Prevalence of Spontaneous Pneumothorax in BHD

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ClinicalTrials.gov Identifier: NCT02916992

Recruitment Status : Unknown

Verified October 2016 by Hans Smit, Free University Medical Center.
Recruitment status was: Recruiting

First Posted : September 28, 2016

Last Update Posted : October 26, 2016

Sponsor:

Collaborators:

Prof. Dr. Jaap Swieringa stichting

Mr. Willem Bakhuys Roozeboomstichting

Rijnstate Hospital

Information provided by (Responsible Party):

Hans Smit, Free University Medical Center

Study Description

Brief Summary:

To assess the prevalence of BHD (Birt-Hogg-Dubé syndrome) among patients with spontaneous pneumothorax. Patients who were treated for primary spontaneous pneumothorax in Rijnstate hospital are to be included. Patients will receive a questionnaire. When given consent, the investigators will invite them for a one-time visit to the out-patient clinic. Patients will be asked for a blood sample to determine pathogenic FLCN (folliculin) mutations and a pulmonary CT scan for evaluation of presence of lung cysts.

Condition or disease	Intervention/treatment	Phase
Spontaneous Pneumothorax	Radiation: CT scan of the thorax Genetic: blood sample for FLCN mutation analyses	Phase 1

Detailed Description:

Based on the results of the pilot study in VUmc *Free University Medical Center), in which 3 out of 40 tested patients had a pathological FLCN mutation, the investigators decided to extend the study to a second center; Rijnstate Hospital Arnhem. In this hospital a retrospective search was performed; patients who were treated for primary spontaneous pneumothorax were included. In the dossiers the investigators searched for medical history, pneumothorax side and recurrence, diagnostic imaging, treatment, co-morbidity, complications of treatment, skin abnormalities, kidney disease, smoking behavior, medication, and familial incidence of pneumothorax and other diseases. Patients will receive a letter with explanation of the research and a questionnaire in which the investigators ask them their about the medical status, co-morbidity, pneumothorax (number and side), smoking behavior, use of drugs, familial incidence of pneumothorax and other diseases.

The population will be formed out of patients who have returned the fully filled in questionnaire and who have given permission to receive information for further research. This further information will consist of an information letter on BHD syndrome and a consent form for a one-time visit to the out-patient clinic of Rijnstate hospital. Investigators expect that about 200 patients will return the fully filled in questionnaire and give their consent for further research. In a one-time visit in out-patient clinic, there will be given personal information on BHD syndrome and there will be performed physical examination for finding fibrofolliculomas. A pulmonary CT scan for evaluation of presence of lung cysts will be performed. Two samples of venous blood will be collected to access information on DNA diagnostics for pathogenic FLCN mutations. These are associated with the BHD syndrome. This last diagnostic testing will be performed in VUmc (Vrije Universiteit medisch centrum or Free University Medical Centre).

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	200 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Screening
Official Title:	Prevalence of Birt-Hogg-Dubé Syndrome Among Patients With (Hereditary) Spontaneous Pneumothorax
Study Start Date :	September 2016
Estimated Primary Completion Date :	June 2017
Estimated Study Completion Date :	July 2017

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Birt-Hogg-Dubé syndrome Primary spontaneous pneumothorax

MedlinePlus related topics: Collapsed Lung

Genetic and Rare Diseases Information Center resources: Primary Spontaneous Pneumothorax Birt-Hogg-Dube Syndrome

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Spontaneous pneumothorax patients 1 Patients who were treated for spontaneous pneumothorax in Rijnstate hospital. "Interventions": visit to out-patient clinic,CT scan of pulmones.	Radiation: CT scan of the thorax A low dose CT scan of the thorax (2mSv) wil be performed once. Genetic: blood sample for FLCN mutation analyses A venous punction in order to withdraw 16ml blood is undertaken once.
Active Comparator: Spontaneous pneumothorax patients 2 Patients who were treated for spontaneous pneumothorax in Rijnstate hospital. "Interventions": withdrawal of blood sample for DNA analyses,	Radiation: CT scan of the thorax A low dose CT scan of the thorax (2mSv) wil be performed once. Genetic: blood sample for FLCN mutation analyses A venous punction in order to withdraw 16ml blood is undertaken once.

