Ignite Creation Date:
2025-12-24 @ 4:39 PM
Ignite Modification Date:
2026-01-03 @ 7:07 PM
Study NCT ID:
NCT03572166
Status:
COMPLETED
Last Update Posted:
2023-07-27
First Post:
2018-06-04
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Use of Copeptin Measurement After Arginine Infusion for the Differential Diagnosis of Diabetes Insipidus - the CARGOx Study
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003919', 'term': 'Diabetes Insipidus'}, {'id': 'D059607', 'term': 'Polydipsia, Psychogenic'}], 'ancestors': [{'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}, {'id': 'D010900', 'term': 'Pituitary Diseases'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D059606', 'term': 'Polydipsia'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D001526', 'term': 'Behavioral Symptoms'}, {'id': 'D001519', 'term': 'Behavior'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'DIAGNOSTIC', 'interventionModel': 'CROSSOVER', 'interventionModelDescription': 'Observational randomized cross-over diagnostic international multicenter study'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 177}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2018-09-03', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-07', 'completionDateStruct': {'date': '2022-12-31', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-07-24', 'studyFirstSubmitDate': '2018-06-04', 'studyFirstSubmitQcDate': '2018-06-27', 'lastUpdatePostDateStruct': {'date': '2023-07-27', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2018-06-28', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-09-30', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'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', 'description': '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'}], 'secondaryOutcomes': [{'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)', 'description': 'Copeptin cut-offs used:\n\nArginine stimulation:\n\n* Copeptin level at 60 minutes \\< 2.4 pmol/l = complete central diabetes insipidus\n* Copeptin level at 60 minutes 2.4 - 3.8 pmol/l = partial central diabetes insipidus\n* Copeptin level at 60 minutes \\> 3.8 pmol/l = primary polydipsia\n\nHypertonic saline stimulation:\n\n* Copeptin level \\< 2.7 pmol/l = complete central diabetes insipidus\n* Copeptin level 2.7 - 4.9 pmol/l = partial central diabetes insipidus\n* Copeptin level \\> 4.9 pmol/l = primary polydipsia'}, {'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)', 'description': 'Copeptin cut-offs used:\n\nArginine stimulation:\n\n* Copeptin level at 60 minutes \\< 2.4 pmol/l = complete central diabetes insipidus\n* Copeptin level at 60 minutes 2.4 - 3.8 pmol/l = partial central diabetes insipidus\n* Copeptin level at 60 minutes \\> 3.8 pmol/l = primary polydipsia\n\nHypertonic saline stimulation:\n\n* Copeptin level \\< 2.7 pmol/l = complete central diabetes insipidus\n* Copeptin level 2.7 - 4.9 pmol/l = partial central diabetes insipidus\n* Copeptin level \\> 4.9 pmol/l = primary polydipsia'}, {'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)', 'description': 'Copeptin cut-offs used:\n\nArginine stimulation:\n\n* Copeptin level at 60 minutes \\< 2.4 pmol/l = complete central diabetes insipidus\n* Copeptin level at 60 minutes 2.4 - 3.8 pmol/l = partial central diabetes insipidus\n* Copeptin level at 60 minutes \\> 3.8 pmol/l = primary polydipsia\n\nHypertonic saline stimulation:\n\n* Copeptin level \\< 2.7 pmol/l = complete central diabetes insipidus\n* Copeptin level 2.7 - 4.9 pmol/l = partial central diabetes insipidus\n* Copeptin level \\> 4.9 pmol/l = primary polydipsia'}, {'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)', 'description': 'Copeptin cut-offs used:\n\nArginine stimulation:\n\n* Copeptin level at 60 minutes \\< 2.4 pmol/l = complete central diabetes insipidus\n* Copeptin level at 60 minutes 2.4 - 3.8 pmol/l = partial central diabetes insipidus\n* Copeptin level at 60 minutes \\> 3.8 pmol/l = primary polydipsia\n\nHypertonic saline stimulation:\n\n* Copeptin level \\< 2.7 pmol/l = complete central diabetes insipidus\n* Copeptin level 2.7 - 4.9 pmol/l = partial central diabetes insipidus\n* Copeptin level \\> 4.9 pmol/l = primary polydipsia'}, {'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)', 'description': 'assessed by visual analogue scale from 0 to 10, with 0 indicating no symptoms and 10 indicating severe symptoms.'