Clinical trial NCT03572166: Use of Copeptin Measurement After Arginine Infusion for the Differential Diagnosis of Diabetes Insipidus - the CARGOx Study
Official title: Use of Copeptin Measurement After Arginine Infusion for the Differential Diagnosis of Diabetes Insipidus - the CARGOx Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Insipidus
Polydipsia, Primary
Keywords: Copeptin
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: University Hospital, Zürich
name: Wuerzburg University Hospital
name: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
name: Erasmus Medical Center
name: Cambridge University Hospitals NHS Foundation Trust
name: Federal University of Minas Gerais
First posted: 2018-06-28
Enrollment: 177
Sex: ALL
Minimum age (years): 18
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Observational randomized cross-over diagnostic international multicenter study
Primary purpose: DIAGNOSTIC

Brief summary: The differential diagnosis of central diabetes insipidus (cDI) is difficult and the current test with the highest diagnostic accuracy is copeptin measurement after hypertonic saline infusion (HIS). Although the HIS improved diagnostic accuracy compared to the standard water deprivation test used for decades before, it still comprises great discomfort for patients due to the rise in serum sodium levels above 149mmol/l and requires the presence of medical staff at all times to guarantee safety of the test.

The arginine stimulation test is routinely used to stimulate growth hormone. Own data in 52 patients with polyuria / polydipsia syndrome showed that arginine infusion is a potent stimulator of the neurohypophysis and provides a new diagnostic tool in the differential diagnosis of cDI. Copeptin measurements upon arginine stimulation (CAS) discriminated patients with diabetes insipidus vs. patients with primary polydipsia with a high diagnostic accuracy of 94%.

To validate these results and to compare them against the HIS a large multicenter trial is needed, where the diagnostic accuracy of the CAS is compared to the HIS.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Hypotonic polyuria / polydipsia syndrome defined as: polyuria \>50ml/kg body weight/24h and polydipsia \>3l /24h or known diabetes insipidus under treatment with DDAVP
* Urine-Osmolality \<800mOsm/L

Exclusion Criteria:

* Polyuria / polydipsia secondary to diabetes mellitus, hypercalcemia or hypokalemia
* Nephrogenic diabetes insipidus (defined as baseline copeptin level \>21.4pmol/L)
* Evidence of any acute illness
* Epilepsy requiring treatment
* Uncontrolled arterial hypertension (blood pressure \>160/100mmHg at baseline)
* Cardiac failure (NYHA III-IV)
* Liver cirrhosis (Child B-C)
* Uncorrected adrenal or thyroidal deficiency
* Patients refusing or unable to give written informed consent
* Pregnancy or breast feeding
* End of life care

Primary outcomes:
measure: The primary outcome is the overall diagnostic accuracy - defined as the proportion of correct diagnoses - of each diagnostic procedure in differentiating patients with central diabetes insipidus from patients with primary polydipsia.
timeFrame: 2 days
Secondary outcomes:
measure: Sensitivity of both diagnostic procedures for each diagnosis (Primary polydipsia, partial and complete central Diabetes insipidus) according to recommended diagnostic test criteria and previously generated cutoff values
timeFrame: 2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)
measure: Specificity of both diagnostic procedures for each diagnosis (Primary polydipsia, partial and complete central Diabetes insipidus) according to recommended diagnostic test criteria and previously generated cutoff values
timeFrame: 2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)
measure: Positive predictive value of both diagnostic procedures for each diagnosis (Primary polydipsia, partial and complete central Diabetes insipidus) according to recommended diagnostic test criteria and previously generated cutoff values
timeFrame: 2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)
measure: Negative predictive value of both diagnostic procedures for each diagnosis (Primary polydipsia, partial and complete central Diabetes insipidus) according to recommended diagnostic test criteria and previously generated cutoff values
timeFrame: 2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)
measure: Best fit diagnostic copeptin cut-off values for differentiation between each diagnosis (Primary polydipsia, partial and complete central Diabetes insipidus) upon arginine stimulation and hypertonic saline infusion stimulation
timeFrame: 2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)
measure: Accuracy of the copeptin cut-off of 3.7 pmol/l after 60 minutes and 4.1 after 90 minutes for Arginine Stimulation test
timeFrame: 2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)
measure: Sensitivity of the copeptin cut-off of 3.7 pmol/l after 60 minutes and 4.1 after 90 minutes for Arginine Stimulation test
timeFrame: 2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)
measure: Specificity of the copeptin cut-off of 3.7 pmol/l after 60 minutes and 4.1 after 90 minutes for Arginine Stimulation test
timeFrame: 2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)
measure: Accuracy of the copeptin cut-off of 6.5 pmol/l for Hypertonic Saline Infusion test
timeFrame: 2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)
measure: Sensitivity of the copeptin cut-off of 6.5 pmol/l for Hypertonic Saline Infusion test
timeFrame: 2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)
measure: Specificity of the copeptin cut-off of 6.5 pmol/l for Hypertonic Saline Infusion test
timeFrame: 2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)
measure: Frequency and severity of thirst assessed by visual analogue scale during both tests
timeFrame: 2 days (1 for each test)
measure: Frequency and severity of headache assessed by visual analogue scale during both tests
timeFrame: 2 days (1 for each test)
measure: Frequency and severity of nausea assessed by visual analogue scale during both tests
timeFrame: 2 days (1 for each test)
measure: Frequency and severity of vertigo assessed by visual analogue scale during both tests
timeFrame: 2 days (1 for each test)
measure: Frequency and severity of general malaise assessed by visual analogue scale during both tests
timeFrame: 2 days (1 for each test)
measure: Subjective burden assessed by visual analogue scale of both tests
timeFrame: 2 days (1 for each test)
measure: Health care costs of both tests
timeFrame: 2 days (1 for each test)
measure: Frequency of test preference at follow up visit
timeFrame: 30 days
Other outcomes:
Locations:
city: Belo Horizonte
country: Brazil
facility: Hospital das clinicas Minas Gerais
city: Würzburg
country: Germany
facility: University Hospital Würzburg
city: Milan
country: Italy
facility: Granda Ospedale Maggiore Policlinico Milan
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Basel
country: Switzerland
facility: University Hospital Basel, Department of Endocrinology
state: Basel Stadt
city: Zürich
country: Switzerland
facility: University Hospital Zurich
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospital
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Mirjam Christ-Crain, Prof, MD
role: PRINCIPAL_INVESTIGATOR
References: