Tuberous SclerosisPhase 2TRONNCT01954693
A Study of Everolimus in the Treatment of Neurocognitive Problems in Tuberous Sclerosis
A Phase 2 study testing Everolimus (RAD001) in people with Tuberous Sclerosis, run by Cardiff University at 1 site in United Kingdom.
Trial summary
This is a single centre, two-arm, individually randomised, Phase II, double- blind, placebo-controlled trial of RAD001 (Everolimus) versus placebo in the treatment of neurocognitive problems in patients with tuberous sclerosis (TSC). Read more about this study
- Who is it for?
- Ages 16 to 60 years
- Conditions the study is for
- Tuberous Sclerosis
- What is being tested?
- Everolimus (RAD001)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jun 2012to 6 Aug 2018
- 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 16 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Definite TSC by current clinical criteria (28);
- Male or female aged 16 to 60 yrs;
- IQ over 60 by Wechsler Abbreviated Scales of Intelligence (WASI) and able to participate in direct neuropsychological tests;
- A score falling on, or below, the 5th percentile (approximately equivalent to -1.5 SD) in one or more of the primary outcome measures:
- Calculated GFR > 60ml/min/1.73m2 except in case of renal impairment associated with TSC complicating kidneys, where a calculated GFR should be ≥30ml/min/1.73m2;
- INR 1.5 or less (anticoagulation permitted if target INR on stable dose of warfarin or LMW heparin for > 2 weeks at time of randomisation) ;
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- Adequate liver function as shown by: serum bilirubin less than or equal to 1.5 x ULN, ALT and AST less than or equal to 2.5 x ULN;
- If sexually active - negative pregnancy test in females at the time of informed consent, contraception for males and pre-menopausal females on study);
- Seizure free or stable seizures as defined by no change in type of AEDs in 6 months prior to full recruitment and randomization at baseline. Doses of drugs may have been changed in the 6 months prior to recruitment;
- Hepatitis B surface antigen negative, Hepatitis C antibody negative.
- All patients must be able to communicate well with the investigator, to understand and comply with the requirements of the study, understand and sign the written informed consent;
- Female patients of childbearing potential must be prepared to use two acceptable methods of contraception, (e.g., intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc.), from the time of screening.
Who cannot join
- Prior treatment with an mTOR inhibitor;
- Investigational agent <30 days prior to randomisation;
- Surgery in last 2 months;
- Previous brain neurosurgery;
- Significant haematological abnormality i.e. haemoglobin < 8g/dL, platelets <80,000/mm3, absolute neutrophil count < 1000/mm3);
- Urine protein/creatinine >0.02g/mmol except in case of renal impairment associated with TSC complication of kidneys, where urine protein/creatinine ratio should be >0.1g/mmol for exclusion;
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- Serum creatinine > 1.5 x ULN except in case of renal impairment associated with TSC complication of kidneys, where serum creatinine should be >300µmol/L for exclusion;
- Uncontrolled hyperlipidaemia (fasting cholesterol > 300mg/dL or >7.75 mmol/L and fasting triglycerides >2.5 x ULN, or diabetes with fasting serum glucose > 1.5 x ULN;
- History of myocardial infarction, angina or stroke related to atherosclerosis, or any other significant cardiac disease, HIV seropositivity, organ transplant, malignancy other than squamous or basal cell skin cancer;
- lymphangioleiomyomatosis with FEV1 <70% of predicted, or any other restrictive pulmonary disease;
- Bleeding diathesis or on oral anti-vitamin K medication other than low dose warfarin;
- Pregnancy/lactation;
- Live vaccine required during trial;
- Use of strong inhibitor of CYP3AE;
- Use of strong inducer of CYP3AE except for anti epileptic drugs;
- Intercurrent infection at time of randomisation;
- Inability to complete study materials (outcome measures) in English;
- History of significant trauma-related cognitive deficit;
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of Everolimus (e.g. pancreatic insufficiency);
- Known sensitivity to Everolimus or other Rapamycin analogues or to its excipients;
- Inability to attend scheduled visits.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: TRON: A Randomised, Double Blind, Placebo-controlled Study of RAD001 (Everolimus) in the Treatment of Neurocognitive Problems in Tuberous Sclerosis
This is a single centre, two-arm, individually randomised, Phase II, double- blind, placebo-controlled trial of RAD001 (Everolimus) versus placebo in the treatment of neurocognitive problems in patients with tuberous sclerosis (TSC). The IMP is a licensed medicine in this patient group but for a different target of effect. The current trial is a proof of principle study for memory and executive function outcomes.
