Tuberous SclerosisPhase 2TESSTALNCT00490789
Trial of Efficacy and Safety of Sirolimus in Tuberous Sclerosis and LAM
A Phase 2 study testing sirolimus in people with Tuberous Sclerosis and Lymphangioleiomyomatosis, run by Cardiff University at 3 sites in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Tuberous Sclerosis, Lymphangioleiomyomatosis
- What is being tested?
- sirolimus
- Type of treatment
- Pill or oral medicine
- How many people
- 14 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- Oct 2005to Sep 2009
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 18Show fewer
- 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)
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
Royal Sussex County Hospital
Brighton, BN2 5BE
University Hospital of Wales
Cardiff, Wales, CF14 4XN
City Hospital
Nottingham, NG5 1PB
About this study
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
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.
Read the 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
- Conditions
- Tuberous Sclerosis, Lymphangioleiomyomatosis
- Being tested
- sirolimus
- Keywords
- tuberous sclerosis, lymphangioleiomyomatosis, sirolimus, angiomyolioma, rapamycin, mTOR
- Medical subject headings
- Tuberous Sclerosis, Lymphangioleiomyomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sirolimusDrug
Also called rapamune, rapamycin
daily oral sirolimus with dosage individualised by trough blood levels
What is being measured
The primary outcome is the main question the study is designed to answer.
longest diameter of renal angiomyolipomas assessed by MRI scan, toxicity graded by National Cancer Institute's Common Terminology Criteria for Adverse Events v3.0
Measured: assessments at baseline and 2,6,12 and 24 months
toxicity graded by National Cancer Institute's Common Terminology Criteria for Adverse Events
Measured: throughout study
Secondary outcomes (1)
respiratory function tests (FEV1, FVC, DLCO), cognitive function (memory, executive skills)
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2007 (estimated)
- Study startOct 2005
- Primary completionSep 2009 (estimated)
- Study completionSep 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Tuberous SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cardiff University
- Sponsor type
- University, hospital or other
- 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
- Investigators
- Julian R Sampson, DM, Principal investigator, Cardiff Univeristy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00490789
- Sponsor's protocol ID
- TESSTAL
- Acronym
- TESSTAL
- Status last verified
- Apr 2008
- First submitted
- 21 Jun 2007
- Last updated
- 30 Apr 2008
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Davies DM, de Vries PJ, Johnson SR, McCartney DL, Cox JA, Serra AL, Watson PC, Howe CJ, Doyle T, Pointon K, Cross JJ, Tattersfield AE, Kingswood JC, Sampson JR. Sirolimus therapy for angiomyolipoma in tuberous sclerosis and sporadic lymphangioleiomyomatosis: a phase 2 trial. Clin Cancer Res. 2011 Jun 15;17(12):4071-81. doi: 10.1158/1078-0432.CCR-11-0445. Epub 2011 Apr 27.
PubMed 21525172
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00490789
- Acronym / sponsor ID
- TESSTAL / TESSTAL
- Conditions
- Tuberous Sclerosis, Lymphangioleiomyomatosis
- Keywords
- tuberous sclerosis, lymphangioleiomyomatosis, sirolimus, angiomyolioma, rapamycin, mTOR
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 14 participants (estimated)
- Lead sponsor
- Cardiff UniversityUniversity, hospital or other
- 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
- Study start
- Oct 2005
- Primary completion
- Sep 2009 (estimated)
- Study completion
- Sep 2009 (estimated)
- First posted
- 25 Jun 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.)
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sirolimusAlso: rapamune, rapamycindaily oral sirolimus with dosage individualised by trough blood levels | Drug | – |
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
Time frame: assessments at baseline and 2,6,12 and 24 months
toxicity graded by National Cancer Institute's Common Terminology Criteria for Adverse Events
Time frame: throughout study
1 secondary outcome
respiratory function tests (FEV1, FVC, DLCO), cognitive function (memory, executive skills)
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2008.
- Derived from this study: PubMed 21525172Davies DM, de Vries PJ, Johnson SR, McCartney DL, Cox JA, Serra AL, Watson PC, Howe CJ, Doyle T, Pointon K, Cross JJ, Tattersfield AE, Kingswood JC, Sampson JR. Sirolimus therapy for angiomyolipoma in tuberous sclerosis and sporadic lymphangioleiomyomatosis: a phase 2 trial. Clin Cancer Res. 2011 Jun 15;17(12):4071-81. doi: 10.1158/1078-0432.CCR-11-0445. Epub 2011 Apr 27.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julian R Sampson, DM principal investigator
Cardiff Univeristy
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing sirolimus in people with Tuberous Sclerosis and Lymphangioleiomyomatosis, run by Cardiff University at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Apr 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00490789, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2008.