Outcome Measures

Primary Outcome Measures :

presence of pathogenic FLCN mutations [ Time Frame: 6 months ]
by assessing blood samples

Secondary Outcome Measures :

presence of lung cysts [ Time Frame: 6 months ]
visible on pulmonary low dose CT

Eligibility Criteria

Information from the National Library of Medicine

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

Criteria

Inclusion Criteria:

treated in Rijnstate hospital for primary spontaneous pneumothorax
informed consent

Exclusion Criteria:

secondary or iatrogenic pneumothorax

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02916992

Contacts

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Contact: Jincey D. Sriram, MD, MSc	0880058888 ext 3443	JSriram@Rijnstate.nl
Contact: Hans JM Smit, MD,PhD	0880058888 ext 3030	HSmit@Rijnstate.nl

Locations

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Netherlands
Rijnstate	Recruiting
Arnhem, Gelderland, Netherlands, 68015AD
Contact: Hans JM Smit, MD. PhD 0031880058888 hsmit@rijnstate.nl
Contact: Jincey Sriram, MD 0031880058888 JSriram@rijnstate.nl

Sponsors and Collaborators

Hans Smit

Prof. Dr. Jaap Swieringa stichting

Mr. Willem Bakhuys Roozeboomstichting

Rijnstate Hospital

Investigators

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Study Chair:	Pieter E. Postmus, MD, PhD	The Clatterbridge Cancer Centre
Principal Investigator:	Hans JM Smit, MD, PhD	Rijnstate Hospital

More Information

Study Data/Documents: Study Protocol This link exits the ClinicalTrials.gov site

Identifier: NL50605.091.14
ABR form (Algemeen Beoordelings en Registratie formulier; document of dutch board of human research (Centrale Commissie Mensgebonden Onderzoek)

Publications:

Johannesma PC, Thunnissen E, Postmus PE. Lung cysts as indicator for Birt-Hogg-Dubé syndrome. Lung. 2014 Feb;192(1):215-6. doi: 10.1007/s00408-013-9522-0. Epub 2013 Oct 22.

Toro JR, Wei MH, Glenn GM, Weinreich M, Toure O, Vocke C, Turner M, Choyke P, Merino MJ, Pinto PA, Steinberg SM, Schmidt LS, Linehan WM. BHD mutations, clinical and molecular genetic investigations of Birt-Hogg-Dubé syndrome: a new series of 50 families and a review of published reports. J Med Genet. 2008 Jun;45(6):321-31. doi: 10.1136/jmg.2007.054304. Epub 2008 Jan 30. Review.

Houweling AC, Gijezen LM, Jonker MA, van Doorn MB, Oldenburg RA, van Spaendonck-Zwarts KY, Leter EM, van Os TA, van Grieken NC, Jaspars EH, de Jong MM, Bongers EM, Johannesma PC, Postmus PE, van Moorselaar RJ, van Waesberghe JH, Starink TM, van Steensel MA, Gille JJ, Menko FH. Renal cancer and pneumothorax risk in Birt-Hogg-Dubé syndrome; an analysis of 115 FLCN mutation carriers from 35 BHD families. Br J Cancer. 2011 Dec 6;105(12):1912-9. doi: 10.1038/bjc.2011.463.

Toro JR, Pautler SE, Stewart L, Glenn GM, Weinreich M, Toure O, Wei MH, Schmidt LS, Davis L, Zbar B, Choyke P, Steinberg SM, Nguyen DM, Linehan WM. Lung cysts, spontaneous pneumothorax, and genetic associations in 89 families with Birt-Hogg-Dubé syndrome. Am J Respir Crit Care Med. 2007 May 15;175(10):1044-53. Epub 2007 Feb 22.

