Trial of Efficacy and Safety of Sirolimus in Tuberous Sclerosis and LAM

Inclusion Criteria: * If female, documentation of negative pregnancy test prior to enrolment. * Participants, including males, must use an effective form of contraception, whilst taking sirolimus and for twelve weeks after stopping the drug * One or more renal angiomyolipomata of at least two centimetres or greater in largest diameter * Adequate renal function :glomerular filtration rate \> 40 ml/min * Clinically definite diagnosis of tuberous sclerosis (modified Gomez criteria) or sporadic LAM (biopsy-proven or compatible high resolution chest CT scan and respiratory function tests.) * Signed and dated informed consent Exclusion Criteria: * History of non-compliance or inability to give informed consent * Significant haematological or hepatic abnormality (i.e. transaminase levels \> 150 i.u./L serum albumin \< 30 g/L, haematocrit\< 30%, platelets \< 100,000/ mm3, adjusted absolute neutrophil count \< 1,500/mm3, total WBC \< 3,000/ mm3) * Greater than 1 g proteinuria daily * Multiple bilateral AMLs, where individual lesions cannot be distinguished * Renal haemorrhage within preceding year * In those who have had a renal haemorrhage, known conservatively managed renal aneurysm(s) greater than 10mm * Patients who have had embolisation for AML(s) within the preceding 6 months * Patients who are unable to walk 100 metres on the flat * Continuous requirement for supplemental oxygen * Patients who have had or are being considered for organ transplant * Uncontrolled hyperlipidaemia * Intercurrent infection at initiation of Sirolimus * Surgery within last 2 months * Pregnant or lactating women * Use of an investigational drug within the last 30 days * Change in anti epileptic drug medication within the last 3 months * Likely to need vaccination e.g. for travel during the course of the trial (except for influenza vaccine in patients with LAM) * Current usage of strong inhibitors of CYP3AE ( such as ketoconazole, voriconazole, itraconazole, tilithromycin or clarithromycin) or strong inducers (such as rifampicin or rifabutin)