A randomised, double blind, placebo-controlled study of RAD001 (Everolimus) in the TReatment Of Neurocognitive problems in tuberous sclerosis (TRON)

Cardiff University (UK)0 sites38 target enrollmentDecember 28, 2011

ConditionsTuberous sclerosis Nervous System Diseases

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Tuberous sclerosis
Sponsor: Cardiff University (UK)
Enrollment: 38
Status: Completed
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

2016 Protocol article in http://www.ncbi.nlm.nih.gov/pubmed/27515417 protocol 2021 Thesis results in https://orca.cardiff.ac.uk/142676/ (added 14/04/2022)

Registry

who.int

Start Date

December 28, 2011

End Date

August 6, 2018

Last Updated

3 years ago

Study Type

Interventional

Sex

All

Investigators

Sponsor

Cardiff University (UK)

Eligibility 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

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 with the exception of SEGA (sub\-ependymal giant cell astrocytoma) removal surgery or radiosurgery 5 or more years ago (updated on 24/04/2019\. Previously: 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