Following an eligibility visit, patients will be scheduled for baseline visit and randomization. They will then be followed up for 6 months undergoing both safety and neurocognitive assessments whilst taking either the placebo or study drug.
48 patients aged 16 to 60 years with tuberous sclerosis (TSC) who have IQ > 60 and a significant deficit in one or more primary outcome measures will be randomly allocated in a ratio of 2:1 to either RAD001 (Everolimus) or Placebo.
- Conditions
- Tuberous Sclerosis
- Being tested
- Placebo, Everolimus (RAD001)
- Keywords
- Tuberous Sclerosis, Everolimus, Neurocognitive functioning
- Medical subject headings
- Tuberous Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
5mg daily administered for 6 months as two oral 2.5 mg tablets once daily.
Everolimus (RAD001)Drug
5mg daily administered for 6 months as two oral 2.5 mg tablets once daily
| Study group | Role | What they receive |
|---|---|---|
| Everolimus (RAD001) | Experimental | 2x2.5mg daily Receives: Drug: Everolimus (RAD001) |
| Placebo | Placebo comparator | 2x2.5mg daily Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
List Learning test (from the BIRT Memory and Information Processing Battery)
Measured: 6 months
Complex Figure test (from the BIRT Memory and Information Processing Battery)
Measured: 6 months
CANTAB - Stockings of Cambridge (SOC)
Measured: 6 months
CANTAB - Spatial Working Memory (SWM)
Measured: 6 months
Telephone search dual task (from the Test of Everyday Attention)
Measured: 6 months
Secondary outcomes (12)
CANTAB - Rapid Visual Information Processing Battery (RVIP)
Measured: 6 months
CANTAB - Spatial Span (SSP)
Measured: 6 months
CANTAB - Attentional Set-shifting (IDED)
Measured: 6 month
Verbal Fluency /Controlled Oral Word Association Test (COWAT)
Measured: 6 months
Cancellation task
Measured: 6 months
Symptom Checklist 90R (SCL-90R)
Measured: 6 months
Quality of Life in Epilepsy (QOLIE)
Measured: 6 months
Liverpool Seizure Severity Scale (LSSS)
Measured: 6 months
Vineland Adaptive Behavior Scales-II (VABS-II) (survey form)
Measured: 6 months
Social Responsiveness Scale - Adult version (SRS-A)
Measured: 6 months
Social communication questionnaire (SCQ)
Measured: 6 months
National Adult Reading Test (NART)
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2013 (estimated)
- Study startJun 2012
- Primary completion6 Aug 2018 (estimated)
- Study completion6 Aug 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cardiff University
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Principal investigator, Julian Sampson, Cardiff University
- Investigators
- Julian Sampson, Prof, Principal investigator, Cardiff University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01954693
- Sponsor's protocol ID
- SPON803-10
- Other IDs
- 2011-004854-25
- Acronym
- TRON
- Status last verified
- Jan 2018
- First submitted
- 5 Sep 2013
- Last updated
- 30 Jan 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TRON: A Randomised, Double Blind, Placebo-controlled Study of RAD001 (Everolimus) in the Treatment of Neurocognitive Problems in Tuberous Sclerosis
- ClinicalTrials.gov ID
- NCT01954693
- Acronym / sponsor ID
- TRON / SPON803-10
- Conditions
- Tuberous Sclerosis
- Keywords
- Tuberous Sclerosis, Everolimus, Neurocognitive functioning
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Cardiff UniversityUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Jun 2012
- Primary completion
- 6 Aug 2018 (estimated)
- Study completion
- 6 Aug 2018 (estimated)
- First posted
- 7 Oct 2013 (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.
