Ignite Creation Date:
2025-12-24 @ 4:56 PM
Ignite Modification Date:
2025-12-24 @ 4:56 PM
Study NCT ID:
NCT03973450
Status:
UNKNOWN
Last Update Posted:
2021-09-08
First Post:
2019-05-25
Is Possible Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Epidemiology of Pituitary Tumours: Prevalence of Associated Neoplasia
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D010911', 'term': 'Pituitary Neoplasms'}, {'id': 'D004701', 'term': 'Endocrine Gland Neoplasms'}, {'id': 'D006961', 'term': 'Hyperparathyroidism'}, {'id': 'D009386', 'term': 'Neoplastic Syndromes, Hereditary'}], 'ancestors': [{'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D007029', 'term': 'Hypothalamic Neoplasms'}, {'id': 'D015173', 'term': 'Supratentorial Neoplasms'}, {'id': 'D001932', 'term': 'Brain Neoplasms'}, {'id': 'D016543', 'term': 'Central Nervous System Neoplasms'}, {'id': 'D009423', 'term': 'Nervous System Neoplasms'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D007027', 'term': 'Hypothalamic Diseases'}, {'id': 'D010900', 'term': 'Pituitary Diseases'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D010279', 'term': 'Parathyroid Diseases'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'RETROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 400}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'RECRUITING', 'startDateStruct': {'date': '2019-06-15', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-08', 'completionDateStruct': {'date': '2022-02-28', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2021-08-31', 'studyFirstSubmitDate': '2019-05-25', 'studyFirstSubmitQcDate': '2019-05-31', 'lastUpdatePostDateStruct': {'date': '2021-09-08', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2019-06-04', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-11-30', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Prevalence of hyperparathyroidism (HPT)', 'timeFrame': 'Up to 6 months', 'description': 'measurement of plasma Parathormone (PTH) in % of upper limit of normal values (ULN)'}, {'measure': 'Prevalence of hypercalcemia (hypercalcemic hyperparathyroidism)', 'timeFrame': 'Up to 6 months', 'description': 'measurement of calcemia (mg/dl)'}, {'measure': 'Search for secondary cause of hyperparathyroidism (1): vit D deficiency', 'timeFrame': 'Up to 6 months (where indicated)', 'description': 'measurement of plasma 25(OH)D (ng/ml)'}, {'measure': 'Search for secondary cause of hyperparathyroidism (2): renal failure', 'timeFrame': 'Up to 6 months', 'description': 'measurement of plasma creatinine (mg/dl)'}, {'measure': 'Prevalence of thyroid nodules', 'timeFrame': 'Up to 6 months', 'description': 'Thyroid ultrasound'}, {'measure': 'Prevalence of other endocrine and non-endocrine neoplasia (1)', 'timeFrame': 'Up to 6 months', 'description': 'Report of any neoplasia before the diagnosis of PiT'}, {'measure': 'Prevalence of other endocrine and non-endocrine neoplasia (2)', 'timeFrame': 'Up to 6 months', 'description': 'Report of any neoplasia diagnosed during the follow-up of PiT'}, {'measure': 'Familial setting (1)', 'timeFrame': 'Up to 6 months', 'description': 'Report of any available information concerning familiarity for PiT'}, {'measure': 'Familial setting (2)', 'timeFrame': 'up to 6 months', 'description': 'Familiarity for any associated neoplasia'}], 'secondaryOutcomes': [{'measure': 'Genetics (1) familial forms of PiT', 'timeFrame': 'up to 15 months', 'description': 'AIP gene sequencing upon genetic counselling'}, {'measure': 'Genetics (2) familial PiT and/or association with HPT', 'timeFrame': 'up to 15 months', 'description': 'MEN1 sequencing upon genetic counselling'}, {'measure': 'Genetics (3) any other clinical suspicion for MEN1', 'timeFrame': 'up to 15 months', 'description': 'MEN1 gene sequencing upon genetic counselling'}, {'measure': 'Genetics (4) any other clinical suspicion of inherited neoplasia syndrome', 'timeFrame': 'up to 15 months', 'description': 'genetic counselling for appropriate gene sequencing'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Pituitary Tumor', 'Endocrine Neoplasia', 'Hyperparathyroidism', 'Solid Tumor', 'Familial Tumor Syndrome']}, 'referencesModule': {'references': [{'pmid': '16968795', 'type': 'BACKGROUND', 'citation': 'Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A. High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium. J Clin Endocrinol Metab. 2006 Dec;91(12):4769-75. doi: 10.1210/jc.2006-1668. Epub 2006 Sep 12.'