}, {'measure': 'Frequency and severity of headache assessed by visual analogue scale during both tests', 'timeFrame': '2 days (1 for each test)', 'description': 'assessed by visual analogue scale from 0 to 10, with 0 indicating no symptoms and 10 indicating severe symptoms.'}, {'measure': 'Frequency and severity of nausea assessed by visual analogue scale during both tests', 'timeFrame': '2 days (1 for each test)', 'description': 'assessed by visual analogue scale from 0 to 10, with 0 indicating no symptoms and 10 indicating severe symptoms.'}, {'measure': 'Frequency and severity of vertigo assessed by visual analogue scale during both tests', 'timeFrame': '2 days (1 for each test)', 'description': 'assessed by visual analogue scale from 0 to 10, with 0 indicating no symptoms and 10 indicating severe symptoms.'}, {'measure': 'Frequency and severity of general malaise assessed by visual analogue scale during both tests', 'timeFrame': '2 days (1 for each test)', 'description': 'assessed by visual analogue scale from 0 to 10, with 0 indicating no symptoms and 10 indicating severe symptoms.'}, {'measure': 'Subjective burden assessed by visual analogue scale of both tests', 'timeFrame': '2 days (1 for each test)', 'description': 'assessed by visual analogue scale from 0 to 10, with 0 indicating no symptoms and 10 indicating severe symptoms.'}, {'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'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Copeptin'], 'conditions': ['Diabetes Insipidus', 'Polydipsia, Primary']}, 'referencesModule': {'references': [{'pmid': '40294614', 'type': 'DERIVED', 'citation': 'Atila C, Chifu I, Drummond JB, Vogt DR, Nahum U, Fassnacht M, Winzeler B, Refardt J, Christ-Crain M. A novel diagnostic score for diagnosing arginine vasopressin deficiency (central diabetes insipidus) or primary polydipsia with basal laboratory and clinical parameters: results from two international multicentre prospective diagnostic studies. Lancet Diabetes Endocrinol. 2025 Jun;13(6):505-515. doi: 10.1016/S2213-8587(25)00053-1. Epub 2025 Apr 25.'}, {'pmid': '39425917', 'type': 'DERIVED', 'citation': 'Bizzozero CA, Monnerat S, Chapman FA, Dhaun N, Refardt J, Christ-Crain M. Apelin levels in patients with polyuria-polydipsia syndrome upon copeptin stimulation tests. Eur J Endocrinol. 2024 Oct 29;191(5):491-498. doi: 10.1093/ejendo/lvae138.'}, {'pmid': '37966286', 'type': 'DERIVED', 'citation': 'Refardt J, Atila C, Chifu I, Ferrante E, Erlic Z, Drummond JB, Indirli R, Drexhage RC, Sailer CO, Widmer A, Felder S, Powlson AS, Hutter N, Vogt DR, Gurnell M, Soares BS, Hofland J, Beuschlein F, Fassnacht M, Winzeler B, Christ-Crain M. Arginine or Hypertonic Saline-Stimulated Copeptin to Diagnose AVP Deficiency. N Engl J Med. 2023 Nov 16;389(20):1877-1887. doi: 10.1056/NEJMoa2306263.'}]}, 'descriptionModule': {'briefSummary': '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.\n\nThe 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%.