This is a single centre, two-arm, individually randomised, Phase II, double- blind, placebo-controlled trial of RAD001 (Everolimus) versus placebo in the treatment of neurocognitive problems in patients with tuberous sclerosis (TSC). The IMP is a licensed medicine in this patient group but for a different target of effect. The current trial is a proof of principle study for memory and executive function outcomes.
Following an eligibility visit, patients will be scheduled for baseline visit and randomization. They will then be followed up for 6 months undergoing both safety and neurocognitive assessments whilst taking either the placebo or study drug.
48 patients aged 16 to 60 years with tuberous sclerosis (TSC) who have IQ > 60 and a significant deficit in one or more primary outcome measures will be randomly allocated in a ratio of 2:1 to either RAD001 (Everolimus) or Placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Everolimus (RAD001) | Experimental | Drug: Everolimus (RAD001)2x2.5mg daily |
| Placebo | Placebo comparator | Drug: Placebo2x2.5mg daily |
Who may qualify
- Ages
- 16 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (12 listed)
- Definite TSC by current clinical criteria (28);
- Male or female aged 16 to 60 yrs;
- IQ over 60 by Wechsler Abbreviated Scales of Intelligence (WASI) and able to participate in direct neuropsychological tests;
- A score falling on, or below, the 5th percentile (approximately equivalent to -1.5 SD) in one or more of the primary outcome measures:
- Calculated GFR > 60ml/min/1.73m2 except in case of renal impairment associated with TSC complicating kidneys, where a calculated GFR should be ≥30ml/min/1.73m2;
Key exclusion criteria (21 listed)
- Prior treatment with an mTOR inhibitor;
- Investigational agent <30 days prior to randomisation;
- Surgery in last 2 months;
- Previous brain neurosurgery;
- Significant haematological abnormality i.e. haemoglobin < 8g/dL, platelets <80,000/mm3, absolute neutrophil count < 1000/mm3);
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 |
|---|---|---|
| Placebo5mg daily administered for 6 months as two oral 2.5 mg tablets once daily. | Drug | Placebo |
| Everolimus (RAD001)5mg daily administered for 6 months as two oral 2.5 mg tablets once daily | Drug | Everolimus (RAD001) |
Primary outcome
List Learning test (from the BIRT Memory and Information Processing Battery)
Time frame: 6 months
Complex Figure test (from the BIRT Memory and Information Processing Battery)
Time frame: 6 months
CANTAB - Stockings of Cambridge (SOC)
Time frame: 6 months
CANTAB - Spatial Working Memory (SWM)
Time frame: 6 months
Telephone search dual task (from the Test of Everyday Attention)
Time frame: 6 months
12 secondary outcomes
CANTAB - Rapid Visual Information Processing Battery (RVIP)
Time frame: 6 months
CANTAB - Spatial Span (SSP)
Time frame: 6 months
CANTAB - Attentional Set-shifting (IDED)
Time frame: 6 month
Verbal Fluency /Controlled Oral Word Association Test (COWAT)
Time frame: 6 months
Cancellation task
Time frame: 6 months
Symptom Checklist 90R (SCL-90R)
Time frame: 6 months
Quality of Life in Epilepsy (QOLIE)
Time frame: 6 months
Liverpool Seizure Severity Scale (LSSS)
Time frame: 6 months
Vineland Adaptive Behavior Scales-II (VABS-II) (survey form)
Time frame: 6 months
Social Responsiveness Scale - Adult version (SRS-A)
Time frame: 6 months
Social communication questionnaire (SCQ)
Time frame: 6 months
National Adult Reading Test (NART)
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2018.
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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 Sampson, Prof principal investigator
Cardiff University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Everolimus (RAD001) in people with Tuberous Sclerosis, run by Cardiff University at 1 site 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 12 inclusion and 21 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 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. Some participants in this study may receive a placebo. 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?
List Learning test (from the BIRT Memory and Information Processing Battery) (time frame: 6 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Jan 2018; AzTrials last refreshed its copy on 8 Nov 2026.