Prevalence of Spontaneous Pneumothorax in BHD

Spontaneous Pneumothorax Clinical Trial

Official title:

Prevalence of Birt-Hogg-Dubé Syndrome Among Patients With (Hereditary) Spontaneous Pneumothorax

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02916992
• Other study ID #: 2014-0525
• Secondary ID: 506052014-1386NL
• Status: Recruiting
• Phase: Phase 1
• First received: January 23, 2016
• Last updated: October 24, 2016
• Start date: September 2016
• Est. completion date: July 2017

Study information

• Verified date: October 2016
• Source: Free University Medical Center
• Contact: Jincey D. Sriram, MD, MSc
• Phone: 0880058888
• Email: JSriram[@]Rijnstate.nl
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: July 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• treated in Rijnstate hospital for primary spontaneous pneumothorax

• informed consent

Exclusion Criteria:

• secondary or iatrogenic pneumothorax

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Screening

Related Conditions & MeSH terms

• Birt-Hogg-Dube Syndrome
• Pneumothorax
• Spontaneous Pneumothorax

Intervention

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.

Locations

Country	Name	City	State
Netherlands	Rijnstate	Arnhem	Gelderland

Sponsors (4)

Lead Sponsor	Collaborator
Hans Smit	Mr. Willem Bakhuys Roozeboomstichting, Prof. Dr. Jaap Swieringa stichting, Rijnstate Hospital

Country where clinical trial is conducted

Netherlands, 

References & Publications (12)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	presence of pathogenic FLCN mutations	by assessing blood samples	6 months	No
Secondary	presence of lung cysts	visible on pulmonary low dose CT	6 months	No

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