A randomised, double blind, placebo-controlled study of RAD001 (Everolimus) in the treatment of neurocognitive problems in tuberous sclerosis

Phase 2

Completed

• Conditions: Tuberous sclerosis; Nervous System Diseases

• Registration Number: ISRCTN09739757
• Lead Sponsor: Cardiff University (UK)

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)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-12-28
• Study Completion: 2018-08-06
• Last Update Posted: 10 April 2023

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 38

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

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
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

Study & Design

• Study Type: Interventional
• Study Design: Not specified