Tuberous Sclerosis Complex (TSC) MedDRA version: 14.0 Level: PT Classification code 10002649 Term: Anorexia nervosa System Organ Class: 10037175 - Psychiatric disorders
Conditions
Interventions
Trade Name: Afinitor
Product Name: Everolimus
Pharmaceutical Form: Tablet
INN or Proposed INN: Everolimus
CAS Number: 159351-69-6
Sponsors
Cardiff University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Definite TSC by current clinical criteria; 2) Male or female aged 16 to 60 yrs; 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 GFR > 60ml/min/1.73m2; 6) 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) ; 7) 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; 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 AEDs in 6 months prior to recruitment. Doses of drugs may have been changed in the 6 months prior to recruitment; 10) Negative HBV DNA and HCV RNA 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. Are the trial subjects under 18? yes Number of subjects for this age range: 2 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 46 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1) Prior treatment with an mTOR inhibitor; 2) Investigational agent 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, HIV seropositivity, organ transplant, malignancy other than squamous or basal cell skin cancer; 10) Lymphangioleiomyomatosis with 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 |
|---|---|
| Main Objective: The primary objective is to determine how effective Everolimus is compared to a placebo for recall memory (remembering events or information) and executive function (the ability to organise thoughts and activities, prioritise tasks, manage time and make decisions) in people with tuberous sclerosis over a 6 month period.;Secondary Objective: Secondary objectives are to assess the effects of treatment with Everolimus or placebo for 6 months on wider aspects of neurocognitive functioning, seizures and daily life in people with tuberous sclerosis. Also to assess the safety of the study drug using the National Cancer Institute common terminology criteria for adverse event Version 4.0. An additional exploratory objective is to determine whether an effect of treatment with Everolimus or placebo is detectable at 1 month and 3 months after starting therapy to establish whether any early markers of change are present.;Primary end point(s): Primary outcome measures are the following neurological tests and questionnaires; List Learning test (from the BIRT Memory and Information Processing Battery) Complex Figure test (from the BIRT Memory and Information Processing Battery) CANTAB - Stockings of Cambridge (SOC) CANTAB - Spatial Working Memory (SWM) Telephone search dual task (from the Test of Everyday Attention);Timepoint(s) of evaluation of this end point: Following an eligibility visit (Visit 1), patients will be scheduled for baseline visit and randomisation (Visit 2, week 0) and then followed up for 6 months with study visits taking place at week 2 (safety) week 4 (safety, some neurocognition), week 6 (safety), week 12 (full neurocognition) and week 24 (full neurocognition at the end of the treatment phase) within 12 hours after the last drug administration. A further assessment will be carried out 12 weeks after the end of the last drug or placebo administration, at week 36. | — |
Countries
United Kingdom
Outcome results
None listed