Clinical trial NCT00757276: Copeptin in the Diagnosis and Differential Diagnosis of Diabetes Insipidus. The CoSIP-Study
Official title: Copeptin in the Diagnosis and Differential Diagnosis of Diabetes Insipidus. The CoSIP-Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diabetes Insipidus
Keywords: Copeptin
Diabetes insipidus
diagnostic marker
Vasopressin
antidiuretic hormone (ADH)
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2008-09-23
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: All patients \>18 years who are tested for the diagnosis of DI because of a history of polyuria (\>40ml/kg per 24 hours) in the presence of polydipsia Patients with known DI will be contacted whether they agree to participate in the study and to undergo again a water deprivation test to measure copeptin to confirm the diagnosis.

Brief summary: Evaluation of Copeptin in the differential diagnosis of diabetes insipidus.

Detailed description: Background:

Plasma arginine vasopressin (AVP) measurement is recommended for the differential diagnosis of diabetes insipidus and polydipsia. However, AVP measurement is cumbersome. AVP is derived from a larger precursor peptide along with copeptin, which is a more stable peptide directly mirroring the production of AVP. Copeptin can be assayed readily in plasma.

Aim: To evaluate the diagnostic accuracy of copeptin levels in the diagnosis and differential diagnosis of diabetes insipidus.

Design: Prospective, observational multicenter study.

Setting: Department of Endocrinology, University Hospital of Basel

Patients: Patients with suspected or known central (complete or partial), nephrogenic (complete or partial) or psychogenic diabetes insipidus undergoing a standardized water deprivation test.

Intervention: All patients with suspected or known diabetes insipidus will undergo an overnight water deprivation test and a standardized water deprivation test, as routinely performed in the diagnostic evaluation of diabetes insipidus. Plasma AVP and copeptin will be measured at baseline (8 am before start of thirsting), and hourly during the water deprivation test.

Study hypothesis: Copeptin levels will provide a better diagnostic accuracy in the diagnosis and differential diagnosis of diabetes insipidus as compared to AVP measurement.

Analysis: We will study 5 groups of patients: A) Patients with complete central diabetes insipidus, B) Patients with partial central diabetes insipidus, C) Patients with complete nephrogenic diabetes insipidus, D) Patients with partial nephrogenic diabetes insipidus and E) Patients with psychogenic diabetes insipidus. All groups will consist of 10 patients based on the following assumptions: Based on pilot studies we assume that patients in group A) will have copeptin values of 2.5 ± 1.0; Group B) 3.0 ± 1.0, Group C) 15.0 ± 5; Group D) 6 ± 2.0 and Group E) 4.0 ± 1.0 pmol/L. This results in a power of 90% to detect a difference in copeptin levels of 0.8pmol/L between the closest two groups, i.e. patients with partial central Diabetes insipidus and patients with psychogenic Diabetes insipidus.

Significance: The measurement of copeptin will allow a better discrimination of patients with diabetes insipidus, especially for the discrimination of partial central and nephrogenic and psychogenic diabetes insipidus.

Eligibility criteria: Inclusion Criteria:

* All patients \> 18 years who are tested for the diagnosis of DI because of a history of polyuria (\> 40 ml/kg per 24 hours) in the presence of polydipsia Patients with known DI will be contacted whether they agree to participate in the study and to undergo again a water deprivation test to measure copeptin to confirm the diagnosis.

Exclusion Criteria:

* Polyuria of other origin, i.e. prostate hyperplasia, diabetes mellitus.
* Pregnancy
* The investigators do not perform the water deprivation test in patients with: \*renal insufficiency

  * uncontrolled diabetes mellitus
  * hypovolemia of any cause
  * uncorrected deficiency of adrenal or thyroid hormones
* No informed consent

Primary outcomes:
measure: Diagnosis of diabetes insipidus(DI) centralis versus psychogenic DI
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Mirjam Christ-Crain, Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ebrahimi F, Urwyler SA, Betz MJ, Christ ER, Schuetz P, Mueller B, Donath MY, Christ-Crain M. Effects of interleukin-1 antagonism and corticosteroids on fibroblast growth factor-21 in patients with metabolic syndrome. Sci Rep. 2021 Apr 12;11(1):7911. doi: 10.1038/s41598-021-87207-w.
citation: Bologna K, Cesana-Nigro N, Refardt J, Imber C, Vogt DR, Christ-Crain M, Winzeler B. Effect of Arginine on the Hypothalamic-Pituitary-Adrenal Axis in Individuals With and Without Vasopressin Deficiency. J Clin Endocrinol Metab. 2020 Jul 1;105(7):dgaa157. doi: 10.1210/clinem/dgaa157.
citation: Winzeler B, Cesana-Nigro N, Refardt J, Vogt DR, Imber C, Morin B, Popovic M, Steinmetz M, Sailer CO, Szinnai G, Chifu I, Fassnacht M, Christ-Crain M. Arginine-stimulated copeptin measurements in the differential diagnosis of diabetes insipidus: a prospective diagnostic study. Lancet. 2019 Aug 17;394(10198):587-595. doi: 10.1016/S0140-6736(19)31255-3. Epub 2019 Jul 11.
citation: Urwyler SA, Timper K, Fenske W, de Mota N, Blanchard A, Kuhn F, Frech N, Arici B, Rutishauser J, Kopp P, Stettler C, Muller B, Katan M, Llorens-Cortes C, Christ-Crain M. Plasma Apelin Concentrations in Patients With Polyuria-Polydipsia Syndrome. J Clin Endocrinol Metab. 2016 May;101(5):1917-23. doi: 10.1210/jc.2016-1158. Epub 2016 Mar 11.
citation: Timper K, Fenske W, Kuhn F, Frech N, Arici B, Rutishauser J, Kopp P, Allolio B, Stettler C, Muller B, Katan M, Christ-Crain M. Diagnostic Accuracy of Copeptin in the Differential Diagnosis of the Polyuria-polydipsia Syndrome: A Prospective Multicenter Study. J Clin Endocrinol Metab. 2015 Jun;100(6):2268-74. doi: 10.1210/jc.2014-4507. Epub 2015 Mar 13.