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Screening for Endolymphatic Sac Tumours (ELSTs) in Von Hippel-Lindau (vHL) Patients

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ClinicalTrials.gov Identifier: NCT02420067
Recruitment Status : Recruiting
First Posted : April 17, 2015
Last Update Posted : May 9, 2017
Sponsor:
Collaborators:
Rigshospitalet, Denmark
St Thomas' Hospital, London
Fundación Hospital de Madrid
National Cancer Centre, Singapore
Yokosuka City Shimin Hospital
Amrita Institute of Medical Sciences & Research Center
Information provided by (Responsible Party):
Marie Luise Bisgaard, MD, University of Copenhagen

Brief Summary:

The purpose of the study is to investigate how best to screen for Endolymphatic sac tumors (ELSTs) in von Hippel-Lindau (vHL) patients in order to diagnose the ELSTs while they are still small so that hearing loss can be prevented.

Up to 16% of vHL patients are known to develop endolymphatic sac tumors in the inner ear that can cause permanent hearing loss. However, the ELSTs are often not found before hearing loss has already occurred. The challenge for doctors is to diagnose the ELSTs at early stages before they cause often irreversible deafness. In order to find ELSTs before they cause hearing loss, it is important to screen for the tumors prophylactically, that is screen all vHL patients regardless of whether or not they have symptoms.

Who can join? Persons diagnosed with vHL who are at least 15 years old. The investigators include patients WITH OR WITHOUT a diagnosed ELST.

What does it involve? You need to have a hearing test and an MRI of the brain, where the inner ear can be seen, most vHL patients have already had this done as part of their surveillance program.

Participants will be asked to participate in follow up examinations (hearing test and/or MRI of the brain) after 2, 5, and 10 years.

How can I join? A doctor has to be responsible for the study in each country where vHL patients participates.

Ask the doctor who manages your vHL examinations to contact us or contact us yourself and the investigators will help you find a doctor in your country who will participate in the study.


Condition or disease
Von Hippel-Lindau Disease

  Show Detailed Description

Study Type : Observational
Estimated Enrollment : 380 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: An International Collaborative Study: Screening for Endolymphatic Sac Tumours (ELSTs) in Von Hippel-Lindau (vHL) Patients
Study Start Date : February 2011
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : December 2026





Primary Outcome Measures :
  1. In each ear: development of an ELST during the study period correlated to baseline hearing level. [ Time Frame: Change in status of ELST diagnosis from during the ten year period from study baseline to study end. ]
    Presence and size of an ELST as diagnosed by an MRI at any time during the study period correlated to the baseline hearing level in the ear as defined by hearing level in decibel in air- and bone conduction at predefined frequencies 125, 250, 500, 1000, 2000, 4000, 8000 Hz measured with pure-tone audiometry.


Secondary Outcome Measures :
  1. In each ear: development of an ELST during the study period correlated to hearing level at two year follow-up. [ Time Frame: Change in status of ELST diagnosis from during the 8 year period from two year follow-up to study end. ]
    Presence and size of an ELST as diagnosed by an MRI at any time during the study period correlated to the hearing level at the two year follow-up in the ear as defined by hearing level in decibel in air- and bone conduction at predefined frequencies 125, 250, 500, 1000, 2000, 4000, 8000 Hz measured with pure-tone audiometry.

  2. In each ear: development of an ELST during the study period correlated to hearing level at five year follow-up. [ Time Frame: Change in status of ELST diagnosis from during the 5 year period from five year follow-up to study end. ]
    Presence and size of an ELST as diagnosed by an MRI at any time during the study period correlated to the hearing level at the five year follow-up in the ear as defined by hearing level in decibel in air- and bone conduction at predefined frequencies 125, 250, 500, 1000, 2000, 4000, 8000 Hz measured with pure-tone audiometry.

  3. In each ear: development of an ELST during the study period correlated to presence of low-frequency hearing loss (sensorineural) pattern A at baseline assessment. [ Time Frame: Change in status of ELST diagnosis during the 10 year period from study initiation to study end. ]
    Presence and size of an ELST as diagnosed by an MRI at any time during the study period correlated to presence of low-frequency hearing loss (sensorineural) type A as defined by (Th500 Hz - Th1.000 Hz > 5 dB) AND (Th250 Hz > Th1.000 Hz) measured during a pure-tone audiometry at baseline assessment.

