Modifying Genes in Neurofibromatosis 1

Learn more about:
Related Clinical Trial
Phase I Study to Assess the Effect of Food on the PK and Gastrointestinal Toxicity of Selumetinib in Adolescent Children With Neurofibromatosis Type 1 Related Plexiform Neurofibromas NFX-179 Topical Gel Treatment for Adults With Neurofibromatosis 1 (NF1) and Cutaneous Neurofibromas (cNF) Mechanism of Action of Transcranial Direct Current Stimulation in Neurofibromatosis Type 1 Study to Evaluate the Safety, Tolerability, PK Characteristics and Anti-tumor Activity of FCN-159 in Adult and Pediatric Participants With Neurofibromatosis Type 1 Evaluating Genetic Modifiers of Cutaneous Neurofibromas in Adults With Neurofibromatosis Type 1 Efficacy and Safety of Selumetinib in Adults With NF1 Who Have Symptomatic, Inoperable Plexiform Neurofibromas Systematically Assessing Changes in Plexiform Neurofibroma Related Disfigurement From Photographs of Subjects With Neurofibromatosis Type 1 on a Phase 2 Clinical Trial Pilot Randomized Control Trial of Telehealth Group for Improving Peer Relationships (PEERS) in NF1 Open Trial of Telehealth Group for Improving Peer Relationships (PEERS) in NF1 Identification of Pre-Malignant Lesions In Pediatric Patients With Neurofibromatosis Type 1 Using Novel Magnetic Resonance Imaging Techniques Paired With Artificial Intelligence A Study of Selumetinib in Chinese Paediatric and Adult Subjects With Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas (PN) Innovation in the Treatment of Persistent Pain in Adults With NF1: Implementation of the iCanCope Mobile Application- Clinical Trial Antioxidant Therapy With N-acetylcysteine for Children With Neurofibromatosis Type 1 Antioxidant Therapy With N-acetylcysteine for Learning and Motor Behavior in Children With Neurofibromatosis Type 1 A Long-term Study of NPC-12G Gel in Neurofibromatosis Type I NFX-179 Topical Gel Treatment in Adults With Neurofibromatosis 1 (NF1) and Cutaneous Neurofibromas (cNF) Analysis of Data Collected From Individuals Administered Neurobehavioral Assessments Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia Comparison of Gastrointestinal Motility in Healthy Children and Children With Constipation AZD6244 Hydrogen Sulfate for Children With Nervous System Tumors Photodynamic Therapy for Benign Dermal Neurofibromas- Phase II Phase II Study of Gleevec/Imatinib Mesylate (STI-571, NCS 716051) in Neurofibromatosis (NF1) Patients With Plexiform Neurofibromas Medical Treatment of “High-Risk” Neurofibromas Fludeoxyglucose F 18 Positron Emission Tomography and Magnetic Resonance Perfusion Imaging in Patients With Neurofibromatosis 1 and Plexiform Neurofibroma Whole Body MRI to Identify Atypical Neurofibromas in Patients With NF1 Use of Topical Liquid Diclofenac Following Laser Microporation of Cutaneous Neurofibromas in Patients With NF1 Development and Validation of Patient Reported Outcome (PRO) Measures for Individuals With Neurofibromatosis 1 (NF1) and Plexiform Neurofibromas (PNs) Combination Chemotherapy in Treating Patients With Neurofibromatosis and Progressive Plexiform Neurofibromas Pilot Study of Gleevec/Imatinib Mesylate (STI-571, NSC 716051) in Neurofibromatosis (NF1) Patient With Plexiform Neurofibromas Treatment of NF1-related Plexiform Neurofibroma With Trametinib Subtle Myocardial Deformation Abnormalities in Asymptomatic Nf-1 Patients R115777 to Treat Children With Neurofibromatosis Type 1 and Progressive Plexiform Neurofibromas Use of RAD001 as Monotherapy in the Treatment of Neurofibromatosis 1 Related Internal Plexiform Neurofibromas Pirfenidone in Children and Young Adults With Neurofibromatosis Type I and Progressive Plexiform Neurofibromas Study of Tasigna®/Nilotinib (AMN107) in Neurofibromatosis (NF1) Patients With Plexiform Neurofibromas Ranibizumab for Neurofibromas Associated With Neurofibromatosis 1 AZD2171 in Treating Patients With Neurofibromatosis Type 1 and Plexiform Neurofibroma and/or Neurofibroma Near the Spine MEK 1/2 Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) in Adults With Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas Study of Sutent®/Sunitinib (SU11248) in Subjects With NF-1 Plexiform Neurofibromas Neurofibromatosis Type 1 Brain Tumor Genetic Risk Acceptance and Commitment Therapy for Adolescents and Young Adults With Neurofibromatosis and Chronic Pain Phase II Study of Binimetinib in Children and Adults With NF1 Plexiform Neurofibromas Adaptation and Quality of Life Among Adults With Neurofibromatosis Type I Reliability of Functional Outcome Measures in Neurofibromatosis 1 Cabozantinib for Plexiform Neurofibromas (PN) in Subjects With NF1 in Children and Adults Medication Adherence in Children, Adolescents and Adults With Neurofibromatosis Type 1 (NF1) on Clinical Treatment Trials Targeting the Mechanisms Underlying Cutaneous Neurofibroma