}, {'pmid': '19650784', 'type': 'BACKGROUND', 'citation': 'Fernandez A, Karavitaki N, Wass JA. Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clin Endocrinol (Oxf). 2010 Mar;72(3):377-82. doi: 10.1111/j.1365-2265.2009.03667.x. Epub 2009 Jul 24.'}, {'pmid': '27742789', 'type': 'BACKGROUND', 'citation': 'Caimari F, Korbonits M. Novel Genetic Causes of Pituitary Adenomas. Clin Cancer Res. 2016 Oct 15;22(20):5030-5042. doi: 10.1158/1078-0432.CCR-16-0452.'}, {'pmid': '9425388', 'type': 'BACKGROUND', 'citation': 'Corbetta S, Pizzocaro A, Peracchi M, Beck-Peccoz P, Faglia G, Spada A. Multiple endocrine neoplasia type 1 in patients with recognized pituitary tumours of different types. Clin Endocrinol (Oxf). 1997 Nov;47(5):507-12. doi: 10.1046/j.1365-2265.1997.3311122.x.'}, {'pmid': '28824003', 'type': 'BACKGROUND', 'citation': 'Alrezk R, Hannah-Shmouni F, Stratakis CA. MEN4 and CDKN1B mutations: the latest of the MEN syndromes. Endocr Relat Cancer. 2017 Oct;24(10):T195-T208. doi: 10.1530/ERC-17-0243. Epub 2017 Aug 19.'}, {'pmid': '22723327', 'type': 'BACKGROUND', 'citation': 'Thakker RV, Newey PJ, Walls GV, Bilezikian J, Dralle H, Ebeling PR, Melmed S, Sakurai A, Tonelli F, Brandi ML; Endocrine Society. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012 Sep;97(9):2990-3011. doi: 10.1210/jc.2012-1230. Epub 2012 Jun 20.'}, {'pmid': '28274953', 'type': 'BACKGROUND', 'citation': 'Olsson DS, Hammarstrand C, Bryngelsson IL, Nilsson AG, Andersson E, Johannsson G, Ragnarsson O. Incidence of malignant tumours in patients with a non-functioning pituitary adenoma. Endocr Relat Cancer. 2017 May;24(5):227-235. doi: 10.1530/ERC-16-0518. Epub 2017 Mar 8.'}, {'pmid': '28710115', 'type': 'BACKGROUND', 'citation': 'Terzolo M, Reimondo G, Berchialla P, Ferrante E, Malchiodi E, De Marinis L, Pivonello R, Grottoli S, Losa M, Cannavo S, Ferone D, Montini M, Bondanelli M, De Menis E, Martini C, Puxeddu E, Velardo A, Peri A, Faustini-Fustini M, Tita P, Pigliaru F, Peraga G, Borretta G, Scaroni C, Bazzoni N, Bianchi A, Berton A, Serban AL, Baldelli R, Fatti LM, Colao A, Arosio M; Italian Study Group of Acromegaly. Acromegaly is associated with increased cancer risk: a survey in Italy. Endocr Relat Cancer. 2017 Sep;24(9):495-504. doi: 10.1530/ERC-16-0553. Epub 2017 Jul 14.'}, {'pmid': '26113600', 'type': 'BACKGROUND', 'citation': "O'Toole SM, Denes J, Robledo M, Stratakis CA, Korbonits M. 15 YEARS OF PARAGANGLIOMA: The association of pituitary adenomas and phaeochromocytomas or paragangliomas. Endocr Relat Cancer. 2015 Aug;22(4):T105-22. doi: 10.1530/ERC-15-0241. Epub 2015 Jun 25."}, {'pmid': '23371967', 'type': 'BACKGROUND', 'citation': 'Beckers A, Aaltonen LA, Daly AF, Karhu A. Familial isolated pituitary adenomas (FIPA) and the pituitary adenoma predisposition due to mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. Endocr Rev. 2013 Apr;34(2):239-77. doi: 10.1210/er.2012-1013. Epub 2013 Jan 31.'}, {'pmid': '28923463', 'type': 'BACKGROUND', 'citation': 'Bilezikian JP, Bandeira L, Khan A, Cusano NE. Hyperparathyroidism. Lancet. 2018 Jan 13;391(10116):168-178. doi: 10.1016/S0140-6736(17)31430-7. Epub 2017 Sep 17.'}, {'pmid': '30290451', 'type': 'RESULT', 'citation': 'Jaffrain-Rea ML, Daly AF, Angelini M, Petrossians P, Bours V, Beckers A. Genetic susceptibility in pituitary adenomas: from pathogenesis to clinical implications. Expert Rev Endocrinol Metab. 2011 Mar;6(2):195-214. doi: 10.1586/eem.10.87.'}, {'pmid': '17244780', 'type': 'RESULT', 'citation': 'Daly AF, Vanbellinghen JF, Khoo SK, Jaffrain-Rea ML, Naves LA, Guitelman MA, Murat A, Emy P, Gimenez-Roqueplo AP, Tamburrano G, Raverot G, Barlier A, De Herder W, Penfornis A, Ciccarelli E, Estour B, Lecomte P, Gatta B, Chabre O, Sabate MI, Bertagna X, Garcia Basavilbaso N, Stalldecker G, Colao A, Ferolla P, Wemeau JL, Caron P, Sadoul JL, Oneto A, Archambeaud F, Calender A, Sinilnikova O, Montanana CF, Cavagnini F, Hana V, Solano A, Delettieres D, Luccio-Camelo DC, Basso A, Rohmer V, Brue T, Bours V, Teh BT, Beckers A. Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families. J Clin Endocrinol Metab. 2007 May;92(5):1891-6. doi: 10.1210/jc.2006-2513. Epub 2007 Jan 23.'