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

NCT ID: NCT06542198

Last Updated: 2025-12-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

42 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-09-10

Study Completion Date

2025-07-22

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Polyuria-polydipsia Syndrome Arginine Vasopressin Deficiency Primary Polydipsia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

The study is conducted in two parts. Part 1: Cross-over proof-of-concept study Part 2: Single arm case-control pilot study
Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

The study is conducted in two parts. Part 1: Double-blind Part 2: Open-label

Study Groups

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Healthy adults

Part 1 of the study is conducted with healthy adults.

Group Type EXPERIMENTAL

Mannitol Infusion (blinded)

Intervention Type 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)

Intervention Type 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).

Primary polydipsia (PP) patients

Part 2 of the study is conducted with PP patients.

Group Type EXPERIMENTAL

Mannitol Infusion (open label)

Intervention Type 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.

Arginine vasopressin deficiency (AVP-D) patients

Part 2 of the study is conducted with AVP-D patients.

Group Type EXPERIMENTAL

Mannitol Infusion (open label)

Intervention Type 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.

Interventions

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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.

Intervention Type DIAGNOSTIC_TEST

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).

Intervention Type DIAGNOSTIC_TEST

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.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University Hospital, Basel, Switzerland

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mirjam Christ-Crain, Prof. Dr. med.

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Basel, Switzerland

Locations

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University Hospital Basel

Basel, , Switzerland

Site Status

Countries

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Switzerland

Other Identifiers

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2024-01214; kt24ChristCrain

Identifier Type: -

Identifier Source: org_study_id

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