Clinical trial NCT06542198: Mannitol-induced Release of Copeptin in Healthy Adults and Patients With Polyuria-Polydipsia Syndrome (MARS 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Polyuria-polydipsia Syndrome
Arginine Vasopressin Deficiency
Primary Polydipsia
Keywords: Hypertonic saline infusion
Mannitol
Copeptin
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2024-08-07
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Difference in copeptin levels
timeFrame: At 90 min post infusion
Secondary outcomes:
measure: Change of copeptin levels
timeFrame: At baseline, 30, 45, 60, 90, and 150 min after infusion
measure: Maximum copeptin levels
timeFrame: At baseline, 30, 45, 60, 90, and 150 min after infusion
measure: Assessment of hormone level
timeFrame: At baseline, 30, 45, 60, 90, and 150 min after infusion
measure: Assessment of serum electrolytes
timeFrame: At baseline, 30, 45, 60, 90, and 150 min after infusion
measure: Assessment of plasma osmolality
timeFrame: At baseline, 30, 45, 60, 90, and 150 min after infusion
measure: Assessment of urea
timeFrame: At baseline, 30, 45, 60, 90, and 150 min after infusion
measure: Assessment of uric acid
timeFrame: At baseline, 30, 45, 60, 90, and 150 min after infusion
measure: Assessment of creatinine
timeFrame: At baseline, 90, and 150 min after infusion
measure: Assessment of glucose
timeFrame: At baseline, 30, 45, 60, 90, and 150 min after infusion
measure: Assessment of urine parameters
timeFrame: At baseline, 90 and 150 min after infusion
measure: Assessment of blood pressure
timeFrame: At baseline, 30, 45, 60, 90, and 150 min after infusion
measure: Assessment of heart rate
timeFrame: At baseline, 30, 45, 60, 90, and 150 min after infusion
measure: Assessment of adverse effects
timeFrame: At baseline, 30, 45, 60, 90, and 150 min after infusion
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Mirjam Christ-Crain, Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: