Arginin-stimulated Copeptin in Polyuria-polydipsia Syndrome in Children

NCT06604975 | Not Yet Recruiting

• 1 other identifier: RCAPHM23_0379
• Study Type: interventional
• Target: 155
• Locations: 1 country
• Sites: 14

Brief Summary

The exploration of polyuro-polydipsia syndrome (PPS) with hypotonic polyuria should distinguished, primary polydipsia (PP) due to excessive water intake, central diabetes insipidus (CDI) related to insufficient secretion of antidiuretic hormone (AVP), and nephrogenic diabetes insipidus (NDI) related to AVP insensitivity. The determination of plasma AVP is not relevant (unstable concentration, short in vitro half-life, long technical time and large blood sample). The differential diagnosis is currently based on a water deprivation test (WDT), an indirect reflection of AVP action, requiring more than 6 hours of hospitalization with risk of dehydration and low accuracy. Copeptin represents a new biomarker, direct mirror of AVP release with remarkable characteristics (stable, rapid determination, small blood volume). Copeptin has become a diagnostic tool in adult PPS and eliminated WDT in the diagnostic process. In children, basal copeptin values help for NDI and to exclude CDI (basal copeptin threshold \> 30 and \> 3.53 pmol/l (Se 100%, Sp 87.4%), respectively). Below 3.53 pmol/l, basal copeptin performance was inadequate to discriminate PP and CDI, highlighting the relevance of the stimulated copeptin study to improve this strategy. The arginine stimulation test is widely used as a simple, short duration (2 hours) and well tolerated tool to diagnose growth hormone deficiency in pediatrics. The performance of this test for copeptin stimulation was studied in adults with PPS with a high diagnostic accuracy. The aim of the study is identify the best discriminant threshold of the arginine stimulation test in the uncertain diagnosis (basal copeptin \<30 pmol/l) in the polyuro-polydipsic syndrome in children. Then evaluate the discriminative capacities of the arginine stimulation test between the primary polydipsia and central insipid diabetes in the polyuro-polydipsic syndrome in children. And finally evaluate the cost-effectiveness of a new decisional algorithm for the differential diagnosis of PPS in children and evaluate the impact of infusion volume on copeptin secretion using the protidemia copeptin ratio.

Conditions

Primary Polydipsia; Central Diabetes Insipidus; Nephrogenic Diabetes Insipidus

Outcome Measures

Primary Outcomes (1)

• Measurement of arginine-stimulated copeptine level

  Determine arginine-stimulated copeptine level for each time (T45min, T60min, T90min, T120min)

  Different time points of argenine stimulates copeptine level will be measured at 45 minutes, 60 minutes, 90 minutes and 120 minutes

Secondary Outcomes (2)

• Cost savings applying a new algorithm for the exploration of the Polyuria-polydipsia Syndrome using an Argenin-stimulated copeptin test

  Month 36

• Copeptin Ratio

  Month 36

Study Arms (1)

NDI-PP- CDI groups

EXPERIMENTAL

Copeptin represents a new biomarker, direct mirror of AVP release with remarkable characteristics (stable, rapid determination, small blood volume). Copeptin has become a diagnostic tool in adult PPS and eliminated WDT in the diagnostic process. In children, basal copeptin values help for NDI and to exclude CDI (basal copeptin threshold \> 30 and \>3.53 pmol/l (Se 100%, Sp 87.4%), respectively). Below 3.53 pmol/l, basal copeptin performance was inadequate to discriminate PP and CDI, highlighting the relevance of the stimulated copeptin study to improve this strategy.

Procedure: Measure of Basal Copeptin level; Procedure: Measure of arginine-stimulated copeptin; Procedure: IRM; Behavioral: Water reduction at home

Interventions

Measure of Basal Copeptin level PROCEDURE

Copeptin test is performed after solid fasting since midnight without water restriction. After blood collection on heparin tube used for biological inclusion criteria, heparinized plasma is transferred to Timone University hospital (transport temperature +4°C) for screening copeptin assay. The basal copeptin level determines the next step: 1. copeptin ≥ 30 pmol/L defines the diagnosis of NDI and results in a specific care; 2. copeptin \&lt; 30 pmol/L defines the group of eligible patients for arginine stimulation

NDI-PP- CDI groups

Measure of arginine-stimulated copeptin PROCEDURE

The arginine-stimulated copeptin test start at 8 am, after solid fasting since midnight without water restriction, and 30 min of rest in decubitus position. A dose of 0.5 g/kg of arginine (maximum 40g) diluted in 0.9% NaCl is infused over 30 min through a peripheral venous line. Copeptin is measured at T0 (before infusion), T45, T60, T90, and T120 min after infusion.