}]}, 'descriptionModule': {'briefSummary': 'The study aims to update current knowledge about the epidemiology of pituitary tumours (PiT), based on the wide body of scientific literature on new familial and/or syndromic forms. Although inherited predisposition is increasingly recognized, its clinical relevance in unselected series of PiT patients has not been specifically addressed. In addition, it is likely that further recognition of peculiar associations between PiT and other endocrine and/or non-endocrine neoplasia will further increase the spectrum of syndromic forms. Since the identification of inherited forms of PiT may have significant clinical implications in terms of patients management and familial screening, we aim to collect any relevant information in order to estimate their prevalence in a large unselected series of PiT patients and provide new clues for a modern clinical approach to these patients.', 'detailedDescription': 'Recent epidemiological studies indicate that clinically relevant PiT have a prevalence around 1%. The Neuromed Scientific Institute for Research and Cure (IRCCS) is a third referral center for the diagnosis and treatment of patients with hypothalamic-pituitary disorders, and PiT represent the most frequent condition.\n\nThe best known syndromic of PiT is Multiple Endocrine Neoplasia type 1 (MEN1), others are rare conditions, such as MEN1-like syndromes, Carney complex, Mc Cune Albright syndrome, the pheochromocytoma/paraganglioma/Pit syndrome. Apparently isolated familial forms of PiT (FIPA) have also been well characterized in the last decade.The genetics of inherited PiT is involving a growing number of genes.At the moment, the most frequently reported gene abnormalities consist of inactivating mutations of the MEN1 and Aryl hydrocarbon receptor Interacting Protein (AIP) genes, which are mainly observed in syndromic and isolated familial forms of PiT, respectively.\n\nOn the other hand, patients affected by growth-hormone (GH)-secreting PiT (acromegaly/gigantism) have an increased risk of associated neoplasia, which has been mainly attributed to the growth-promoting effects of GH and/or Insulin-like Growth Factor 1(IGF1). However, a variety of neoplasia have been recently observed in patients with non-functioning PiT, whereas patients affected by prolactinoma - the most common PiT phenotype - have been poorly studied. Associations between PiT and a variety of neoplasia may represent new forms of systemic forms of PiT.\n\nThe aim of the study is to evaluate the prevalence of endocrine and non-endocrine neoplasia in a large series of PiTpatients and to identify potential familial and syndromic forms, including new forms of tumor associations, in order to provide new insights in the epidemiology and genetics of PiT and evaluate their clinical relevance in daily practice.\n\nEligible patients will receive a detailed informative form about the aim, methods and potential implications of the study. They will be included upon written informed consent and be re-assured that they may refuse to participate or withdraw from the study at any time, without any prejudice in their clinical management.\n\nData will be collected retrospectively in patients followed-up in the last 5 years, when an increased awareness of systemic conditions has lead, in the respect of good clinical practice, to a systematic registration of familiarity for PiT and/or for associated neoplasia. As clinically recommended, most patients have been screened at least once for primary hyperparathyroidism (pHPT), which is the most prevalent endocrine tumor in MEN1, and thyroid ultrasound, which is generally proposed as an extension of any endocrinological visit. Therefore, parathyroid and/or thyroid tumours should have been correctly identified in a large majority of patients. In contrast, except for systemic search for colonic polyps or tumours by coloscopy in acromegalic patients, and screening for breast and colon cancer performed by the patients in the setting of the Italian National Health System (NHS) programme since the age of 50 yr-old, no systematic search for additional tumours was performed and diagnoses were typically made by the general practitioner and other specialists.\n\nAny relevant clinical, biological or imaging data about PiT and extrapituitary tumours will be collected for each patients.\n\nAll data will be collected anonymously in a dedicated Excel file.