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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy adults | Experimental | Part 1 of the study is conducted with healthy adults. |
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| Primary polydipsia (PP) patients | Experimental | Part 2 of the study is conducted with PP patients. |
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| Arginine vasopressin deficiency (AVP-D) patients | Experimental | Part 2 of the study is conducted with AVP-D patients. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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) | Part 1: At 90 min post infusion, Part 2: at 30 min post infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Change of copeptin levels | Changes in copeptin levels compared to baseline. | Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes |
| Maximum copeptin levels |
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Inclusion Criteria:
Part 1: Proof of Concept in Healthy adults
Part 2: Pilot Study in Patients with primary polydipsia (PP) or arginine vasopressin deficiency (AVP-D)
Exclusion Criteria:
Part 1: Proof of Concept in Healthy adults
Part 2: Pilot Study in Patients with PP or AVP-D
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| Name | Affiliation | Role |
|---|---|---|
| Mirjam Christ-Crain, Prof. Dr. med. | University Hospital, Basel, Switzerland | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Basel | Basel | 4031 | Switzerland |
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The study is conducted in two parts. Part 1: Cross-over proof-of-concept study Part 2: Single arm case-control pilot study
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The study is conducted in two parts. Part 1: Double-blind Part 2: Open-label
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| 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). |
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| 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. |
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The maximum copeptin level after infusion is determined.
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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." | 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. | 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 | 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 | 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 | 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 | 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 | Part 2: at Baseline and 90 min after infusion |
| 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 |
| 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 |
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