Plasma Copeptin in Response to Oral Urea in Healthy Adults and Patients With Polyuria-polydipsia Syndrome (URANOS)

Plasma Copeptin in Response to Oral Urea in Healthy Adults and Patients With Polyuria-polydipsia Syndrome: a Double-blind, Randomized, Placebo-controlled Cross-over Proof-of-concept and Pilot Study - The URANOS Study

The aim of this study is to investigate whether oral urea stimulates copeptin release and, if so, whether it may provide a novel diagnostic test in the differentiation between AVP-D (Arginine vasopressin deficiency) and PP (primary polydipsia).

Study Overview

• Status: Completed
• Conditions: Primary Polydipsia; Arginine Vasopressin Deficiency
• Intervention / Treatment: Diagnostic test: Urea; Diagnostic test: Placebo

Detailed Description

This study consists of two parts, including healthy adults (study part 1 - proof of concept) and adults with an established diagnosis of PP or AVP-D (study part 2 - pilot study).

If the results of study part 1 suggest that oral urea is a potent stimulator of copeptin in healthy adults, study part 2 will be conducted, meaning that adults with an established diagnosis of PP or AVP-D will be included. If study part 1 demonstrates no relevant copeptin increase in response to oral urea, the study will be terminated thereafter and study part 2 will not be conducted.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Healthy volunteers

Inclusion Criteria:

• Age ≥18 years
• Healthy with no medication except hormonal contraception

Exclusion Criteria:

• Participation in a trial with investigational drugs within 30 days
• Evidence of disordered drinking habits and diuresis defined as polyuria >50ml/kg body weight/24h and polydipsia >3l /24h
• Known allergy towards components of the study drink
• Pregnancy and breastfeeding
• Intention to become pregnant during the study
• Evidence of acute illness

Patients

Inclusion Criteria:

• Age ≥ 18 years
• Documented PP or AVP-D based on accepted diagnostic criteria, i.e., water deprivation test, hypertonic saline infusion test or arginine infusion test. Accordingly, patients must have evidence of disordered drinking habits and diuresis defined as polyuria >50ml/kg body weight/24h and polydipsia >3l /24h or must be on regular daily desmopressin medication

Exclusion Criteria:

• Participation in a trial with investigational drugs within 30 days
• Known allergy towards components of the study drink
• Pregnancy and breastfeeding
• Evidence of acute illness

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study Part 1 urea followed by placebo; Participants will undergo a diagnostic test with a single weight-adapted dose of oral urea first. After a a wash-out phase of at least 3 days and not more than 28 days participants will undergo a second diagnostic test with a single weight-adapted dose of placebo.	Diagnostic test: Urea; Diagnostic test with a single weight-adapted dose of oral urea dissolved in 200 ml water together with 5 g of lemon-lime flavor powder (containing maltodextrin and citric acid). The investigators will make use of the lemon-lime flavor to soften the bitter taste of urea. - Dose calculation: 0.5 g urea/kg body weight (rounded to no decimal places), with a minimal dose of 30g and a maximal dose of 45g.; Diagnostic test: Placebo; Diagnostic test with a single weight-adapted dose of placebo dissolved in 200 ml water together with 5 g of lemon-lime flavor powder (containing maltodextrin and citric acid). The placebo will contain a mixture of bitter herbal substances to mimic the taste of urea. - Dose calculation: 22 ml of placebo containing 20 ml Ergytonyl®, 1 ml Carmol®, and 1 ml Bitter Liebe®.
Experimental: Study Part 1 placebo followed by urea; Participants will undergo a diagnostic test with a single weight-adapted dose of placebo first. After a a wash-out phase of at least 3 days and not more than 28 days participants will undergo a second diagnostic test with a single weight-adapted dose of urea.	Diagnostic test: Urea; Diagnostic test with a single weight-adapted dose of oral urea dissolved in 200 ml water together with 5 g of lemon-lime flavor powder (containing maltodextrin and citric acid). The investigators will make use of the lemon-lime flavor to soften the bitter taste of urea. - Dose calculation: 0.5 g urea/kg body weight (rounded to no decimal places), with a minimal dose of 30g and a maximal dose of 45g.; Diagnostic test: Placebo; Diagnostic test with a single weight-adapted dose of placebo dissolved in 200 ml water together with 5 g of lemon-lime flavor powder (containing maltodextrin and citric acid). The placebo will contain a mixture of bitter herbal substances to mimic the taste of urea. - Dose calculation: 22 ml of placebo containing 20 ml Ergytonyl®, 1 ml Carmol®, and 1 ml Bitter Liebe®.
Experimental: Study part 2 Urea; Participants will undergo a diagnostic test with a single weight-adapted dose of oral urea	Diagnostic test: Urea; Diagnostic test with a single weight-adapted dose of oral urea dissolved in 200 ml water together with 5 g of lemon-lime flavor powder (containing maltodextrin and citric acid). The investigators will make use of the lemon-lime flavor to soften the bitter taste of urea. - Dose calculation: 0.5 g urea/kg body weight (rounded to no decimal places), with a minimal dose of 30g and a maximal dose of 45g.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in maximal increase in copeptin levels in plasma (pmol/l)	The difference in maximal increase in copeptin levels in plasma (pmol/l) within 150 minutes after oral intake of urea versus placebo, with the maximal increase being the difference between baseline copeptin values measured at the beginning of the test and maximal values measured between 30 and 150 minutes after ingestion.	up to 6 time assessment until 150 minutes after baseline

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Mirjam Christ-Crain, Prof., University Hospital, Basel, Switzerland

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2023
• Primary Completion (Actual): June 24, 2024
• Study Completion (Actual): June 24, 2024

Study Registration Dates

• First Submitted: May 23, 2023
• First Submitted That Met QC Criteria: June 5, 2023
• First Posted (Actual): June 6, 2023

Study Record Updates

• Last Update Posted (Actual): July 9, 2024
• Last Update Submitted That Met QC Criteria: July 8, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: copeptin; diabetes insipidus; oral urea
• Additional Relevant MeSH Terms: Behavioral Symptoms; Pathologic Processes; Kidney Diseases; Urologic Diseases; Urological Manifestations; Neurobehavioral Manifestations; Endocrine System Diseases; Urination Disorders; Pituitary Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Polyuria; Diabetes Insipidus; Polydipsia; Diabetes Insipidus, Neurogenic; Polydipsia, Psychogenic
• Other Study ID Numbers: 2023-00751; kt23christcrain2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No