Formation in NF1: A Clinical Translational Approach. Sorafenib to Treat Children and Young Adults With Neurofibromatosis Type 1 and Inoperable Plexiform Neurofibromas Mitogen Activated Protein Kinase Kinase (MEK1/2) Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) in People With Neurofibromatosis Type 1 (NF1) Mutated Gastrointestinal Stromal Tumors (GIST) Quality of Friendships in Children With Neurofibromatosis Study of Disease Severity in Adults With Neurofibromatosis Type 1 (NF1) MEK Inhibitor Mirdametinib (PD-0325901) in Patients With Neurofibromatosis Type 1 Associated Plexiform Neurofibromas Interventions for Reading Disabilities in NF1 Everolimus for Treatment of Disfiguring Cutaneous Lesions in Neurofibromatosis1 CRAD001CUS232T Clinical Trial of Pirfenidone in Adult Patients With Neurofibromatosis 1 Acceptance and Commitment Training for Adolescents and Young Adults With Neurofibromatosis Type 1, Plexiform Neurofibromas, and Chronic Pain Neurobiology and Treatment of Reading Disability in NF-1 From Molecules to Cognition: Inhibitory Mechanisms in ASD and NF1 Vitamin D Supplementation for Adults With Neurofibromatosis Type 1 (NF1) Efficacy of Computerized Cognitive Training and Stimulant Medication in Neurofibromatosis Type 1 Analysis of Plasma for Diagnosis and Follow-up of Neurofibromatosis Type 1 Study About Annoucement of the Diagnosis of Neurofibromatosis 1 in de Novo Forms MicroRNAs in Patients With Neurofibromatosis Type 1 Pirfenidone in Treating Young Patients With Neurofibromatosis Type 1 and Plexiform Neurofibromas Stem Cells in NF1 Patients With Tumors of the Central Nervous System Function of the Pigment Epithelium in Patients With Type 1 Neurofibromatosis NF1-Attention: Study of Children With Neurofibromatosis Type 1 Treated by Methylphenidate Trial to Evaluate the Safety of Lovastatin in Individuals With Neurofibromatosis Type I (NF1) Internet Support Group for Parents of a Child With Neurofibromatosis Type 1 Reading Disability in Children With NF1 Multi-center Project: Spinal Abnormalities in Neurofibromatosis Type1 (NF1) Patients Functional Imaging and Reading Deficit in Children With NF1 Effects of Physical Training on Bone and Muscle Quality, Muscle Strength, and Motor Coordination in Children With NF1 Effect of Lamotrigine on Cognition in NF1 A Phase II Study of the mTOR Inhibitor Sirolimus in Neurofibromatosis Type 1 Related Plexiform Neurofibromas A Randomized Placebo-Controlled Study of Lovastatin in Children With Neurofibromatosis Type 1 Neurofibromatosis Type 1 (NF1) and Tibial Dysplasia Non-invasive Stimulation in Neurofibromatosis Type 1 Modifying Genes in Neurofibromatosis 1 Natural History and Biology of Skin Neurofibromas in Neurofibromatosis Type 1 Vision, Attention and Reading in Neurofibromatosis Type 1 (NF1) Children Neuropsychological Impairment and Quality of Life in Neurofibromatosis Type 1 Spinal Abnormalities in Neurofibromatosis Type 1 (NF1) Neurofibromatosis Type 1 Patient Registry Frameshift Peptides of Children With NF1 Prevalence of Constitutional Mismatch-repair Deficiency Among Suspected Neurofibromatosis Type 1/Legius Syndrome Children Without a Malignancy and Without a NF1 or SPRED1 Mutation How Neurofibromatosis Type 1 (NF1) Affects Schoolwork and Self-Esteem

Brief Title

Modifying Genes in Neurofibromatosis 1

Official Title

Study of the Neurofibromatosis 1 Expression: Identification of the Modifying Genes

Brief 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). 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 Type

Observational


Primary Outcome

Identification of the genetic variants involved in variability of clinical expression of neurofibromatosis 1.


Condition

Neurofibromatosis 1

Intervention

No intervention

Study Arms / Comparison Groups

 NF1GeneModif Cohort
Description:  Adult patients with neurofibromatosis 1

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Other

Estimated Enrollment

450

Start Date

May 2012

Completion Date

September 2015

Primary Completion Date

September 2015

Eligibility Criteria

        Inclusion Criteria:

          -  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

          -  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.

        Exclusion Criteria:

          -  Children (< 18 year-old)

          -  One member of the family already included in the study
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Pierre Wolkenstein, MD, PhD, , 

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT01650142

Organization ID

AOM 10 005

Secondary IDs

2010-023137-34

Responsible Party

Sponsor

Study Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

 French National Referral Center for Neurofibromatoses

Study Sponsor

Pierre Wolkenstein, MD, PhD, Principal Investigator, Assistance Publique - Hôpitaux de Paris


Verification Date

June 2014