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

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

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