View clinical trials related to Tuberous Sclerosis.
Filter by:Tuberous Sclerosis Complex (TSC) is a multisystemic autosomal dominant disease that is characterized by the development of benign neoplasms in brain, kidney, lung, skin and heart. TSC is caused by mutations in TSC1 and/or TSC2 genes, which encode, respectively, hamartin and tuberin, that are involved in the regulation of cell proliferation, cell cycle and protein synthesis. Most patients exhibit dermatological, renal, neurological and pulmonary (lymphangioleiomyomatosis, LAM) manifestations. Neurological involvement include subependymal nodules, subependymal giant cell astrocytomas and cortical tubers. LAM is characterized by the proliferation of LAM cells around the airways, blood vessels and lymphatics, which result in vascular and airway obstruction and cyst formation. The most frequent TSC manifestation in the kidney is the development of angiomyolipomas (AML). Dermatologic lesions represent the most common manifestations of TSC, mainly hypomelanotic macules and facial angiofibromas. The most significant functional implication of the tuberin-hamartin complex is its regulatory role upon the mammalian target of rapamycin (mTOR) pathway. Mutations in TSC1 or TSC2 lead to increased mTOR activity and favor tumor development and growth. All lesions associated with TSC, sporadic LAM and sporadic AML share a common molecular pathogenesis, based on TSC1/TSC2 mutations and mTOR hyperactivity. Up to date, TSC patients have been followed in separated medical services in our institution, according to their predominant phenotype. The current knowledge, however, suggest that the ideal follow up of such patients should be conducted in an integrated fashion among the specialties associated with the main disease manifestations. Experts in TSC from each of these areas have recently created a TSC/LAM/AML integrated program in the University of São Paulo Medical Center, and his project will be initiated with the generation of an integrated TSC/LAM/AML registry, which intends not only to clinically characterize this patient population but also to document the employed treatment modalities. Once this first goal is achieved, clinical trials are planned to be performed. The central aim of this observational study is to clinically characterize the TSC/LAM/AML subject population followed and referred to the University of São Paulo Medical Center. Specific aims: To characterize the pulmonary, the neurological, the renal and the dermatologic phenotypes of this patient population.
In this research study, the investigators are evaluating the clinical benefit of everolimus in cancer patients with inactivating TSC1 or TSC2 mutations or activating MTOR mutations. This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug called everolimus to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug is being studied. It also means that the FDA (the U.S. Food and Drug Administration) has not yet approved everolimus for your type of cancer. Everolimus is a drug that may stop cancer cells from growing by blocking an important factor (mTOR) involved in the growth of cells. This drug has been used in treatment for other cancers and is approved by the Food and Drug Administration for treatment of several types of cancer, including renal cell carcinoma. Treatment with this drug has been associated with responses in some patients whose cancers had mutations in TSC1 or TSC2. The investigators think that patients whose tumors have mutations in TSC1 or TSC2 may have a good chance of responding to treatment with drugs like everolimus.
Treatment of angiomyolipomas is based on invasive techniques such as surgery or embolization. Development of anti-angiogenic therapies is a major and growing field of research in hypervascularized tumors. Angiomyolipomas have been shown to regress after prolonged treatment with mTOR inhibitors (Sirolimus), but with a large proportion of secondary effects. We showed recently that beta-blockers were able to induce regression of infantile hemagiomas. Consequently, we looked for and found, histologically, in a few cases of angiomyolipomas the presence of beta2 receptors. The aim of the study is to estimate if beta-blockers could induce regression or stabilization of renal angiomyolipomas in tuberous sclerosis in a pilot study.
The primary objective of clinical part of EPISTOP project is to identify the clinical and molecular biomarkers of epileptogenesis in a prospective clinical study of patients with TSC. Secondary objective of the clinical part of EPISTOP is to compare the effects of standard antiepileptic treatment in patients diagnosed as having epilepsy after clinical seizures vs after electroencephalographic epileptiform discharges, in a randomized trial in TSC patients.
The purpose of this research study is to see if simvastatin can be taken safely in patients with either LAM or TSC, who are already being treated with everolimus or sirolimus. This is the first step in looking at simvastatin as a drug that may help patients, by impacting the growth and survival of cells that make up the lung lesions that cause problems in LAM and TSC patients. The study also seeks to learn more about how simvastatin works, when given to patients being treated with everolimus or sirolimus, and to evaluate the safety and any potential benefit to patients taking this 2-drug combination. The primary objective of this study is to determine the safety of simvastatin in the treatment of LAM-S or LAM-TS in patients on a stable (for at least 3 months) dose of sirolimus or everolimus. Secondary objectives include: - To assess the effect of simvastatin on forced expiratory volume in 1 second (FEV1). - To assess the effect of simvastatin on forced vital capacity (FVC). - To assess the effect of simvastatin on diffusing lung capacity (DLCO). - To assess the effect of simvastatin on vascular endothelial growth factor -D (VEGF-D) serum levels. - To assess the effect of simvastatin with questionnaire- based assessments of dyspnea, fatigue, and quality of life (QOL). - Assess signs of clinical benefit.
This is a single centre, two-arm, individually randomised, Phase II, double- blind, placebo-controlled trial of RAD001 (Everolimus) versus placebo in the treatment of neurocognitive problems in patients with tuberous sclerosis (TSC). The IMP is a licensed medicine in this patient group but for a different target of effect. The current trial is a proof of principle study for memory and executive function outcomes. Following an eligibility visit, patients will be scheduled for baseline visit and randomization. They will then be followed up for 6 months undergoing both safety and neurocognitive assessments whilst taking either the placebo or study drug. 48 patients aged 16 to 60 years with tuberous sclerosis (TSC) who have IQ > 60 and a significant deficit in one or more primary outcome measures will be randomly allocated in a ratio of 2:1 to either RAD001 (Everolimus) or Placebo.
The purpose of this study is to assess the feasibility and safety of administering rapalogues, sirolimus or everolimus, in participants with Tuberous Sclerosis Complex (TSC) and self-injury and to measure cognitive and behavioral changes, including reduction in autistic symptoms, self-injurious and aggressive behaviors, as well as improvements in cognition across multiple domains of cognitive function.
The objective of this study is to evaluate the safety and efficacy of a 0.1% formulation of rapamune cream in children with Tuberous Sclerosis Complex (TSC), ages 3 years and older, who have facial angiofibromas that would benefit from treatment.
The investigators are enrolling 3-12 month old infants with a diagnosis of tuberous sclerosis complex (TSC) for a new study on early markers of autism. The study is looking for early signs for autism in a population (TSC) where autism is common. The goal of this project is to use behavioral testing, MRI and EEG techniques to identify children at risk for developing autism starting at 3 months of age and continuing until 36 months of age. Throughout the study, the investigators will recommend Early Intervention services for any child who shows early signs of autism.
To determine whether EEGs during infancy is a reliable biomarker to identify TSC patients that will develop infantile spasms/epilepsy in the near future and thus are appropriate candidates for an antiepileptogenic drug trial. Since not all patients with TSC develop epilepsy, it would be useful to have a biomarker that could predict those patients destined to have epilepsy and thus identify those TSC patients most appropriate for an antiepileptogenic drug trial. A recent study suggests that treating TSC patients with an abnormal EEG prior to onset of infantile spasms with vigabatrin may improve neurological outcome, but the use of EEG as a reliable biomarker of future epilepsy has not been rigorously validated. In this specific aim, we will test the reliability of EEG in predicting future development of infantile spasms or epilepsy in TSC patients during the first year of life.