NDI-PP- CDI groups

IRM PROCEDURE

Based on our previous study, patients with basal copeptin value over 3.53 pmol/L are considered as positive diagnosis of PP (Se 100%, Sp 87.4%) and cerebral MRI is not performed for this group of patients (PP group). A cerebral and pituitary MRI performed according to reference procedures (without and with contrast medium used in routine care) for patients considered as an uncertain diagnosis (UD) based on basal copeptin value (\&amp;lt; 3.53 pmol/L). MRI interpretation is performed by two independent neuroradiologists (one from the recruiting center and one from the pilot center). In case of discrepancies, a third independent interpretation will be performed by a neuroradiologist from the coordinating center. Abnormal pituitary MRI (thickened pituitary stalk pituitary tumor, ectopic neurohypophysis, septo-optic dysplasia, empty sellar, Rathke pouch) allows a diagnosis of CDI leading to etiological investigations and AVP treatment.

NDI-PP- CDI groups

Water reduction at home BEHAVIORAL

Patients with basal copeptin ≥ 3.53 pmol/l (PP group), and UD patients with normal MRI have gradual reduction of water intake at home without AVP treatment : gradual reduction with 20% in the first week, 30% in the second, 40% in the third, reaching 50% of daily fluid in the last week including restriction overnight, deletion drink before sleep. Some recommendations will be provided to help physicians. For all these latest patients, a clinical reassessment (weight, height, heart rate, blood pressure, input/output 24 hours balance) is performed one month later.

NDI-PP- CDI groups

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Children aged 2 to 18 years with polyuro-polydipsia syndrome (defined as hypotonic diuresis \&gt; 50 mL/kg/day in pediatric age or 30 mL/kg/day in late puberty (Tanner 5)) presenting for differential diagnosis between PP and DIC
• Basal copeptin of less than 30 pmol/l
• Agreeing to participate in the study
• Whose two parents' consent to have their child participate in the study.

You may not qualify if:

• Diabetes mellitus
• Unbalanced dysthyroidism
• Corticotropic deficiency
• Ionic disorders (dysnatremia \&lt; 135 or \&gt; 145 mmol/l, dyskalemia \&lt; 3 or \&gt; 5 mmol/l, corrected dyscalcemia \&lt; 2.2 or \&gt; 2.6 mmol/L)
• Moderate to severe clinical dehydration (recent weight loss \&gt; 5% of body weight, clinical or biological signs of dehydration) requiring immediate therapeutic management
• Renal failure with GFR \&lt; 60 mL/min/1.73 m2
• Uropathy
• Tumor syndrome (except hypothalamo-pituitary tumor)
• Intracranial hypertension
• ROHHAD syndrome
• Fever or biological inflammatory syndrome with CRP \&gt; 5 mg/L
• Hepatic insufficiency
• Contraindication to MRI
• Contraindication to progressive water intake restrictions
• History of contraindication to arginine

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead

Study Sites (14)

CHU Angers

Angers, France

Location

CHU de Bordeaux

Bordeaux, France

Location

CHU Lille

Lille, France

Location

HCL

Lyon, France

Location

Assistance Publique Hopitaux de Marseille

Marseille, France

Location

CHU Montpellier

Montpellier, France

Location

CHU Nantes

Nantes, France

Location

CHU Nice

Nice, France

Location

AP-HP

Paris, France

Location

CH Pau

Pau, France

Location

CHU Reims

Reims, France

Location

CHU Rennes

Rennes, France

Location

CHU Rouen

Rouen, France

Location

CHU Toulouse

Toulouse, France

Location

MeSH Terms

Conditions

Polydipsia, Psychogenic; Diabetes Insipidus, Neurogenic; Diabetes Insipidus, Nephrogenic

Condition Hierarchy (Ancestors)

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

Study Officials

• Rachel REYNAUD, Pr

  AP-HM

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rachel REYNAUD

CONTACT

0491388040; Rachel.REYNAUD@ap-hm.fr

Rawand MASOUD

CONTACT

rawand.masoud@ap-hm.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2024
• First Posted: September 20, 2024
• Study Start: March 1, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: February 13, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (14)