arginine Vasopressin Deficiency, Primary Polydipsia
Not yet recruiting
Arginin-stimulated Copeptin in Polyuria-polydipsia Syndrome in Children
Primary Polydipsia, Central Diabetes Insipidus
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. This study is not recruiting at the moment.
Mirjam Christ-Crain, Prof. Dr. med. principal investigator
University Hospital, Basel, Switzerland
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 Infusion (blinded) and Mannitol Infusion (open label) in people with Polyuria-polydipsia Syndrome and Arginine Vasopressin Deficiency, 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 6 inclusion and 20 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: finished, as of the sponsor's last update on 15 Dec 2025. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in copeptin levels (time frame: Part 1: At 90 min post infusion, Part 2: at 30 min post infusion). 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 15 Dec 2025.