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| [ ...Back to search results ] | [ Print-friendly version ] |
| A randomised, double blind, placebo-controlled study of RAD001 (Everolimus) in the treatment of neurocognitive problems in tuberous sclerosis |
| ISRCTN | ISRCTN09739757 |
| ClinicalTrials.gov identifier | |
| Public title | A randomised, double blind, placebo-controlled study of RAD001 (Everolimus) in the treatment of neurocognitive problems in tuberous sclerosis |
| Scientific title | A randomised, double blind, placebo-controlled study of RAD001 (Everolimus) in the TReatment Of Neurocognitive problems in tuberous sclerosis (TRON) |
| Acronym | TRON |
| Serial number at source | SPON803-10 |
| Study hypothesis | Are the recall memory and executive function in people with tuberous sclerosis (TSC) improved after treatment with RAD001 (Everolimus) or placebo for 6 months? |
| Lay summary | Lay summary under review |
| Ethics approval | Not provided at time of registration |
| Study design | A single centre two-arm individually randomised phase II double-blind placebo-controlled trial |
| Countries of recruitment | United Kingdom |
| Disease/condition/study domain | Tuberous sclerosis |
| Participants - inclusion criteria |
1. Definite TSC by current clinical criteria
2. Male or female aged 16 to 60 years 3. IQ over 60 by Wechsler Abbreviated Scales of Intelligence (WASI) and able to participate in direct neuropsychological tests 4. Deficit of -2S.D. or more below normal population mean on a primary outcome measure 5. Calculated glomerular filtration rate (GFR) > 60ml/min/1.73m2 6. International Normalized Ratio (INR) 1.5 or less (anticoagulation permitted if target INR on stable dose of warfarin or Low molecular weight (LMW) heparin for > 2 weeks at time of randomisation) 7. Adequate liver function as shown by: serum bilirubin less than or equal to 1.5 x upper limit of normal (ULN), alanine aminotranferease (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 x ULN 8. If sexually active - negative pregnancy test in females at the time of informed consent, contraception for males and pre-menopausal females on study 9. Seizure free or stable seizures as defined by no change in type of antiepileptic drugs (AEDs) in 6 months prior to recruitment. Doses of drugs may have been changed in the 6 months prior to recruitment 10. Negative Hepatitis B virus (HBV) DNA and Hepatitis C virus (HCV) RNA , polymerase chain reaction (PCR) testing at screening for patients with a positive history of risk factors and/or confirmation of prior HBV/HCV infection 11. 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 12. 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 |
| Participants - exclusion criteria |
1. Prior treatment with an mTOR (mammalian target of rapamycin) inhibitor
2. Investigational agent <30 days prior to randomisation 3. Surgery in last 2 months 4. Previous brain neurosurgery 5. Significant haematological abnormality i.e. haemoglobin < 8g/dL, platelets <80,000/mm3, absolute neutrophil count < 1000/mm3) 6. Urine protein/creatinine >0.02g/mmol 7. Serum creatinine > 1.5 x ULN 8. 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 9. History of myocardial infarction, angina or stroke related to atherosclerosis, or any other significant cardiac disease, human immunodeficiency virus (HIV) seropositivity, organ transplant, malignancy other than squamous or basal cell skin cancer 10. Lymphangioleiomyomatosis with forced expiratory volume in 1 second (FEV1) <70% of predicted, or any other restrictive pulmonary disease 11. Bleeding diathesis or on oral anti-vitamin K medication other than low dose warfarin 12. Pregnancy/lactation 13. Live vaccine required during trial 14. Use of strong inhibitor or inducer of CYP3AE except for anti epileptic drugs 15. Intercurrent infection at time of randomisation 16. Inability to complete study materials (outcome measures) in English 17. History of significant trauma-related cognitive deficit 18. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of Everolimus (e.g. pancreatic insufficiency) 19. Known sensitivity to Everolimus or other Rapamycin analogues or to its excipients 20. Inability to attend scheduled visits |
| Anticipated start date | 01/12/2011 |
| Anticipated end date | 31/12/2013 |
| Status of trial | Ongoing |
| Patient information material | Not available in web format, please use the contact details below to request a patient information sheet |
| Target number of participants | 48 |
| Interventions | RAD001 (Everolimus) versus placebo in the treatment of neurocognitive problems in patients with tuberous sclerosis (TSC) |
| Primary outcome measure(s) |
1. List Learning test (from the BIRT Memory and Information Processing Battery)
2. Complex Figure test (from the BIRT Memory and Information Processing Battery) 3. CANTAB - Stockings of Cambridge (SOC) 4. CANTAB - Spatial Working Memory (SWM) 5. Telephone search dual task (from the Test of Everyday Attention |
| Secondary outcome measure(s) |
1. CANTAB - Rapid Visual Information Processing Battery (RVIP)
2. CANTAB - Spatial Span (SSP) 3. CANTAB - Attentional Set-shifting (IDED) 4. Verbal Fluency /Controlled Oral Word Association Test (COWAT) 5. Cancellation task 6. Symptom Checklist 90R (SCL-90R) 7. Quality of Life in Epilepsy (QOLIE) 8. Liverpool Seizure Severity Scale (LSSS) 9. Vineland Adaptive Behavior Scales-II (VABS-II) (survey form) 10. Social Responsiveness Scale (SRS) 11. Social communication questionnaire (SCQ) |
| Sources of funding | Novartis Pharmaceuticals Ltd (UK) |
| Trial website | |
| Publications | |
| Contact name | Prof Julian Sampson |
| Address |
Institute of Medical Genetics
School of Medicine Cardiff University |
| City/town | Cardiff |
| Zip/Postcode | CF14 4XN |
| Country | United Kingdom |
| Tel | +44 (0)2920 746 412 |
| sampson@cardiff.ac.uk | |
| Sponsor | Cardiff University (UK) |
| Address |
c/o Ms Kathy Pittard Davies
Research and Commercial Division 7th Floor 30 - 36 Newport Road |
| City/town | Cardiff |
| Zip/Postcode | CF24 0DE |
| Country | United Kingdom |
| davieskp2@cardiff.ac.uk | |
| Sponsor website: | http://www.cardiff.ac.uk/ |
| Date applied | 07/11/2011 |
| Last edited | 10/05/2012 |
| Date ISRCTN assigned | 28/12/2011 |
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| © 2012 ISRCTN unless otherwise stated. | |
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