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Genetic Analysis of Birt Hogg-Dube Syndrome and Characterization of Predisposition to Kidney Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00033137
Recruitment Status : Recruiting
First Posted : April 8, 2002
Last Update Posted : February 20, 2020
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

This study will investigate the genetic cause of Birt Hogg-Dube (BHD) syndrome and the relationship of this disorder to kidney cancer. BHD is a rare inherited condition characterized by papules, or bumps benign tumors involving hair follicles on the head and neck. People with BHD are at increased risk of developing kidney cancer. Scientists have identified the chromosome (strand of genetic material in the cell nucleus) that contains the BHD gene and the region of the gene on the chromosome. This study will try to learn more about:

  • The characteristics and type of kidney tumors associated with BHD
  • The risk of kidney cancer in people with BHD
  • Whether more than one gene causes BHD
  • The genetic mutations (changes) responsible for BHD

Patients with known or suspected Birt Hogg-Dube syndrome, and their family members, may be eligible for this study. Candidates will be screened with a family history and review of medical records, including pathology reports for tumors, and films of computed tomography (CT) and magnetic resonance imaging (MRI) scans.

Participants may undergo various tests and procedures, including the following:

  • Physical examination
  • Review of personal and family history with a cancer doctor, cancer nurses, kidney surgeon, and genetic counselor
  • Chest and other x-rays
  • Ultrasound (imaging study using sound waves)
  • MRI (imaging study using radiowaves and a magnetic field)
  • CT scans of the chest and abdomen (imaging studies using radiation)
  • Blood tests for blood chemistries and genetic testing
  • Skin evaluation, including a skin biopsy (surgical removal of a small skin tissue sample for microscopic evaluation)
  • Cheek swab or mouthwash to collect cells for genetic analysis
  • Lung function studies
  • Medical photography of skin lesions

These tests will be done on an outpatient basis in either one day or over 3 to 4 days. When the studies are complete, participants will receive counseling about the findings and recommendations. Patients with kidney lesions may be asked to return periodically, such as every 3 to 36 months, based on their individual condition, to document the rate of progression of the lesions.

...


Condition or disease
Kidney Neoplasms Kidney Cancer Pneumothorax FLCN Protien, Human

Detailed Description:

Background:

  • BHD is a rare, autosomal dominantly inherited disorder which confers susceptibility to develop multifocal, bilateral renal cancer, spontaneous pneumothorax and fibrofolliculomas.
  • BHD is caused by mutations in the BHD gene located on Chromosome17
  • Defining the genetic and biochemical pathways leading to renal tumorigenesis in BHD may lead to the development of new molecularly targeted drugs.

Objectives:

  • To define the types and characteristics (including patterns of growth) of renal cancer associated with BHD
  • To determine the risk of renal cancer, lung cysts and fibrofolliculomas in patients with BHD
  • To define the natural history of BHD related renal tumors
  • To determine if other genes contribute to BHD
  • Identify genotype / phenotype correlations

Eligibility:

  • Patients with phenotype or genotype suggestive of Birt Hogg Dube, such as:

    • Patients with histologically confirmed fibrofolliculomas,
    • Patients with clinical evidence of multiple skin papules consistent with fibrofolliculomas, and a family history of spontaneous pneumothorax or kidney cancer
  • A relative (related by blood or marriage) of a patient with a confirmed or suspected diagnosis of BHD
  • Patients with a known germline BHD mutation

Design:

  • These rare families will be recruited to genetically confirm diagnosis, determine size and location of renal tumors, size at presentation, growth rate and metastatic potential of renal tumors.
  • Genetic testing will be offered to gain appreciation of the effect of mutations the BHD gene and to assess the relative activity of various germline and somatic mutations.
  • We will determine if there is a relationship between mutation and disease phenotype.

