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Trial of Efficacy and Safety of Sirolimus in Tuberous Sclerosis and LAM (TESSTAL)

This study is ongoing, but not recruiting participants.
Information provided by Cardiff University

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Descriptive Information Fields
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 II
Study Type  Interventional
Study Design  Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Primary Outcome Measure  longest diameter of renal angiomyolipomas assessed by MRI scan, toxicity graded by National Cancer Institute's Common Terminology Criteria for Adverse Events v3.0 [ Time Frame: assessments at baseline and 2,6,12 and 24 months ] [ Designated as safety issue: No ]
toxicity graded by National Cancer Institute's Common Terminology Criteria for Adverse Events [ Time Frame: throughout study ] [ Designated as safety issue: Yes ]
Secondary Outcome Measure  respiratory function tests (FEV1, FVC, DLCO), cognitive function (memory, executive skills) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Condition  Tuberous Sclerosis
Lymphangioleiomyomatosis
Intervention  Drug: sirolimus
MEDLINE PMIDs
Links
Recruitment Information Fields
Recruitment Status  Active, not recruiting
Enrollment  14
Start Date  October 2005
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 Both
Ages 18 Years to 65 Years
Accepts Healthy Volunteers No
Contacts ††
Location Countries  United Kingdom
Administrative Information Fields
NCT ID  NCT00490789
Organization ID TESSTAL
Secondary IDs ††
Study Sponsor  Cardiff University
Collaborators †† University of Nottingham
St Georges Hospital Medical School
Royal Sussex County Hospital
Wales Gene Park
The Tuberous Sclerosis Association
Wyeth
Investigators 
Principal Investigator:     Julian R Sampson, DM     Cardiff Univeristy    
Information Provided By Cardiff University
Verification Date April 2008
First Received Date  June 21, 2007
Last Updated Date April 29, 2008

 †    Required WHO trial registration data element.
††   WHO trial registration data element that is required only if it exists.




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