Use of Copeptin Measurement After Arginine Infusion for the Differential Diagnosis of Diabetes Insipidus - the CARGOx Study
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arginine Infusion Arginine Stimulation Test |
Diagnostic Test: Arginine infusion
Intravenous Infusion of Arginine is given, copeptin measurement will be collected before and 60minutes after start of infusion
|
| Active Comparator: Hypertonic saline infusion Hypertonic Saline Infusion Test |
Diagnostic Test: Hypertonic saline infusion
Intravenous Infusion of hypertonic Saline is given, copeptin measurement will be collected before and once Plasma sodium rises above 149mmol/l
|
Outcome Measures
Primary Outcome Measures
- 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. [2 days]
Secondary Outcome Measures
- 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 [2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)]
- 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 [2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)]
- 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 [2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)]
- 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 [2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)]
- 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)]
- Accuracy of the copeptin cut-off of 3.5pmol/l for Arginine Stimulation test [2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)]
- Sensitivity of the copeptin cut-off of 3.5pmol/l for Arginine Stimulation test [2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)]
- Specificity of the copeptin cut-off of 3.5pmol/l for Arginine Stimulation test [2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)]
- Accuracy of the copeptin cut-off of 6.5pmol/l for Hypertonic Saline Infusion test [2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)]
- Sensitivity of the copeptin cut-off of 6.5pmol/l for Hypertonic Saline Infusion test [2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)]
- Specificity of the copeptin cut-off of 6.5pmol/l for Hypertonic Saline Infusion test [2 days (1 day for each test, evaluation diagnostic accuracy at end of trial)]
- Frequency and severity of thirst assessed by visual analogue scale during both tests [2 days (1 for each test)]
assessed by visual analogue scale from 0 to 10, with 0 indicating no symptoms and 10 indicating severe symptoms.
- Frequency and severity of headache assessed by visual analogue scale during both tests [2 days (1 for each test)]
assessed by visual analogue scale from 0 to 10, with 0 indicating no symptoms and 10 indicating severe symptoms.
- Frequency and severity of nausea assessed by visual analogue scale during both tests [2 days (1 for each test)]
assessed by visual analogue scale from 0 to 10, with 0 indicating no symptoms and 10 indicating severe symptoms.
- Frequency and severity of vertigo assessed by visual analogue scale during both tests [2 days (1 for each test)]
assessed by visual analogue scale from 0 to 10, with 0 indicating no symptoms and 10 indicating severe symptoms.
- Frequency and severity of general malaise assessed by visual analogue scale during both tests [2 days (1 for each test)]
assessed by visual analogue scale from 0 to 10, with 0 indicating no symptoms and 10 indicating severe symptoms.
- Subjective burden assessed by visual analogue scale of both tests [2 days (1 for each test)]
assessed by visual analogue scale from 0 to 10, with 0 indicating no symptoms and 10 indicating severe symptoms.
- Health care costs of both tests [2 days (1 for each test)]
- Frequency of test preference at follow up visit [30 days]
Eligibility Criteria
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
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Urine-Osmolality <800mOsm/L
Exclusion Criteria:
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Polyuria / polydipsia secondary to diabetes mellitus, hypercalcemia or hypokalemia
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Nephrogenic diabetes insipidus (defined as baseline copeptin level >21.4pmol/L)
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Evidence of any acute illness
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Epilepsy requiring treatment
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Uncontrolled arterial hypertension (blood pressure >160/100mmHg at baseline)
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Cardiac failure (NYHA III-IV)
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Liver cirrhosis (Child B-C)
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Uncorrected adrenal or thyroidal deficiency
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Patients refusing or unable to give written informed consent
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Pregnancy or breast feeding
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End of life care
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hospital das clinicas Minas Gerais | Belo Horizonte | Brazil | ||
| 2 | University Hospital Würzburg | Würzburg | Germany | ||
| 3 | Granda Ospedale Maggiore Policlinico Milan | Milan | Italy | ||
| 4 | Erasmus MC | Rotterdam | Netherlands | ||
| 5 | University Hospital Basel, Department of Endocrinology | Basel | Basel Stadt | Switzerland | 4031 |
| 6 | University Hospital Zurich | Zürich | Switzerland | ||
| 7 | Cambridge University Hospital | Cambridge | United Kingdom |
Sponsors and Collaborators
- University Hospital, Basel, Switzerland
- University Hospital, Zürich
- Wuerzburg University Hospital
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
- Erasmus Medical Center
- Cambridge University Hospitals NHS Foundation Trust
- Federal University of Minas Gerais
Investigators
- Principal Investigator: Mirjam Christ-Crain, Prof, MD, University Hospital, Basel, Switzerland
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CARGOx