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

NCT06542198 | Completed

• 1 other identifier: 2024-01214; kt24ChristCrain
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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).

Conditions

Polyuria-polydipsia Syndrome; Arginine Vasopressin Deficiency; Primary Polydipsia

Keywords

Hypertonic saline infusion; Mannitol; Copeptin

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (19)

• Change of copeptin levels

  Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes

• Maximum copeptin levels

  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

  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

  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

  Part 1: At baseline, 30, 45, 60, 90, and 150 min after infusion, Part 2: At baseline, 30 and 90 minutes

Study Arms (3)

Healthy adults

EXPERIMENTAL

Part 1 of the study is conducted with healthy adults.

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.

Diagnostic Test: Mannitol Infusion (open label)

Arginine vasopressin deficiency (AVP-D) patients

EXPERIMENTAL

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

Diagnostic Test: Mannitol Infusion (open label)

Interventions

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).

Healthy adults

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.

Arginine vasopressin deficiency (AVP-D) patients; Primary polydipsia (PP) patients

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.

Healthy adults

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Hospital Basel

Basel, 4031, Switzerland

Location

MeSH Terms

Conditions

Diabetes Insipidus, Neurogenic; Polydipsia, Psychogenic; Diabetes Insipidus

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pituitary Diseases; Endocrine System Diseases; Polydipsia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Behavioral Symptoms; Behavior

Study Officials

• Mirjam Christ-Crain, Prof. Dr. med.

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: The study is conducted in two parts. Part 1: Double-blind Part 2: Open-label
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: July 26, 2024
• First Posted: August 7, 2024
• Study Start: September 10, 2024
• Primary Completion: July 22, 2025
• Study Completion: July 22, 2025
• Last Updated: December 15, 2025

Record last verified: 2025-12

Locations

CH (1)