Johannesma PC, Reinhard R, Kon Y, Sriram JD, Smit HJ, van Moorselaar RJ, Menko FH, Postmus PE; Amsterdam BHD working group. Prevalence of Birt-Hogg-Dubé syndrome in patients with apparently primary spontaneous pneumothorax. Eur Respir J. 2015 Apr;45(4):1191-4. doi: 10.1183/09031936.00196914. Epub 2014 Dec 23.

Johannesma PC, Lammers JW, van Moorselaar RJ, Starink TM, Postmus PE, Menko FH. [Spontaneous pneumothorax as the first manifestation of a hereditary condition with an increased renal cancer risk]. Ned Tijdschr Geneeskd. 2009;153:A581. Dutch.

Ren HZ, Zhu CC, Yang C, Chen SL, Xie J, Hou YY, Xu ZF, Wang DJ, Mu DK, Ma DH, Wang Y, Ye MH, Ye ZR, Chen BF, Wang CG, Lin J, Qiao D, Yi L. Mutation analysis of the FLCN gene in Chinese patients with sporadic and familial isolated primary spontaneous pneumothorax. Clin Genet. 2008 Aug;74(2):178-83. doi: 10.1111/j.1399-0004.2008.01030.x. Epub 2008 May 25.

Warren MB, Torres-Cabala CA, Turner ML, Merino MJ, Matrosova VY, Nickerson ML, Ma W, Linehan WM, Zbar B, Schmidt LS. Expression of Birt-Hogg-Dubé gene mRNA in normal and neoplastic human tissues. Mod Pathol. 2004 Aug;17(8):998-1011.

Nickerson ML, Warren MB, Toro JR, Matrosova V, Glenn G, Turner ML, Duray P, Merino M, Choyke P, Pavlovich CP, Sharma N, Walther M, Munroe D, Hill R, Maher E, Greenberg C, Lerman MI, Linehan WM, Zbar B, Schmidt LS. Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dubé syndrome. Cancer Cell. 2002 Aug;2(2):157-64.

Furuya M, Nakatani Y. Birt-Hogg-Dube syndrome: clinicopathological features of the lung. J Clin Pathol. 2013 Mar;66(3):178-86. doi: 10.1136/jclinpath-2012-201200. Epub 2012 Dec 8. Review.

Kilincer A, Ariyurek OM, Karabulut N. Cystic lung disease in birt-hogg-dubé syndrome: a case series of three patients. Eurasian J Med. 2014 Jun;46(2):138-41. doi: 10.5152/eajm.2014.31.

Auerbach A, Roberts DH, Gangadharan SP, Kent MS. Birt-Hogg-Dubé syndrome in a patient presenting with familial spontaneous pneumothorax. Ann Thorac Surg. 2014 Jul;98(1):325-7. doi: 10.1016/j.athoracsur.2013.09.022.

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Responsible Party:	Hans Smit, MD, PhD, Free University Medical Center
ClinicalTrials.gov Identifier:	NCT02916992
Other Study ID Numbers:	2014-0525 50605 ( Registry Identifier: ABR number ) 2014-1386 ( Registry Identifier: METc ) NL50605.091.14 ( Registry Identifier: NL nummer )
First Posted:	September 28, 2016 Key Record Dates
Last Update Posted:	October 26, 2016
Last Verified:	October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by Hans Smit, Free University Medical Center:


spontaneous pneumothorax familial pneumothorax Birt-Hogg-Dube syndrome prevalence FLCN mutation Lung cysts	BHD inherited disease genetic disease primary pneumothorax CAT scan CT scan

Additional relevant MeSH terms:

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Birt-Hogg-Dube Syndrome Pneumothorax Pleural Diseases Respiratory Tract Diseases	Neoplastic Syndromes, Hereditary Neoplasms Genetic Diseases, Inborn

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