\n\nStatistical analysis will be performed with using a commercially available software - JMP version 11.0 distributed by Statistical Analysis Systems (SAS) (USA). The first part of the report will be descriptive, report all endocrine and non-endocrine neoplasia and potential familiarity for PiT and/or any other associated neoplasia. Then, a comparison will be made between groups and subgroups of PiT patients defined according to the PiT phenotype (functioning and nonfunctioning PiT subgroups, tumour volume and invasiveness), as well as gender, age and the presence of a familial setting. Based on public reports of the Italian registry of cancer (AIRTUM), an attempt will be made to compare the prevalence of the most frequent neoplasia in PiT patients with the general population. Attention will be paid to recognize syndromic forms of PiT, including known syndromes and new forms of associations between PiT and any endocrine or non-endocrine neoplasia.\n\nGenetic evaluation and counselling will be proposed in selected cases, based on evaluation of the clinical picture with the specialist in clinical genetics present in the study team. A specific additional consent will be necessary to proceed to the genetic step and DNA conservation for further studies where appropriate. Leukocyte DNA will be collected by blood sampling. Diagnostic genetic testing will be appropriately performed according to the clinical presentation. For unknown associations, this study is intended to be preliminary to further genetic studies aiming to identify new candidate genes.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'We estimate that more than 500 patients followed at the Neuroendocrinology unit meet the eligibility criteria for the study period, and that a majority of them will accept to enter the study. Patients are affected prevalently by functional pituitary tumours (prolactinomas about 50%, followed by acromegaly about 20%, corticotroph tumours..), others have clinically non-functiong pituitary tumours (about 25%). The large majority of patients are adult (\\> 90 %).', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Any patient affected by a documented endocrine pituitary tumour (PiT)\n* At least one evaluation during the study period (2014-2018)\n\nExclusion Criteria:\n\n* Uncertain diagnosis of endocrine pituitary tumour\n* Any adult patient declining to enter the study\n* For the (few) patients aged less than 18 years, parents or legal tutors declining to include the patient in the study'}, 'identificationModule': {'nctId': 'NCT03973450', 'acronym': 'EpidemioPIT', 'briefTitle': 'Epidemiology of Pituitary Tumours: Prevalence of Associated Neoplasia', 'organization': {'class': 'OTHER', 'fullName': 'Neuromed IRCCS'}, 'officialTitle': 'Epidemiology of Pituitary Tumours: Prevalence of Associated Endocrine and Non-endocrine Tumours and Potential Implications in the Management and Follow-up of Patients"', 'orgStudyIdInfo': {'id': 'Neuroendo-1'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Pituitary tumours', 'description': 'Patients affected by pituitary tumours and followed-up at the Neuroendocrinology Unit over a 5 yrs period (2014-2018)', 'interventionNames': ['Other: Registration of familial forms and associated neoplasia']}], 'interventions': [{'name': 'Registration of familial forms and associated neoplasia', 'type': 'OTHER', 'otherNames': ['Genetic counselling where appropriate'], 'description': 'Retrospective registration of associated endocrine and non-endocrine neoplasia and potential familial setting', 'armGroupLabels': ['Pituitary tumours']}]}, 'contactsLocationsModule': {'locations': [{'zip': '86077', 'city': 'Pozzilli', 'state': 'IS', 'status': 'RECRUITING', 'country': 'Italy', 'contacts': [{'name': 'Marie-Lise Jaffrain-Rea, MD', 'role': 'CONTACT', 'email': 'marielise.jaffrain@univaq.it', 'phone': '+393487813716'}, {'name': 'Alba Di Pardo, PhD', 'role': 'CONTACT', 'email': 'alba.dipardo78@gmail.com', 'phone': '+393483631480'}], 'facility': 'Neuromed', 'geoPoint': {'lat': 41.51142, 'lon': 14.06252}}], 'centralContacts': [{'name': 'Marie-Lise Jaffrain-Rea, MD', 'role': 'CONTACT', 'email': 'marielise.jaffrain@univaq.it', 'phone': '+393487813716'}, {'name': 'Alba Di Pardo, MD', 'role': 'CONTACT', 'email': 'dipardoa@hotmail.com', 'phone': '+393483631480'}], 'overallOfficials': [{'name': 'Marie-Lise Jaffrain-Rea, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Neuromed IRCCS, Pozzilli (IS), Italy'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Neuromed IRCCS', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Associate Professor of Endocrinology', 'investigatorFullName': 'Marie-Lise Jaffrain-Rea, MD', 'investigatorAffiliation': 'Neuromed IRCCS'}}}}