Clinical Trial: Characterization of Patients With Tuberous Sclerosis Complex, Lymphangioleiomyomatosis and Angiomyolipoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational [Patient Registry]

Official Title: Clinical Profile Characterization of Patients With Tuberous Sclerosis Complex, Lymphangioleiomyomatosis and Angiomyolipoma Followed at Hospital Das Clínicas, Universi

Brief Summary: 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 no

Detailed Summary:

  1. Introduction Tuberous Sclerosis Complex (TSC) is a multisystemic autosomal dominant disease , that is characterized by the development of histologically benign neoplasms in brain, kidney, lung, skin, heart and eyes, as well as by central nervous system (CNS) disorganization. TSC is caused by mutations in TSC1 (Tuberous Sclerosis Complex 1) and/or TSC2 genes, which encode, respectively, hamartin and tuberin, proteins that form a complex involved in the regulation of cell proliferation, cell cycle and protein synthesis. Although the majority of organs are susceptible, most patients exhibit dermatological, renal, neurological and pulmonary manifestations.

    Involvement of the CNS responds for most of TSC morbidity and include subependymal nodules, subependymal giant cell astrocytomas (SEGA) and cortical tubers, alterations prone to lead to ventricular obstruction, hydrocephalus, epilepsy, intellectual disability and psychiatric problems.

    Lymphangioleiomyomatosis (LAM) is a rare disease that is characterized by the proliferation of LAM cells around the airways, blood vessels and lymphatics, which can result in vascular and airway obstruction and cyst formation. LAM occurs sporadically or in association with tuberous sclerosis complex. The main clinical features are dyspnea, pneumothorax and chylothorax.

    The most frequent TSC manifestation in the kidney is the development of angiomyolipomas (AML), a tumor derived from perivascular epithelioid cells that comprises abnormally organized blood vessels, smooth muscle cells and adipose tissue. AML affects 60-80% of TSC patients, but it also occurs sporadically. The main AML-related complication is renal hemorrhage, the most common cause of mortality in adults
    Sponsor: InCor Heart Institute

    Current Primary Outcome:

    • Pulmonary function tests [ Time Frame: Baseline and change after one year ]
    • Chest high resolution computed tomography findings [ Time Frame: Baseline and change after one year ]
    • Findings on computed tomography of the brain [ Time Frame: Baseline and change after one year ]
    • Abdominal computed tomography findings [ Time Frame: Baseline and change after one year ]
    • Skin lesions [ Time Frame: Baseline and change after one year ]
      Describe skin lesions in the study population
    • Respiratory symptoms Describe all respiratory symptoms in the study population) [ Time Frame: Baseline and change after one year ]
      Describe all respiratory symptoms in the study population
    • Quality of life evaluation with the questionnaire Short-Form Health Survey - 36 (SF-36) [ Time Frame: Baseline and change after one year ]
    • Urinary and abdominal complaints [ Time Frame: Baseline and change after one year ]
      Describe urinary and abdominal complaints in the study population
    • Baseline dyspna index [ Time Frame: Baseline and change after one year ]
      Assessment of the degree of dyspnea using baseline dyspnea index
    • Treatments performed (previous and current treatments performed) [ Time Frame: Baseline ]
      Same as current

      Current Secondary Outcome:

      • Six-minute walking distance and dessaturation during six-minute walk test [ Time Frame: Baseline and change after one year ]
      • Systolic pulmonary arterial pressure [ Time Frame: Baseline and after one year ]
        This valuable will be evaluated by transthoracic echocardiography
      • Changes in electroencephalogram [ Time Frame: Baseline and after one year ]
      • Loss of productivity and hospitalizations [ Time Frame: Baseline and after one year ]
      • Histopathological characteristics of samples obtained from skin biopsy [ Time Frame: Baseline ]
        If there is a skin lesion, it might be biopsied and evaluated by a pathologist


      Original Secondary Outcome: Same as current

      Information By: InCor Heart Institute

      Dates:
      Date Received: December 14, 2014
      Date Started: April 2016
      Date Completion: April 2018
      Last Updated: August 29, 2016
      Last Verified: August 2016