Neurofibromatosis 1NFGENMODIFNCT01650142
Modifying Genes in Neurofibromatosis 1
An observational study of Neurofibromatosis 1, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Thanks to the investigators previous study the investigators demonstrated the influence of modifying genes in the phenotypic expression of neurofibromatosis 1 (Hum Mol Genet. 2009; 18 (15) :2768-78). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neurofibromatosis 1
- How many people
- 450 participants
- Where
- 1 siteFrance
- Study dates
- May 2012to Sep 2015
- 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: Adult patients with neurofibromatosis 1 according to the NIH criteria followed in NF France network, a national network devoted in to neurofibromatosis 1
Who may be able to join
- Aged of 18 or more
- Patient with neurofibromatosis 1 according the NIH criteria :
- Six or more café au lait macules over 15 mm in greatest diameter in postpubertal individuals
- Two or more neurofibromas of any type or one plexiform neurofibroma
- Freckling in the axillary or inguinal regions (Crowe´s sign)
- Optic glioma
Show all 10Show fewer
- Two or more Lisch nodules (iris hamartomas)
- A distinctive osseous lesion such as sphenoid dysplasia or thinning of long bone cortex with or without pseudoarthrosis
- A first-degree relative (parent, sibling, or offspring) with NF1 by the above criteria
- The criteria are met in an individual if two or more of the features listed are present.
Who cannot join
- Children (< 18 year-old)
- One member of the family already included in the study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Study of the Neurofibromatosis 1 Expression: Identification of the Modifying Genes
Thanks to the investigators previous study the investigators demonstrated the influence of modifying genes in the phenotypic expression of neurofibromatosis 1 (Hum Mol Genet. 2009; 18 (15) :2768-78). Indeed, analysis of the intra-and inter-family variability performed using the investigators phenotype/genotype database demonstrated a strong genetic component for most clinical features. The investigators results suggest the involvement of genetic factors, not related to the NF1 gene, the modifiers. The objective of this project is to identify the modifiers involved in the variability of clinical expression of NF1. The investigators will focus in particular variants involved in the development and progression of neurofibromas.
Read the detailed description
Neurofibromatosis 1(NF1) is a rare autosomal dominant disorder with an incidence of one birth out of 3000. NF1 gene is located in 17q11.2. The penetrance is near 100% by the age of 8 and the de novo mutations represent half the cases. The product of NF1 gene is neurofibromin, a protein controlling cellular differentiation and proliferation. Phenotypic expression is variable even in the same family. Neurofibromatosis 1 is characterized by café au lait spots, freckling of the folds, Lisch'nodules (hamartomas of iris) and multiple neurofibromas. Manifestations of neurofibromatosis 1 are pleiotropic, potentially severe and unpredictable. Morbidity and mortality associated to neurofibromatosis 1 are linked with complications, optic pathway gliomas, neurofibromas of the spine or of peripheral nerves, learning disabilities, scoliosis and bone abnormalities and vasculopathy. The investigators already demonstrated the existence of modifiers, genes modifying the phenotypic expression of neurofibromatosis 1 (Hum Mol Genet. 2009;18(15):2768-78). Indeed, a quantitative analysis of inter and intrafamilial variability performed with the data of the investigators phenotype/genotype database showed a strong genetic component for most studied clinical traits with an estimated heritability from 44 and 45% for subcutaneous and plexiform neurofibromas, to 66% for small café au lait spots. The investigators also showed that the NF1 gene had minor effect in the phenotypic variability. The investigators results suggested the implication of genes non linked to NF1 gene. The identification of these variants called modifiers of the phenotype is possible thanks to the investigators vast collection of patients and its statistical power. The aim of the present study is to identify in the human genome genetic variants in the evolving pattern of the most frequent manifestation of neurofibromatosis 1, neurofibromas. The genetic association studies are the most adapted in that purpose. The investigators bank includes at the present time 1099 patients of 575 families with genotypes, phenotypes and DNA samples.
