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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03572166
Other study ID # CARGOx
Secondary ID
Status Completed
Phase N/A
First received
Last updated
Start date September 3, 2018
Est. completion date December 31, 2022

Study information

Verified date July 2023
Source University Hospital, Basel, Switzerland
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 177
Est. completion date December 31, 2022
Est. primary completion date September 30, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years to 95 Years
Eligibility 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

Study Design


Intervention

Diagnostic Test:
Arginine infusion
Intravenous Infusion of Arginine is given, copeptin measurement will be collected before and 60minutes after start of infusion
Hypertonic saline infusion
Intravenous Infusion of hypertonic Saline is given, copeptin measurement will be collected before and once Plasma sodium rises above 149mmol/l

Locations

Country Name City State
Brazil Hospital das clinicas Minas Gerais Belo Horizonte
Germany University Hospital Würzburg Würzburg
Italy Granda Ospedale Maggiore Policlinico Milan Milan
Netherlands Erasmus MC Rotterdam
Switzerland University Hospital Basel, Department of Endocrinology Basel Basel Stadt
Switzerland University Hospital Zurich Zürich
United Kingdom Cambridge University Hospital Cambridge

Sponsors (7)

Lead Sponsor Collaborator
University Hospital, Basel, Switzerland Cambridge University Hospitals NHS Foundation Trust, Erasmus Medical Center, Federal University of Minas Gerais, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, University Hospital, Zürich, Wuerzburg University Hospital

Countries where clinical trial is conducted

Brazil,  Germany,  Italy,  Netherlands,  Switzerland,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. For Arginine stimulation the copeptin cut-off to differentiate between diabetes insipidus and primary polydipsia will be 3.8 pmol/l after 60 minutes, for hypertonic saline stimulation it will be the copeptin cut-off 4.9 pmol/l taken at the end of the test 2 days
Secondary 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 Copeptin cut-offs used:
Arginine stimulation:
Copeptin level at 60 minutes < 2.4 pmol/l = complete central diabetes insipidus
Copeptin level at 60 minutes 2.4 - 3.8 pmol/l = partial central diabetes insipidus
Copeptin level at 60 minutes > 3.8 pmol/l = primary polydipsia
Hypertonic saline stimulation:
Copeptin level < 2.7 pmol/l = complete central diabetes insipidus
Copeptin level 2.7 - 4.9 pmol/l = partial central diabetes insipidus
Copeptin level > 4.9 pmol/l = primary polydipsia
2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)
Secondary 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 Copeptin cut-offs used:
Arginine stimulation:
Copeptin level at 60 minutes < 2.4 pmol/l = complete central diabetes insipidus
Copeptin level at 60 minutes 2.4 - 3.8 pmol/l = partial central diabetes insipidus
Copeptin level at 60 minutes > 3.8 pmol/l = primary polydipsia
Hypertonic saline stimulation:
Copeptin level < 2.7 pmol/l = complete central diabetes insipidus
Copeptin level 2.7 - 4.9 pmol/l = partial central diabetes insipidus
Copeptin level > 4.9 pmol/l = primary polydipsia
2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)
Secondary 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 Copeptin cut-offs used:
Arginine stimulation:
Copeptin level at 60 minutes < 2.4 pmol/l = complete central diabetes insipidus
Copeptin level at 60 minutes 2.4 - 3.8 pmol/l = partial central diabetes insipidus
Copeptin level at 60 minutes > 3.8 pmol/l = primary polydipsia
Hypertonic saline stimulation:
Copeptin level < 2.7 pmol/l = complete central diabetes insipidus
Copeptin level 2.7 - 4.9 pmol/l = partial central diabetes insipidus
Copeptin level > 4.9 pmol/l = primary polydipsia
2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)
Secondary 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 Copeptin cut-offs used:
Arginine stimulation:
Copeptin level at 60 minutes < 2.4 pmol/l = complete central diabetes insipidus
Copeptin level at 60 minutes 2.4 - 3.8 pmol/l = partial central diabetes insipidus
Copeptin level at 60 minutes > 3.8 pmol/l = primary polydipsia
Hypertonic saline stimulation:
Copeptin level < 2.7 pmol/l = complete central diabetes insipidus
Copeptin level 2.7 - 4.9 pmol/l = partial central diabetes insipidus
Copeptin level > 4.9 pmol/l = primary polydipsia
2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)
Secondary 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 2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)
Secondary Accuracy of the copeptin cut-off of 3.7 pmol/l after 60 minutes and 4.1 after 90 minutes for Arginine Stimulation test 2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)
Secondary Sensitivity of the copeptin cut-off of 3.7 pmol/l after 60 minutes and 4.1 after 90 minutes for Arginine Stimulation test 2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)
Secondary Specificity of the copeptin cut-off of 3.7 pmol/l after 60 minutes and 4.1 after 90 minutes for Arginine Stimulation test 2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)
Secondary Accuracy of the copeptin cut-off of 6.5 pmol/l for Hypertonic Saline Infusion test 2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)
Secondary Sensitivity of the copeptin cut-off of 6.5 pmol/l for Hypertonic Saline Infusion test 2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)
Secondary Specificity of the copeptin cut-off of 6.5 pmol/l for Hypertonic Saline Infusion test 2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)
Secondary Frequency and severity of thirst assessed by visual analogue scale during both tests assessed by visual analogue scale from 0 to 10, with 0 indicating no symptoms and 10 indicating severe symptoms. 2 days (1 for each test)
Secondary Frequency and severity of headache assessed by visual analogue scale during both tests assessed by visual analogue scale from 0 to 10, with 0 indicating no symptoms and 10 indicating severe symptoms. 2 days (1 for each test)
Secondary Frequency and severity of nausea assessed by visual analogue scale during both tests assessed by visual analogue scale from 0 to 10, with 0 indicating no symptoms and 10 indicating severe symptoms. 2 days (1 for each test)
Secondary Frequency and severity of vertigo assessed by visual analogue scale during both tests assessed by visual analogue scale from 0 to 10, with 0 indicating no symptoms and 10 indicating severe symptoms. 2 days (1 for each test)
Secondary Frequency and severity of general malaise assessed by visual analogue scale during both tests assessed by visual analogue scale from 0 to 10, with 0 indicating no symptoms and 10 indicating severe symptoms. 2 days (1 for each test)
Secondary Subjective burden assessed by visual analogue scale of both tests assessed by visual analogue scale from 0 to 10, with 0 indicating no symptoms and 10 indicating severe symptoms. 2 days (1 for each test)
Secondary Health care costs of both tests 2 days (1 for each test)
Secondary Frequency of test preference at follow up visit 30 days
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