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Study Type : Observational
Estimated Enrollment : 800 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Birt Hogg-Dube Syndrome: Identification of the Disease Gene and Characterization of the Predisposition of Renal Cancer
Actual Study Start Date : May 13, 2002


Group/Cohort
Family members
A relative of a patient with a confirmed or suspected diagnosis of BHD (related by blood or marriage)
Patients
Patients with phenotype or genotype suggestive of Birt Hogg Dub(SqrRoot)(Copyright) and/or Renal tumor histology consistent with BHD



Primary Outcome Measures :
  1. Define types and characteristics (including patterns of growth) of renal cancer associated with BHD. [ Time Frame: Ongoing ]
    Collection of blood, tissue & urine for Identification of the Disease Gene, and Characterization of the disposition to Renal Cancer

  2. Determine risk of renal cancer, lung cysts and fibrofollicullomas in patients with BHD. [ Time Frame: Ongoing ]
    Collection of blood, tissue & urine for Identification of the Disease Gene, and Characterization of the disposition to Renal Cancer

  3. Define the natural history of BHD related renal tumors. [ Time Frame: Ongoing ]
    Collection of blood, tissue & urine for Identification of the Disease Gene, and Characterization of the disposition to Renal Cancer

  4. Determine if other genes contribute to BHD. [ Time Frame: Ongoing ]
    Collection of blood, tissue & urine for Identification of the Disease Gene, and Characterization of the disposition to Renal Cancer

  5. Identify genotype / phenotype correlations. [ Time Frame: Ongoing ]
    Collection of blood, tissue & urine for Identification of the Disease Gene, and Characterization of the disposition to Renal Cancer



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Patients with histologically confirmed fibrofolliculomas, Patients with clinical evidence of multiple skin papules consistent with fibrofolliculomas, and a family history of spontaneous pneumothorax or kidney cancer, a relative of a patient with a confirmed diagnosis of BHD.cPatients with a known germline BHD mutation@@@@@@
Criteria

-INCLUSION CRITERIA:

  1. Patients with phenotype or genotype suggestive of Birt Hogg Dub(SqrRoot)(Copyright), such as:

    • Patients with at least one histologically confirmed fibrofolliculomas, or
    • Patients with clinical evidence of multiple skin papules (without fibrofolliculoma biopsy confirmation) and a personal or family history of spontaneous pneumothorax / or kidney cancer, or
    • Patients with spontaneous pneumothorax and skin papules or kidney cancer and a positive family history of spontaneous pneumothorax, skin papules or kidney cancer
  2. Renal tumor histology consistent with BHD, including, but not limited to those suggestive of chromophobe, oncocytic neoplasm or oncocytoma.
  3. All patients and guardians, for children younger than 18 years of age, must sign an informed consent document indicating their understanding of the investigational nature and the risks of this study before any protocol related studies are performed. Patients

    under the age of 18 but who are age 13 or older will be asked to sign an assent document prior to participation.

  4. A relative (related by blood or marriage*) of a patient with a confirmed or suspected diagnosis of BHD. *This includes non-blood related individuals who had children but were never legally married. This excludes family members related by marriage that have since divorced, if they did not have children.

EXCLUSION CRITERIA:

NONE


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): NCT00033137


Contacts
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Contact: W. Marston Linehan, M.D. (240) 858-3700 wl3e@nih.gov

Locations
Layout table for location information
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    (888) NCI-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: W. Marston Linehan, M.D. National Cancer Institute (NCI)

Additional Information:
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00033137    
Obsolete Identifiers: NCT00039533
Other Study ID Numbers: 020159
02-C-0159
First Posted: April 8, 2002    Key Record Dates
Last Update Posted: February 20, 2020
Last Verified: January 28, 2020
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Pneumothorax
Kidney
Fibrofolliculoma
BHD
Neoplasms
Additional relevant MeSH terms:
Layout table for MeSH terms
Birt-Hogg-Dube Syndrome
Kidney Neoplasms
Carcinoma, Renal Cell
Pneumothorax
Disease Susceptibility
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Pleural Diseases
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes
Neoplastic Syndromes, Hereditary
Genetic Diseases, Inborn