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

Tuberous Sclerosis Clinical Trial

— TESSTAL  

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

Clinical Trial Details — Status: Unknown status

Administrative data

• NCT number: NCT00490789
• Other study ID #: TESSTAL
• Status: Unknown status
• Phase: Phase 2
• First received: June 21, 2007
• Last updated: April 29, 2008
• Start date: October 2005
• Est. completion date: September 2009

Study information

• Verified date: April 2008
• Source: Cardiff University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Unknown status
• Enrollment: 14
• Est. completion date: September 2009
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Lymphangioleiomyomatosis
• Sclerosis
• Tuberous Sclerosis

Intervention

Drug:
• sirolimus
daily oral sirolimus with dosage individualised by trough blood levels

Locations

Country	Name	City	State
United Kingdom	Royal Sussex County Hospital	Brighton
United Kingdom	University Hospital of Wales	Cardiff	Wales
United Kingdom	City Hospital	Nottingham

Sponsors (6)

Lead Sponsor	Collaborator
Cardiff University	Royal Sussex County Hospital, St Georges Hospital Medical School, The Tuberous Sclerosis Association, University of Nottingham, Wyeth is now a wholly owned subsidiary of Pfizer

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	longest diameter of renal angiomyolipomas assessed by MRI scan, toxicity graded by National Cancer Institute's Common Terminology Criteria for Adverse Events v3.0		assessments at baseline and 2,6,12 and 24 months
Primary	toxicity graded by National Cancer Institute's Common Terminology Criteria for Adverse Events		throughout study
Secondary	respiratory function tests (FEV1, FVC, DLCO), cognitive function (memory, executive skills)		2 years