The investigators will include 450 index cases more to have around 1000 independent patients with neurofibromatosis 1 to get a 90% statistical power to detect variants of 30% frequency in the general population and having an effect of odds ratio of 2 for studied trait. The investigators will use Affymetrix® Genechips 6.0 covering well the whole genome.
Identification of the variants will provide new comprehension of pathophysiology and new targets for treatment.
- Conditions
- Neurofibromatosis 1
- Being tested
- No intervention
- Keywords
- Neurofibromatosis 1, Phenotype, Modifiers
- Medical subject headings
- Neurofibromatosis 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No interventionOther
No intervention
| Study group | Role | What they receive |
|---|---|---|
| NF1GeneModif Cohort | Adult patients with neurofibromatosis 1 Receives: Other: No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of the genetic variants involved in variability of clinical expression of neurofibromatosis 1.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2012 (estimated)
- Study startMay 2012
- Primary completionSep 2015 (estimated)
- Study completionSep 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Neurofibromatosis 1Studies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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
- Prospective
- Enrolment
- 450 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- French National Referral Center for Neurofibromatoses
- Responsible party
- Sponsor
- Investigators
- Pierre Wolkenstein, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01650142
- Sponsor's protocol ID
- AOM 10 005
- Other IDs
- 2010-023137-34
- Acronym
- NFGENMODIF
- Status last verified
- Jun 2014
- First submitted
- 29 May 2012
- Last updated
- 16 Jun 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Easton DF, Ponder MA, Huson SM, Ponder BA. An analysis of variation in expression of neurofibromatosis (NF) type 1 (NF1): evidence for modifying genes. Am J Hum Genet. 1993 Aug;53(2):305-13.
PubMed 8328449Gutmann DH, Aylsworth A, Carey JC, Korf B, Marks J, Pyeritz RE, Rubenstein A, Viskochil D. The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA. 1997 Jul 2;278(1):51-7.
PubMed 9207339Sabbagh A, Pasmant E, Laurendeau I, Parfait B, Barbarot S, Guillot B, Combemale P, Ferkal S, Vidaud M, Aubourg P, Vidaud D, Wolkenstein P; members of the NF France Network. Unravelling the genetic basis of variable clinical expression in neurofibromatosis 1. Hum Mol Genet. 2009 Aug 1;18(15):2768-78. doi: 10.1093/hmg/ddp212. Epub 2009 May 5.
PubMed 19417008
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Neurofibromatosis 1 Expression: Identification of the Modifying Genes
- ClinicalTrials.gov ID
- NCT01650142
- Acronym / sponsor ID
- NFGENMODIF / AOM 10 005
- Conditions
- Neurofibromatosis 1
- Keywords
- Neurofibromatosis 1, Phenotype, Modifiers
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 450 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- French National Referral Center for Neurofibromatoses
- Study start
- May 2012
- Primary completion
- Sep 2015 (estimated)
- Study completion
- Sep 2015 (estimated)
- First posted
- 26 Jul 2012 (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.
Thanks to the investigators previous study the investigators demonstrated the influence of modifying genes in the phenotypic expression of neurofibromatosis 1 (Hum Mol Genet. 2009; 18 (15) :2768-78). Indeed, analysis of the intra-and inter-family variability performed using the investigators phenotype/genotype database demonstrated a strong genetic component for most clinical features. The investigators results suggest the involvement of genetic factors, not related to the NF1 gene, the modifiers. The objective of this project is to identify the modifiers involved in the variability of clinical expression of NF1. The investigators will focus in particular variants involved in the development and progression of neurofibromas.
