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

Not Applicable

Recruiting

• Conditions: Polyuria-polydipsia Syndrome; Primary Polydipsia; Arginine Vasopressin Deficiency

• Registration Number: NCT06542198
• Lead Sponsor: University Hospital, Basel, Switzerland

Brief 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).

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 Timeline

• Study First Submitted: 2024-07-26
• Study First Submitted QC: 2024-08-02
• Study First Posted: 2024-08-07
• Study Start: 2024-09-10
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-06
• Last Update Posted: 2024-12-12
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 42

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Difference in copeptin levels	At 90 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 Outcome Measures

Name	Time	Method
Maximum copeptin levels	At baseline, 30, 45, 60, 90, and 150 min after infusion	The maximum copeptin level after infusion is determined.
Assessment of creatinine	At baseline, 90, and 150 min after infusion	To determine the change in parameters associated with fluid balance/ kidney function, an assessment of creatinine levels (umol/L) is performed.
Change of copeptin levels	At baseline, 30, 45, 60, 90, and 150 min after infusion	Changes in copeptin levels compared to baseline.
Assessment of hormone level	At baseline, 30, 45, 60, 90, and 150 min after infusion	To determine the change in hormone levels, an assessment of hormones (e.g. Adrenocorticotropic hormone, Growth hormone, Insulin-like growth factor 1) is performed.
Assessment of serum electrolytes	At baseline, 30, 45, 60, 90, and 150 min after infusion	To determine the change in electrolytes, an assessment of electrolytes (e.g. sodium potassium, chloride) in the serum is performed.
Assessment of plasma osmolality	At baseline, 30, 45, 60, 90, and 150 min after infusion	To determine the change in parameters associated with fluid balance/ kidney function, an assessment of plasma osmolality (mOsm/kg) is performed.
Assessment of uric acid	At baseline, 30, 45, 60, 90, and 150 min after infusion	To determine the change in parameters associated with fluid balance/ kidney function, an assessment of uric acid levels (umol/L) is performed.
Assessment of heart rate	At baseline, 30, 45, 60, 90, and 150 min after infusion	To determine the change of vital parameters, the heart rate is assessed.
Assessment of urea	At baseline, 30, 45, 60, 90, and 150 min after infusion	To determine the change in parameters associated with fluid balance/ kidney function, an assessment of ureal levels (mmol/L) is performed.
Assessment of urine parameters	At baseline, 90 and 150 min after infusion	To determine the change in urine parameters, an assessment of parameters (e.g. sodium, osmolality, creatinine) in the urine is performed.
Assessment of blood pressure	At baseline, 30, 45, 60, 90, and 150 min after infusion	To determine the change of vital parameters, the blood pressure (systolic and diastolic) is assessed.
Assessment of adverse effects	At baseline, 30, 45, 60, 90, and 150 min after infusion	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."
Assessment of glucose	At baseline, 30, 45, 60, 90, and 150 min after infusion	To determine the change in parameters associated with fluid balance/ kidney function, an assessment of glucose levels (mmol/L) is performed.

Trial Locations

Locations (1)

University Hospital Basel; 🇨🇭 Basel, Switzerland