Von Hippel-Lindaus DiseaseNCT02207686
Assessment of Residual VHL Function in Tumors - Can it Predict the Patients' Individual Course of Disease?
An observational study of Von Hippel-Lindaus Disease, run by Marie Luise Bisgaard, MD at 1 site in Denmark.
Trial summary
The investigators aim to analyze tumors from vHL patients who have different courses of disease and different types of VHL gene alterations to characterize which types of genetic alterations the tumors contain and how these alterations affect the tumor cells' behavior on a molecular level. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Von Hippel-Lindaus Disease
- How many people
- 50 participants
- Where
- 1 siteDenmark
- Study dates
- Sep 2014to Aug 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: vHL patients over 18 years of age who have had at least one vHL-related tumor removed, and for whom a reference DNA sample (from blood or normal tissue) and tumor tissue (paraffin-embedded or fresh frozen) can be obtained.
Who may be able to join
- vHL diagnosed in patient
- Patient over 18 years of age
- Informed consent to participate can be obtained
- Patient has had at least one vHL-related tumor removed
- A reference DNA sample (from blood or normal tissue) and tumor tissue (paraffin-embedded or fresh frozen) can be obtained.
Who cannot join
- Patients under the age of 18 years
- Patients who had not previously had a vHL-related tumor removed
- Patients whos previously removed tumor tissue cannot be obtained or is of such a quantity or quality that no exact histological analysis can be done and/or no DNA can be extracted
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Department of Cellular and Molecular Medicine, University of Copenhagen
Copenhagen, Copenhagen N, DK-2200
About this study
The investigators aim to analyze tumors from vHL patients who have different courses of disease and different types of VHL gene alterations to characterize which types of genetic alterations the tumors contain and how these alterations affect the tumor cells' behavior on a molecular level. The investigators will then compare these observations to vHL disease outcome in patients and families.
It is already known that most vHL tumors develop when both copies of the VHL gene in a cell are inactivated. The first copy is inactivated in all the person's cells from birth ("first hit"), leaving just one functional copy. A tumor can develop from cells where the second copy is also inactivated ("second hit"). So far, only the molecular consequences of the first hit have been investigated. It is our hypothesis that both the first and second hits in combination have consequences for tumor development and clinical outcome. The investigators will include tumors from patients with different disease courses and different types of "first hits" and analyse the tumors' DNA in order to find correlations between the first and second hits and patients' and families' medical histories. The investigators hereby hope to give new insights into how vHL tumors grow and which genetic factors influence tumor development. These results will contribute to the current knowledge of vHL and help us get one step closer to be able to predict an individual's tumor risks and need for surveillance.
Read the detailed description
In vHL tumors from patients with different phenotypes and different genetic backgrounds, the investigators aim to assess both the nature of germline and somatic VHL mutations along with the total residual VHL protein (pVHL) activity in tumor cells and evaluate association to disease outcome in patients and families.
vHL tumor development follows Knudson's "two-hit-mode": patients are born with a germline mutation in one copy of their VHL gene in all the cells of the body - "the first hit". Somatic mutation in the other copy of the VHL gene - "the second hit" - initiates tumor development. Pheno-genotype correlations are well known in vHL, but have so far been explained exclusively by the nature of the germline mutation (the first hit). It is the investigators' hypothesis that it is the total residual activity of the protein (pVHL) present in the tumor after both first and second hit, which decides each tumor's destiny.
The investigators will apply Sanger sequencing, MLPA (and multiplex ligation dependent probe amplification), LOH (Loss of heterogeneity) analysis, methylation assays, FISH (Fluorescence In Situ Hybridization), and immunohistochemistry to characterize the germline and somatic mutations, determine presence of mRNA and pVHL, and assess residual VHL activity in each tumor. All these methods are already established in our laboratory.
The results will give deeper insight to vHL tumorigenesis and pave the road to future individual prediction of each patient´s course of disease and need for surveillance.
- Conditions
- Von Hippel-Lindaus Disease
- Keywords
- CNS hemangioblastoma, Renal Cell Carcinoma, VHL germline mutation, VHL somatic mutation, Tumor development
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| von Hippel-Lindau disease | Patients with von Hippel-Lindau disease who have had at least one vHL-related tumor removed |
What is being measured
The primary outcome is the main question the study is designed to answer.
Residual pVHL activity measured by amount of VHL mRNA in tumor cells
We will correlate amount of VHL mRNA in tumor cells with the type of the patients' first hit (germline mutation) and the tumor's second hits (somatic mutations).
Measured: Two years
Secondary outcomes (4)
Presence of VHL protein (pVHL) in tumor cells
We will correlated the presence of pVHL in tumor cells with the nature of the patients' (germline mutation) and the tumor cells' second hits (somatic mutations).
Measured: Two years
Type of second hit (somatic mutation) found in DNA from tumor cells
We will correlate the type of germline mutation found in the patient's DNA from blood with the types of second hits (somatic mutations) found in the tumor's DNA.
