Studies in Patients With Tuberous Sclerosis Complex

Learn more about:
Related Clinical Trial
Doxycycline In Lymphangioleiomyomatosis (LAM) Effect of Fasting on the Size of Abdominal Lymphatic Tumors in Women Turmeric as Treatment in Epilepsy Study of the Disease Process of Lymphangioleiomyomatosis RAD001 Therapy of Angiomyolipomata in Patients With TS Complex and Sporadic LAM The Effectiveness and Safety of Vagus Nerve Stimulation for TRE The Effectiveness and Safety of Resective Epilepsy Surgery for TRE Roll-over Study to Collect and Assess Long-term Safety of Everolimus in Patients With TSC and Refractory Seizures Who Have Completed the EXIST-3 Study [CRAD001M2304] and Who Are Benefitting From Continued Treatment Adjunctive Ganaxolone Treatment (Part A) in TSC Followed by Long-term Treatment (Part B) Safety of Simvastatin in LAM and TSC Studies of Autistic Patients: Gene Networks and Clinical Subtypes Topical Rapamycin to Erase Angiofibromas in TSC Rapalogues for Autism Phenotype in TSC: A Feasibility Study A Pilot Study To Evaluate The Effects of Everolimus on Brain mTOR Activity and Cortical Hyperexcitability in TSC and FCD Everolimus for Cancer With TSC1 or TSC2 Mutation Topical Sirolimus Ointment for Cutaneous Angiofibromas in Subjects With Tuberous Sclerosis Complex The Cognitive Variability in NF1 and TSC Monozygotic Twins Long-term Trial of Topical Sirolimus to Angiofibroma in Patient With Tuberous Sclerosis Complex Efficacy of RAD001/Everolimus in Autism and NeuroPsychological Deficits in Children With Tuberous Sclerosis Complex Phase III Trial of Topical Formulation of Sirolimus to Skin Lesions in Patients With Tuberous Sclerosis Complex (TSC) Topical Rapamycin Therapy to Alleviate Cutaneous Manifestations of Tuberous Sclerosis Complex (TSC) and Neurofibromatosis I (NF1) Trial of Efficacy and Safety of Sirolimus in Tuberous Sclerosis and LAM Long-term, Prospective Study Evaluating Clinical and Molecular Biomarkers of Epileptogenesis in a Genetic Model of Epilepsy – Tuberous Sclerosis Complex A Randomized Controlled Trial of Cannabidiol (GWP42003-P, CBD) for Seizures in Tuberous Sclerosis Complex (GWPCARE6) An Open-label Extension Trial of Cannabidiol (GWP42003-P, CBD) for Seizures in Tuberous Sclerosis Complex (GWPCARE6) Aspirin as an add-on Treatment of Refractory Epilepsy in Tuberous Sclerosis Complex Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC) Clinical Presentation and Renal Outcome of Patients With Tuberous Sclerosis Complex and/or Renal Angiomyolipoma in the Great West Region of France Preventing Epilepsy Using Vigabatrin In Infants With Tuberous Sclerosis Complex Early Behavioral Intervention to Improve Social Communication Function in Infants With Tuberous Sclerosis Complex Characterization of Patients With Tuberous Sclerosis Complex, Lymphangioleiomyomatosis and Angiomyolipoma Everolimus (RAD001) Therapy for Epilepsy in Patients With Tuberous Sclerosis Complex (TSC) Everolimus (RAD001) Therapy of Giant Cell Astrocytoma in Patients With Tuberous Sclerosis Complex JASPER Early Intervention for Tuberous Sclerosis Studies in Patients With Tuberous Sclerosis Complex Treatment of Renal Angiomyolipomas in Tuberous Sclerosis by Beta-blockers Efficacy and Safety of RAD001 in Patients Aged 18 and Over With Angiomyolipoma Associated With Either Tuberous Sclerosis Complex (TSC) or Sporadic Lymphangioleiomyomatosis (LAM) Efficacy and Safety of Everolimus (RAD001) in Patients of All Ages With Subependymal Giant Cell Astrocytoma Associated With Tuberous Sclerosis Complex (TSC)(EXIST-1) Long Term Follow Up for RAD001 Therapy of Angiomyolipomata in Patients With Tuberous Sclerosis (TSC) and Sporadic Lymphangioleiomyomatosis (LAM) Dose-Ranging Efficacy and Safety Study of Topical Rapamycin Cream for Facial Angiofibroma Associated With Tuberous Sclerosis Complex Dermatologic Patterns of Tuberous Sclerosis Patients and Somatic Mutation Relationship Genetic Heterogeneity and Genotype-phenotype Correlation of Children and Adults With Tuberous Sclerosis Complex (TuScCom) Early Biomarkers of Autism in Infants With Tuberous Sclerosis Complex (TSC) Tuberous Sclerosis Complex Natural History Study: Renal Manifestations Rapamycin Therapy for Patients With Tuberous Sclerosis Complex and Sporadic LAM A Study of Everolimus in the Treatment of Neurocognitive Problems in Tuberous Sclerosis Trial of RAD001 and Neurocognition in Tuberous Sclerosis Complex (TSC) Study of Skin Tumors in Tuberous Sclerosis