\n\nTo 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '95 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age ≥ 18 years\n* Hypotonic polyuria / polydipsia syndrome defined as: polyuria \\>50ml/kg body weight/24h and polydipsia \\>3l /24h or known diabetes insipidus under treatment with DDAVP\n* Urine-Osmolality \\<800mOsm/L\n\nExclusion Criteria:\n\n* Polyuria / polydipsia secondary to diabetes mellitus, hypercalcemia or hypokalemia\n* Nephrogenic diabetes insipidus (defined as baseline copeptin level \\>21.4pmol/L)\n* Evidence of any acute illness\n* Epilepsy requiring treatment\n* Uncontrolled arterial hypertension (blood pressure \\>160/100mmHg at baseline)\n* Cardiac failure (NYHA III-IV)\n* Liver cirrhosis (Child B-C)\n* Uncorrected adrenal or thyroidal deficiency\n* Patients refusing or unable to give written informed consent\n* Pregnancy or breast feeding\n* End of life care'}, 'identificationModule': {'nctId': 'NCT03572166', 'acronym': 'CARGOx', 'briefTitle': 'Use of Copeptin Measurement After Arginine Infusion for the Differential Diagnosis of Diabetes Insipidus - the CARGOx Study', 'organization': {'class': 'OTHER', 'fullName': 'University Hospital, Basel, Switzerland'}, 'officialTitle': 'Use of Copeptin Measurement After Arginine Infusion for the Differential Diagnosis of Diabetes Insipidus - the CARGOx Study', 'orgStudyIdInfo': {'id': 'CARGOx'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Arginine Infusion', 'description': 'Arginine Stimulation Test', 'interventionNames': ['Diagnostic Test: Arginine infusion']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Hypertonic saline infusion', 'description': 'Hypertonic Saline Infusion Test', 'interventionNames': ['Diagnostic Test: Hypertonic saline infusion']}], 'interventions': [{'name': 'Arginine infusion', 'type': 'DIAGNOSTIC_TEST', 'description': 'Intravenous Infusion of Arginine is given, copeptin measurement will be collected before and 60minutes after start of infusion', 'armGroupLabels': ['Arginine Infusion']}, {'name': 'Hypertonic saline infusion', 'type': 'DIAGNOSTIC_TEST', 'description': 'Intravenous Infusion of hypertonic Saline is given, copeptin measurement will be collected before and once Plasma sodium rises above 149mmol/l', 'armGroupLabels': ['Hypertonic saline infusion']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Belo Horizonte', 'country': 'Brazil', 'facility': 'Hospital das clinicas Minas Gerais', 'geoPoint': {'lat': -19.92083, 'lon': -43.93778}}, {'city': 'Würzburg', 'country': 'Germany', 'facility': 'University Hospital Würzburg', 'geoPoint': {'lat': 49.79391, 'lon': 9.95121}}, {'city': 'Milan', 'country': 'Italy', 'facility': 'Granda Ospedale Maggiore Policlinico Milan', 'geoPoint': {'lat': 45.46427, 'lon': 9.18951}}, {'city': 'Rotterdam', 'country': 'Netherlands', 'facility': 'Erasmus MC', 'geoPoint': {'lat': 51.9225, 'lon': 4.47917}}, {'zip': '4031', 'city': 'Basel', 'state': 'Canton of Basel-City', 'country': 'Switzerland', 'facility': 'University Hospital Basel, Department of Endocrinology', 'geoPoint': {'lat': 47.55839, 'lon': 7.57327}}, {'city': 'Zurich', 'country': 'Switzerland', 'facility': 'University Hospital Zurich', 'geoPoint': {'lat': 47.36667, 'lon': 8.55}}, {'city': 'Cambridge', 'country': 'United Kingdom', 'facility': 'Cambridge University Hospital', 'geoPoint': {'lat': 52.2, 'lon': 0.11667}}], 'overallOfficials': [{'name': 'Mirjam Christ-Crain, Prof, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University Hospital, Basel, Switzerland'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University Hospital, Basel, Switzerland', 'class': 'OTHER'}, 'collaborators': [{'name': 'University Hospital, Zürich', 'class': 'OTHER'}, {'name': 'Wuerzburg University Hospital', 'class': 'OTHER'}, {'name': "Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico", 'class': 'OTHER'}, {'name': 'Erasmus Medical Center', 'class': 'OTHER'}, {'name': 'Cambridge University Hospitals NHS Foundation Trust', 'class': 'OTHER'}, {'name': 'Federal University of Minas Gerais', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}