Trial of Efficacy and Safety of Sirolimus in Tuberous Sclerosis and LAM (TESSTAL)
The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2008 by Cardiff University.
Recruitment status was Active, not recruiting
Recruitment status was Active, not recruiting
Sponsor:
Cardiff University
Collaborators:
University of Nottingham
St Georges Hospital Medical School
Royal Sussex County Hospital
The Tuberous Sclerosis Association
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by:
Cardiff University
ClinicalTrials.gov Identifier:
NCT00490789
First received: June 21, 2007
Last updated: April 29, 2008
Last verified: April 2008
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Tuberous Sclerosis Lymphangioleiomyomatosis |
Drug: sirolimus |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
Resource links provided by NLM:
Further study details as provided by Cardiff University:
Primary Outcome Measures:
- 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 Measures:
- respiratory function tests (FEV1, FVC, DLCO), cognitive function (memory, executive skills) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 14 |
| Study Start Date: | October 2005 |
| Estimated Study Completion Date: | September 2009 |
| Estimated Primary Completion Date: | September 2009 (Final data collection date for primary outcome measure) |
Intervention Details:
Detailed Description:
-
Drug: sirolimus
- rapamune
- rapamycin
daily oral sirolimus with dosage individualised by trough blood levels
Other Names:
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
Eligibility| Ages Eligible for Study: | 18 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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)
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00490789
Locations
| United Kingdom | |
| University Hospital of Wales | |
| Cardiff, Wales, United Kingdom, CF14 4XN | |
| Royal Sussex County Hospital | |
| Brighton, United Kingdom, BN2 5BE | |
| City Hospital | |
| Nottingham, United Kingdom, NG5 1PB | |
Sponsors and Collaborators
Cardiff University
University of Nottingham
St Georges Hospital Medical School
Royal Sussex County Hospital
The Tuberous Sclerosis Association
Wyeth is now a wholly owned subsidiary of Pfizer
Investigators
| Principal Investigator: | Julian R Sampson, DM | Cardiff Univeristy |
More Information
No publications provided by Cardiff University
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Julian R Sampson, Cardiff University |
| ClinicalTrials.gov Identifier: | NCT00490789 History of Changes |
| Other Study ID Numbers: | TESSTAL |
| Study First Received: | June 21, 2007 |
| Last Updated: | April 29, 2008 |
| Health Authority: | United Kingdom: Research Ethics Committee United Kingdom: Medicines and Healthcare Products Regulatory Agency |
Keywords provided by Cardiff University:
|
tuberous sclerosis lymphangioleiomyomatosis sirolimus |
angiomyolioma rapamycin mTOR |
Additional relevant MeSH terms:
|
Sclerosis Tuberous Sclerosis Lymphangioleiomyomatosis Pathologic Processes Hamartoma Neoplasms Malformations of Cortical Development Nervous System Malformations Nervous System Diseases Neurocutaneous Syndromes Heredodegenerative Disorders, Nervous System Neurodegenerative Diseases Congenital Abnormalities Genetic Diseases, Inborn Lymphangiomyoma |
Lymphatic Vessel Tumors Neoplasms by Histologic Type Perivascular Epithelioid Cell Neoplasms Neoplasms, Connective and Soft Tissue Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Sirolimus Everolimus Antibiotics, Antineoplastic Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Antifungal Agents |
ClinicalTrials.gov processed this record on May 19, 2013