Brief Title

Studies in Patients With Tuberous Sclerosis Complex

Official Title

Studies in Patients With Rett Syndrome, Tuberous Sclerosis Complex, Neurofibromatoses, and Other Neurodevelopmental Disorders

Brief Summary

      This study is aimed to carry out a systematic study to examine the effects of genetic
      variants (genetic modifiers) other than TSC genes on phenotypic variability in familial TSC
      patients (affected parent, child and unaffected siblings) and sporadic TSC.
    

Detailed Description

      Tuberous sclerosis complex (TSC) is an autosomal dominant neurogenetic disorder, caused by
      heterozygous mutations in at least two different genes, TSC1, and TSC2. It is estimated to
      affect 1 in 6000, and demonstrates both phenotypic and genetic heterogeneity. It is
      characterized by a variety of symptoms including skin lesions, renal angiomyolipomas, cardiac
      rhabdomyomas, seizures, and cognitive delay (mental retardation, autism, and behavior
      problems). The severity of the disease varies widely among patients with TSC in general, and
      variability in phenotype is detectable within single families, where all affected individuals
      have the same TSC1 or TSC2 mutation. Neurocognitive phenotypes in TSC vary from profound
      mental retardation, intractable epilepsy, and autism, to normal cognition and only a mild
      behavioral phenotype. However, the basis of this phenotypic variability is not understood.
      There is a growing body of literature implicating genetic variation in "modifier genes" as an
      agent for phenotypic heterogeneity in Mendelian disorders, such as TSC. The role of genetic
      modifiers on disease severity has not yet studied in familial TSC and sporadic TSC. This
      study is aimed to carry out a systematic study to examine the effects of genetic variants
      other than TSC genes on phenotypic variability in familial TSC patients (affected parent,
      child and unaffected siblings) and sporadic TSC. The main objectives of the study are:

        1. To identify new gene mutations (genetic modifiers) in TSC familial pairs and sporadic
           cases that account for the phenotypic variability.

        2. Determination of quantitative differences in gene expression and allelic expression
           imbalance between mild and severe disease phenotype.

        3. Establish a specimen repository of familial and sporadic TSC cohort to validate the
           genetic modifiers.

      To identify genetic variants that differentiate disease severity using next generation
      sequencing (NGS) in DNA, and gene expression profile in RNA from blood to identify
      disease-causing heterozygous TSC(1 or 2) mutation in parent-child (P-C) pairs and sporadic
      cases with a mild and severe form of the disease. Use of next-generation sequencing (NGS)
      along with improved data analysis in this proposal will overcome many of the barriers in
      identifying genetic modifiers. The investigators will also study cultured fibroblasts cells
      and buccal swabs from P-C pairs to validate the findings. Use of next-generation sequencing
      (NGS) along with improved data analysis in this proposal will overcome many of the barriers
      in identifying genetic modifiers. This research has the potential to address a critical
      scientific gap in understanding the phenotypic variability The investigators may be able to
      develop a "molecular profile" that correlates with and predicts disease severity. The
      findings may provide a tool for early prediction of disease severity, allowing for the use of
      disease modifying treatments that may prevent the development of a severe neurocognitive
      phenotype.

      As this is not a treatment protocol, there is no primary endpoint.
    


Study Type

Observational


Primary Outcome

Next Generation Sequencing to Measure Phenotypic Variability


Condition

Tuberous Sclerosis Complex


Study Arms / Comparison Groups

 Familial TSC and families
Description:  Individuals with familial TSC including those with a clinical diagnosis but no genetic confirmation and individuals with a genetic diagnosis

Publications

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

Recruitment Information



Estimated Enrollment

1000

Start Date

May 2016

Completion Date

December 2021

Primary Completion Date

December 2021

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of familial TSC or sporadic TSC, or a biological relative of a person
             diagnosed with such a disorder.

          -  Willingness and ability to donate biospecimens to TGen for the purpose of propelling
             research. The minimum biospecimen donation capability is saliva and/or cheek swab. In
             most cases, blood or other tissue (skin biopsy) may be the ideal sample for study.

        Exclusion Criteria:

          -  Individuals that are 18 years or older that lack the capacity to consent for
             themselves.
      

Gender

All

Ages

N/A - N/A

Accepts Healthy Volunteers

No

Contacts

Vinodh Narayanan, 602-687-8193, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT03276195

Organization ID

vnarayanan15-016


Responsible Party

Sponsor

Study Sponsor

Translational Genomics Research Institute

Collaborators

 United States Department of Defense

Study Sponsor

Vinodh Narayanan, Principal Investigator, Translational Genomics Research Institiute (TGen)


Verification Date

April 2021