Measured: One year
Patient's age at tumor diagnosis
For each tumor we will correlate the previous outcome measures to the patient's age at tumor diagnosis
Measured: Two years
Patient's total tumor burden
For each tumor we will correlate the previous outcome measures to the patient's total tumor burden
Measured: Two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2014 (estimated)
- Study startSep 2014
- Primary completionAug 2016 (estimated)
- Study completionAug 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Von Hippel-Lindaus DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Marie Luise Bisgaard, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Marie Luise Bisgaard, MD, University of Copenhagen
- Investigators
- Marie Luise Bisgaard, MD, Principal investigator, Department of Cellular and Molecular Medicine, University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02207686
- Sponsor's protocol ID
- H-2-2010-012-A
- Status last verified
- Nov 2015
- First submitted
- 1 Aug 2014
- Last updated
- 13 Nov 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Residual VHL Function in Tumors - Can it Predict the Patients' Individual Course of Disease?
- ClinicalTrials.gov ID
- NCT02207686
- Acronym / sponsor ID
- H-2-2010-012-A
- Conditions
- Von Hippel-Lindaus Disease
- Keywords
- CNS hemangioblastoma, Renal Cell Carcinoma, VHL germline mutation, VHL somatic mutation, Tumor development
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Marie Luise Bisgaard, MDUniversity, hospital or other
- Study start
- Sep 2014
- Primary completion
- Aug 2016 (estimated)
- Study completion
- Aug 2017 (estimated)
- First posted
- 4 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators aim to analyze tumors from vHL patients who have different courses of disease and different types of VHL gene alterations to characterize which types of genetic alterations the tumors contain and how these alterations affect the tumor cells' behavior on a molecular level. The investigators will then compare these observations to vHL disease outcome in patients and families.
It is already known that most vHL tumors develop when both copies of the VHL gene in a cell are inactivated. The first copy is inactivated in all the person's cells from birth ("first hit"), leaving just one functional copy. A tumor can develop from cells where the second copy is also inactivated ("second hit"). So far, only the molecular consequences of the first hit have been investigated. It is our hypothesis that both the first and second hits in combination have consequences for tumor development and clinical outcome. The investigators will include tumors from patients with different disease courses and different types of "first hits" and analyse the tumors' DNA in order to find correlations between the first and second hits and patients' and families' medical histories. The investigators hereby hope to give new insights into how vHL tumors grow and which genetic factors influence tumor development. These results will contribute to the current knowledge of vHL and help us get one step closer to be able to predict an individual's tumor risks and need for surveillance.
Detailed description
In vHL tumors from patients with different phenotypes and different genetic backgrounds, the investigators aim to assess both the nature of germline and somatic VHL mutations along with the total residual VHL protein (pVHL) activity in tumor cells and evaluate association to disease outcome in patients and families.
vHL tumor development follows Knudson's "two-hit-mode": patients are born with a germline mutation in one copy of their VHL gene in all the cells of the body - "the first hit". Somatic mutation in the other copy of the VHL gene - "the second hit" - initiates tumor development. Pheno-genotype correlations are well known in vHL, but have so far been explained exclusively by the nature of the germline mutation (the first hit). It is the investigators' hypothesis that it is the total residual activity of the protein (pVHL) present in the tumor after both first and second hit, which decides each tumor's destiny.
The investigators will apply Sanger sequencing, MLPA (and multiplex ligation dependent probe amplification), LOH (Loss of heterogeneity) analysis, methylation assays, FISH (Fluorescence In Situ Hybridization), and immunohistochemistry to characterize the germline and somatic mutations, determine presence of mRNA and pVHL, and assess residual VHL activity in each tumor. All these methods are already established in our laboratory.
The results will give deeper insight to vHL tumorigenesis and pave the road to future individual prediction of each patient´s course of disease and need for surveillance.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| von Hippel-Lindau disease | – | –Patients with von Hippel-Lindau disease who have had at least one vHL-related tumor removed |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- vHL patients over 18 years of age who have had at least one vHL-related tumor removed, and for whom a reference DNA sample (from blood or normal tissue) and tumor tissue (paraffin-embedded or fresh frozen) can be obtained.
Key inclusion criteria (5 listed)
- vHL diagnosed in patient
- Patient over 18 years of age
- Informed consent to participate can be obtained
- Patient has had at least one vHL-related tumor removed
- A reference DNA sample (from blood or normal tissue) and tumor tissue (paraffin-embedded or fresh frozen) can be obtained.
Key exclusion criteria (3 listed)
- Patients under the age of 18 years
- Patients who had not previously had a vHL-related tumor removed
- Patients whos previously removed tumor tissue cannot be obtained or is of such a quantity or quality that no exact histological analysis can be done and/or no DNA can be extracted
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Residual pVHL activity measured by amount of VHL mRNA in tumor cells
Time frame: Two years
We will correlate amount of VHL mRNA in tumor cells with the type of the patients' first hit (germline mutation) and the tumor's second hits (somatic mutations).
4 secondary outcomes
Presence of VHL protein (pVHL) in tumor cells
Time frame: Two years
Type of second hit (somatic mutation) found in DNA from tumor cells
Time frame: One year
Patient's age at tumor diagnosis
Time frame: Two years
Patient's total tumor burden
Time frame: Two years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marie Luise Bisgaard, MD principal investigator
Department of Cellular and Molecular Medicine, University of Copenhagen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Von Hippel-Lindaus Disease, run by Marie Luise Bisgaard, MD at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Residual pVHL activity measured by amount of VHL mRNA in tumor cells (time frame: Two years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2015.