Tuberous Sclerosis ComplexNCT03276195
Studies in Patients With Tuberous Sclerosis Complex
An observational study of Tuberous Sclerosis Complex, run by Translational Genomics Research Institute at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Tuberous Sclerosis Complex
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2016to 27 Nov 2023
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: This study will enroll subjects affected with Tuberous Sclerosis Complex (either familial or sporadic) and biological relatives (primarily the individual's parents or siblings). This study will consist of 1000 families who have an individual affected with TSC and wish to donate samples.
Who may be able to join
- 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.
Who cannot join
- Individuals that are 18 years or older that lack the capacity to consent for themselves.
Trial locations and contacts
1 site in 1 country.
United States1 site
Translational Genomics Research Institute (TGen)
Phoenix, Arizona, 85004
About this study
Official title: Studies in Patients With Rett Syndrome, Tuberous Sclerosis Complex, Neurofibromatoses, and Other Neurodevelopmental Disorders
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.
Read the 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:
- To identify new gene mutations (genetic modifiers) in TSC familial pairs and sporadic cases that account for the phenotypic variability.
- Determination of quantitative differences in gene expression and allelic expression imbalance between mild and severe disease phenotype.
- 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.
- Conditions
- Tuberous Sclerosis Complex
- Keywords
- Neurodevelopmental Disorder, Genomics, Genetics
- Medical subject headings
- Tuberous Sclerosis, Neurodevelopmental Disorders
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 |
|---|---|---|
| Familial TSC and families | Individuals with familial TSC including those with a clinical diagnosis but no genetic confirmation and individuals with a genetic diagnosis | |
| Sporadic TSC and families | Individuals with sporadic TSC including those with a clinical diagnosis but no genetic confirmation and individuals with a genetic diagnosis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Next Generation Sequencing to Measure Phenotypic Variability
Identify genetic variants and disease mechanisms responsible for phenotypic variability among patients who are diagnosed with Tuberous Sclerosis Complex (TSC) and their family members.
Measured: Up to 4 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2017
- Study start1 May 2016
- Primary completion27 Nov 2023
- Study completion27 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tuberous Sclerosis ComplexStudies 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
- Family based
- Time perspective
- Prospective
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Translational Genomics Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Sponsor
- Investigators
- Vinodh Narayanan, Principal investigator, Translational Genomics Research Institiute (TGen)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03276195
- Sponsor's protocol ID
- vnarayanan15-016
- Status last verified
- Nov 2023
- First submitted
- 28 Apr 2017
- Last updated
- 29 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: De-identified participant study data will be published to a central data repository that allows qualified research scientists to access and look at the data under controlled access.
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Studies in Patients With Rett Syndrome, Tuberous Sclerosis Complex, Neurofibromatoses, and Other Neurodevelopmental Disorders
- ClinicalTrials.gov ID
- NCT03276195
- Acronym / sponsor ID
- vnarayanan15-016
- Conditions
- Tuberous Sclerosis Complex
- Keywords
- Neurodevelopmental Disorder, Genomics, Genetics
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Translational Genomics Research InstituteUniversity, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- 1 May 2016 (actual)
- Primary completion
- 27 Nov 2023 (actual)
- Study completion
- 27 Nov 2023 (actual)
- First posted
- 8 Sep 2017 (actual)
- 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.
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:
- To identify new gene mutations (genetic modifiers) in TSC familial pairs and sporadic cases that account for the phenotypic variability.
- Determination of quantitative differences in gene expression and allelic expression imbalance between mild and severe disease phenotype.
- 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 design
- Observational model
- Family based
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Familial TSC and families | – | –Individuals with familial TSC including those with a clinical diagnosis but no genetic confirmation and individuals with a genetic diagnosis |
| Sporadic TSC and families | – | –Individuals with sporadic TSC including those with a clinical diagnosis but no genetic confirmation and individuals with a genetic diagnosis |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- This study will enroll subjects affected with Tuberous Sclerosis Complex (either familial or sporadic) and biological relatives (primarily the individual's parents or siblings). This study will consist of 1000 families who have an individual affected with TSC and wish to donate samples.
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (1 listed)
- Individuals that are 18 years or older that lack the capacity to consent for themselves.
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
Next Generation Sequencing to Measure Phenotypic Variability
Time frame: Up to 4 Years
Identify genetic variants and disease mechanisms responsible for phenotypic variability among patients who are diagnosed with Tuberous Sclerosis Complex (TSC) and their family members.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2023.
- Individual participant dataSharing planned: Yes. De-identified participant study data will be published to a central data repository that allows qualified research scientists to access and look at the data under controlled access.
Related trials for Tuberous Sclerosis Complex
RecruitingObservational study
Study of Skin Tumors in Tuberous Sclerosis
Tuberous Sclerosis
RecruitingObservational study
Role of Genetic Factors in the Development of Lung Disease
Cystic Fibrosis, Pulmonary Fibrosis
RecruitingPhase 2/3
Efficacy and Safety of Rapamycin Versus Vigabatrin in the Prevention of Tuberous Sclerosis Complex Symptoms in Infants
Tuberous Sclerosis Complex
RecruitingPhase 3
Placebo Controlled Study to Assess the Efficacy and Safety of Rapamycin in Drug Resistant Epilepsy Associated With Tuberous Sclerosis Complex
Tuberous Sclerosis Complex
RecruitingObservational study
Study of the Disease Process of Lymphangioleiomyomatosis
Lung Disease, Pneumothorax
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.
Vinodh Narayanan principal investigator
Translational Genomics Research Institiute (TGen)
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 Tuberous Sclerosis Complex, run by Translational Genomics Research Institute at 1 site in United States.
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 2 inclusion and 1 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: finished, as of the sponsor's last update on 29 Nov 2023. 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 United States. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Next Generation Sequencing to Measure Phenotypic Variability (time frame: Up to 4 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 29 Nov 2023.