Detailed description
Neurofibromatosis 1(NF1) is a rare autosomal dominant disorder with an incidence of one birth out of 3000. NF1 gene is located in 17q11.2. The penetrance is near 100% by the age of 8 and the de novo mutations represent half the cases. The product of NF1 gene is neurofibromin, a protein controlling cellular differentiation and proliferation. Phenotypic expression is variable even in the same family. Neurofibromatosis 1 is characterized by café au lait spots, freckling of the folds, Lisch'nodules (hamartomas of iris) and multiple neurofibromas. Manifestations of neurofibromatosis 1 are pleiotropic, potentially severe and unpredictable. Morbidity and mortality associated to neurofibromatosis 1 are linked with complications, optic pathway gliomas, neurofibromas of the spine or of peripheral nerves, learning disabilities, scoliosis and bone abnormalities and vasculopathy. The investigators already demonstrated the existence of modifiers, genes modifying the phenotypic expression of neurofibromatosis 1 (Hum Mol Genet. 2009;18(15):2768-78). Indeed, a quantitative analysis of inter and intrafamilial variability performed with the data of the investigators phenotype/genotype database showed a strong genetic component for most studied clinical traits with an estimated heritability from 44 and 45% for subcutaneous and plexiform neurofibromas, to 66% for small café au lait spots. The investigators also showed that the NF1 gene had minor effect in the phenotypic variability. The investigators results suggested the implication of genes non linked to NF1 gene. The identification of these variants called modifiers of the phenotype is possible thanks to the investigators vast collection of patients and its statistical power. The aim of the present study is to identify in the human genome genetic variants in the evolving pattern of the most frequent manifestation of neurofibromatosis 1, neurofibromas. The genetic association studies are the most adapted in that purpose. The investigators bank includes at the present time 1099 patients of 575 families with genotypes, phenotypes and DNA samples.
The investigators will include 450 index cases more to have around 1000 independent patients with neurofibromatosis 1 to get a 90% statistical power to detect variants of 30% frequency in the general population and having an effect of odds ratio of 2 for studied trait. The investigators will use Affymetrix® Genechips 6.0 covering well the whole genome.
Identification of the variants will provide new comprehension of pathophysiology and new targets for treatment.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NF1GeneModif Cohort | – | Other: No interventionAdult patients with neurofibromatosis 1 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adult patients with neurofibromatosis 1 according to the NIH criteria followed in NF France network, a national network devoted in to neurofibromatosis 1
Key inclusion criteria (10 listed)
- Aged of 18 or more
- Patient with neurofibromatosis 1 according the NIH criteria :
- Six or more café au lait macules over 15 mm in greatest diameter in postpubertal individuals
- Two or more neurofibromas of any type or one plexiform neurofibroma
- Freckling in the axillary or inguinal regions (Crowe´s sign)
Key exclusion criteria (2 listed)
- Children (< 18 year-old)
- One member of the family already included in the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| No interventionNo intervention | Other | NF1GeneModif Cohort |
Primary outcome
Identification of the genetic variants involved in variability of clinical expression of neurofibromatosis 1.
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2014.
- Background: PubMed 8328449Easton DF, Ponder MA, Huson SM, Ponder BA. An analysis of variation in expression of neurofibromatosis (NF) type 1 (NF1): evidence for modifying genes. Am J Hum Genet. 1993 Aug;53(2):305-13.
- Background: PubMed 9207339Gutmann DH, Aylsworth A, Carey JC, Korf B, Marks J, Pyeritz RE, Rubenstein A, Viskochil D. The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. JAMA. 1997 Jul 2;278(1):51-7.
- Background: PubMed 19417008Sabbagh A, Pasmant E, Laurendeau I, Parfait B, Barbarot S, Guillot B, Combemale P, Ferkal S, Vidaud M, Aubourg P, Vidaud D, Wolkenstein P; members of the NF France Network. Unravelling the genetic basis of variable clinical expression in neurofibromatosis 1. Hum Mol Genet. 2009 Aug 1;18(15):2768-78. doi: 10.1093/hmg/ddp212. Epub 2009 May 5.
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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.
Pierre Wolkenstein, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
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 Neurofibromatosis 1, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 10 inclusion and 2 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 16 Jun 2014. 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 France. 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?
Identification of the genetic variants involved in variability of clinical expression of neurofibromatosis 1. (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01650142, which also lists 3 linked publications.
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 16 Jun 2014.