  4. In each ear: development of an ELST during the study period correlated to presence of low-frequency hearing loss (sensorineural) pattern A at the two-year follow-up assessment.. [ Time Frame: Change in status of ELST diagnosis during the 8 year period from study initiation to the two-year follow-up assessment. ]
    Presence and size of an ELST as diagnosed by an MRI at any time during the study period correlated to presence of low-frequency hearing loss (sensorineural) type A as defined by (Th500 Hz - Th1.000 Hz > 5 dB) AND (Th250 Hz > Th1.000 Hz) measured during a pure-tone audiometry at two-year follow-up assessment.

  5. In each ear: development of an ELST during the study period correlated to presence of low-frequency hearing loss (sensorineural) pattern A at the five-year follow-up assessment. [ Time Frame: Change in status of ELST diagnosis during the 5 year period from study initiation to the five-year follow-up assessment. ]
    Presence and size of an ELST as diagnosed by an MRI at any time during the study period correlated to presence of low-frequency hearing loss (sensorineural) type A as defined by (Th500 Hz - Th1.000 Hz > 5 dB) AND (Th250 Hz > Th1.000 Hz) measured during a pure-tone audiometry at five-year follow-up assessment.

  6. In each ear: development of an ELST during the study period correlated to presence of low-frequency hearing loss (sensorineural) pattern B at baseline assessment. [ Time Frame: Change in status of ELST diagnosis during the 10 year period from study initiation to study end. ]
    Presence and size of an ELST as diagnosed by an MRI at any time during the study period correlated to presence of low-frequency hearing loss (sensorineural) type B as defined by (Th1.000 Hz > Th2.000 Hz) and (Th500 - Th2.000 Hz > 9 dB) and (Th250 Hz -2.000 H< > 9 dB) measured during a pure-tone audiometry at baseline assessment.

  7. In each ear: development of an ELST during the study period correlated to presence of low-frequency hearing loss (sensorineural) pattern B at the two-year follow-up assessment. [ Time Frame: Change in status of ELST diagnosis during the 8 year period from study initiation to the two-year follow-up assessment. ]
    Presence and size of an ELST as diagnosed by an MRI at any time during the study period correlated to presence of low-frequency hearing loss (sensorineural) type B as defined by (Th1.000 Hz > Th2.000 Hz) and (Th500 - Th2.000 Hz > 9 dB) and (Th250 Hz -2.000 H< > 9 dB) measured during a pure-tone audiometry at the two-year follow-up assessment.

  8. In each ear: development of an ELST during the study period correlated to presence of low-frequency hearing loss (sensorineural) pattern B at the five-year follow-up assessment. [ Time Frame: Change in status of ELST diagnosis during the 5 year period from study initiation to the five-year follow-up assessment. ]
    Presence and size of an ELST as diagnosed by an MRI at any time during the study period correlated to presence of low-frequency hearing loss (sensorineural) type B as defined by (Th1.000 Hz > Th2.000 Hz) and (Th500 - Th2.000 Hz > 9 dB) and (Th250 Hz -2.000 H< > 9 dB) measured during a pure-tone audiometry at the five-year follow-up assessment.

  9. Development of an ELST during the study period correlated to presence of subjective audio-vestibular symptoms at the baseline assessment. [ Time Frame: Change in status of ELST diagnosis during the 10 year period from study initiation to the study end. ]
    Presence and size of an ELST as diagnosed by an MRI at any time during the study period correlated to presence of audio-vestibular symptoms in the form of hearing loss, tinnitus, vertigo, sense of aural fullness, and ear pain that are not known to have an non-ELST cause as reported by the patient at the baseline assessment.

  10. Development of an ELST during the study period correlated to presence of subjective audio-vestibular symptoms at the two-year follow-up assessment. [ Time Frame: Change in status of ELST diagnosis during the 8 year period from study initiation to the two-year follow-up assessment. ]
    Presence and size of an ELST as diagnosed by an MRI at any time during the study period correlated to presence of audio-vestibular symptoms in the form of hearing loss, tinnitus, vertigo, sense of aural fullness, and ear pain that are not known to have an non-ELST cause as reported by the patient at the two-year follow-up assessment.

