Tuberous sclerosis Nervous System Diseases Tuberous sclerosis
Conditions
Interventions
RAD001 (Everolimus) versus placebo in the treatment of neurocognitive problems in patients with tuberous sclerosis (TSC)
Sponsors
Cardiff University (UK)
Eligibility
Sex/Gender
All
Age
16 Years to 60 Years
Inclusion criteria
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. A score falling on, or below, the 5th percentile (approximately equivalent to -1.5 SD) in one or more of the primary outcome measures (updated 24/04/2019. Previously: Deficit of - 2 S.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
Exclusion criteria
Exclusion criteria: 1. Prior treatment with an mTOR (mammalian target of rapamycin) inhibitor 2. Investigational agent 0.02 g/mmol 7. Serum creatinine > 1.5 x ULN 8. Uncontrolled hyperlipidaemia (fasting cholesterol >300 mg/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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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) | — |
Countries
United Kingdom, Wales
Contacts
Public ContactCheney Drew
Outcome results
None listed