Copeptin in the Diagnosis and Differential Diagnosis of Diabetes Insipidus. The CoSIP-Study

• ClinicalTrials.gov Identifier: NCT00757276
• Recruitment Status: Completed
• First Posted: September 23, 2008
• Last Update Posted: December 15, 2014
• Sponsor: University Hospital, Basel, Switzerland
• Information provided by (Responsible Party): University Hospital, Basel, Switzerland

Study Description

Brief Summary:

Evaluation of Copeptin in the differential diagnosis of diabetes insipidus.

Condition or disease
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.

Study Design

• Study Type: Observational
• Actual Enrollment: 50 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Copeptin in the Diagnosis and Differential Diagnosis of Diabetes Insipidus. The CoSIP-Study
• Study Start Date: June 2008
• Actual Primary Completion Date: October 2014
• Actual Study Completion Date: October 2014

Groups and Cohorts

Group/Cohort

1; 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. The investigators hypothesize that basal copeptin levels can reliably differentiate between the 5 groups(central, nephrogenic, psychogenic and partial forms) with a sensitivity and specificity >80%.

Outcome Measures

Primary Outcome Measures :

1. Diagnosis of diabetes insipidus(DI) centralis versus psychogenic DI [ Time Frame: 2 years ]

Biospecimen Retention:   Samples Without DNA

bood sampling

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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.

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

Contacts and Locations

Locations

Switzerland

University Hospital Basel

Basel, Switzerland, 4031

Sponsors and Collaborators

University Hospital, Basel, Switzerland

Investigators

• Principal Investigator: Mirjam Christ-Crain, Prof. Dr. med.; University Hospital, Basel, Switzerland

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

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.

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.

• Responsible Party: University Hospital, Basel, Switzerland
• ClinicalTrials.gov Identifier: NCT00757276
• Other Study ID Numbers: EKBB 68/08
• First Posted: September 23, 2008
• Last Update Posted: December 15, 2014
• Last Verified: December 2014

Keywords provided by University Hospital, Basel, Switzerland:

Copeptin; Diabetes insipidus; diagnostic marker; Vasopressin; antidiuretic hormone (ADH)

Additional relevant MeSH terms:

Diabetes Insipidus; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pituitary Diseases