  11. Development of an ELST during the study period correlated to presence of subjective audio-vestibular symptoms at the five-year follow-up assessment. [ Time Frame: Change in status of ELST diagnosis during the 5 year period from study initiation to the five-year follow-up assessment. ]
    Presence and size of an ELST as diagnosed by an MRI at any time during the study period correlated to presence of audio-vestibular symptoms in the form of hearing loss, tinnitus, vertigo, sense of aural fullness, and ear pain that are not known to have an non-ELST cause as reported by the patient at the five-year follow-up assessment.


Other Outcome Measures:
  1. VHL mutation status related to presence of hearing loss and/or presence of ELST at any time during the study. [ Time Frame: Assessed at the end of the study ten year after study initiation. ]
    Presence of a VHL mutation confirmed by molecular analysis correlated to hearing loss as determined during audiometry and/or to presence of an ELST as diagnosed by MRI during the study.

  2. Type of VHL mutation related to presence of hearing loss and/or presence of ELST at any time during the study. [ Time Frame: Assessed at the end of the study ten year after study initiation ]
    Type of a VHL mutation confirmed by molecular analysis (mutations predicted to truncate the protein product or not) correlated to hearing loss as determined during audiometry and/or to presence of an ELST as diagnosed by MRI during the study.

  3. Type of clinical vHL type related to presence of hearing loss and/or presence of ELST at any time during the study. [ Time Frame: Assessed at the end of the study ten year after study initiation ]
    Type of clinical vHL type as defined by previously diagnosis of other types of vHL-related manifestations in the patient (cerebellar hemangioblastomas, retinal hemangioblastoma, renal cell carcinoma, renal cysts, pancreatic tumors, pancreatic cysts, pheochromocytomas, paragangliomas, Epidydydimal cysts/ cysts of the broad uterine ligament) correlated to hearing loss as determined during audiometry and/or to presence of an ELST as diagnosed by MRI during the study.



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Ages Eligible for Study:   15 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
vHL patients, with or without a diagnosed ELST, who have had at least one audiological examination AND one MRI of the brain and inner ear within a 12 month period
Criteria

Inclusion Criteria:

  • A diagnosis of vHL (either a carrier of a VHL mutation or vHL diagnosed by clinical criteria, i.e. at least two vHL-related manifestations diagnosed or one vHL-related manifestation diagnosed AND a first-degree relative with vHL)
  • At least one audiological examination (including an audiogramme) and one MRI examination of the brain also visualizing the inner ear within 12 months of each other

Exclusion Criteria:

  • Children under the age of 15 years

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): NCT02420067


Contacts
Contact: Marie Luise Bisgaard, M.D. 004531333582 mlbi@sund.ku.dk
Contact: Marie Louise M Binderup, M.D. 004526363991 mlmb@sund.ku.dk

Locations
Denmark
Department of Cellular and Molecular Medicine, University of Copenhagen Recruiting
Copenhagen, Copenhagen N, Denmark, DK-2200
Contact: Marie Louise M Binderup, M.D.    004526363991    mlmb@sund.ku.dk   
Principal Investigator: Marie Luise Bisgaard, MD         
Sub-Investigator: Marie Louise Binderup, MD         
Sponsors and Collaborators
Marie Luise Bisgaard, MD
Rigshospitalet, Denmark
St Thomas' Hospital, London
Fundación Hospital de Madrid
National Cancer Centre, Singapore
Yokosuka City Shimin Hospital
Amrita Institute of Medical Sciences & Research Center
Investigators
Principal Investigator: Marie Luise Bisgaard, M.D. Department of Cellular and Molecular Medicin, University of Copenhagen

Additional Information:
Responsible Party: Marie Luise Bisgaard, MD, Associate Professor, University of Copenhagen
ClinicalTrials.gov Identifier: NCT02420067     History of Changes
Other Study ID Numbers: H-A-2007-0125, A
First Posted: April 17, 2015    Key Record Dates
Last Update Posted: May 9, 2017
Last Verified: May 2017

Keywords provided by Marie Luise Bisgaard, MD, University of Copenhagen:
von Hippel-Lindau disease
Endolymphatic sac tumors
Audiological examination
MRI
Surveillance

Additional relevant MeSH terms:
Von Hippel-Lindau Disease
Neurocutaneous Syndromes
Nervous System Diseases
Angiomatosis
Vascular Diseases
Cardiovascular Diseases