Brief Title
Trial of Efficacy and Safety of Sirolimus in Tuberous Sclerosis and LAM
Official Title
A Trial of the Efficacy and Safety of Sirolimus(Rapamycin)Therapy for Renal Angiomyolipmoas in Patients With Tuberous Sclerosis Complex and Sporadic Lymphangioleiomyomatosis
Brief Summary
The purpose of this study is to determine the safety and efficacy of the mTOR inhibitor
sirolimus as a treatment for renal angiomyolipomas in patients with tyberous sclerosis
complex or sporadic lymphangioleiomyomatosis.
Detailed Description
Inherited mutations of the TSC1 or TSC2 gene cause tuberous sclerosis while acquired
(somatic) mutations of either gene are associated with sporadic lymphangioleiomyomatosis
(LAM). Renal angiomyolipomas are a feature of both disorders. TSC1 and TSC2 regulate
signalling through the mammalian target of rapamycin (mTOR) pathway. Inhibition of mTOR may
result in a decrease in size of TSC 1/2 assciated lesions. We are treating patients with
tuberous sclerosis or sporadic LAM with the mTOR inhibitor rapamycin in a non-randomised,
open label pilot study of safety and efficacy. Change in size of renal angiomyolipomas is the
primary end point
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
longest diameter of renal angiomyolipomas assessed by MRI scan, toxicity graded by National Cancer Institute's Common Terminology Criteria for Adverse Events v3.0
Secondary Outcome
respiratory function tests (FEV1, FVC, DLCO), cognitive function (memory, executive skills)
Condition
Tuberous Sclerosis
Intervention
sirolimus
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
14
Start Date
October 2005
Completion Date
September 2009
Primary Completion Date
September 2009
Eligibility Criteria
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)
Gender
All
Ages
18 Years - 65 Years
Accepts Healthy Volunteers
No
Contacts
Julian R Sampson, DM, ,
Location Countries
United Kingdom
Location Countries
United Kingdom
Administrative Informations
NCT ID
NCT00490789
Organization ID
TESSTAL
Study Sponsor
Cardiff University
Collaborators
University of Nottingham
Study Sponsor
Julian R Sampson, DM, Principal Investigator, Cardiff Univeristy
Verification Date
April 2008