NCT01954693Unknown2 期
TRON: A Randomised, Double Blind, Placebo-controlled Study of RAD001 (Everolimus) in the Treatment of Neurocognitive Problems in Tuberous Sclerosis
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- List Learning test (from the BIRT Memory and Information Processing Battery)
研究概览
简要总结
This is a single centre, two-arm, individually randomised, Phase II, double- blind, placebo-controlled trial of RAD001 (Everolimus) versus placebo in the treatment of neurocognitive problems in patients with tuberous sclerosis (TSC). The IMP is a licensed medicine in this patient group but for a different target of effect. The current trial is a proof of principle study for memory and executive function outcomes.
Following an eligibility visit, patients will be scheduled for baseline visit and randomization. They will then be followed up for 6 months undergoing both safety and neurocognitive assessments whilst taking either the placebo or study drug.
48 patients aged 16 to 60 years with tuberous sclerosis (TSC) who have IQ > 60 and a significant deficit in one or more primary outcome measures will be randomly allocated in a ratio of 2:1 to either RAD001 (Everolimus) or Placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 16 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Definite TSC by current clinical criteria (28);
- •Male or female aged 16 to 60 yrs;
- •IQ over 60 by Wechsler Abbreviated Scales of Intelligence (WASI) and able to participate in direct neuropsychological tests;
- •A score falling on, or below, the 5th percentile (approximately equivalent to -1.5 SD) in one or more of the primary outcome measures:
- •Calculated GFR > 60ml/min/1.73m2 except in case of renal impairment associated with TSC complicating kidneys, where a calculated GFR should be ≥30ml/min/1.73m2;
- •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) ;
- •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;
- •If sexually active - negative pregnancy test in females at the time of informed consent, contraception for males and pre-menopausal females on study);
- •Seizure free or stable seizures as defined by no change in type of AEDs in 6 months prior to full recruitment and randomization at baseline. Doses of drugs may have been changed in the 6 months prior to recruitment;
- •Hepatitis B surface antigen negative, Hepatitis C antibody negative.
- •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;
- •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.
排除标准
- •Prior treatment with an mTOR inhibitor;
- •Investigational agent <30 days prior to randomisation;
- •Surgery in last 2 months;
- •Previous brain neurosurgery;
- •Significant haematological abnormality i.e. haemoglobin < 8g/dL, platelets <80,000/mm3, absolute neutrophil count < 1000/mm3);
- •Urine protein/creatinine >0.02g/mmol except in case of renal impairment associated with TSC complication of kidneys, where urine protein/creatinine ratio should be >0.1g/mmol for exclusion;
- •Serum creatinine > 1.5 x ULN except in case of renal impairment associated with TSC complication of kidneys, where serum creatinine should be >300µmol/L for exclusion;
- •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;
- •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;
- •lymphangioleiomyomatosis with FEV1 <70% of predicted, or any other restrictive pulmonary disease;
- •Bleeding diathesis or on oral anti-vitamin K medication other than low dose warfarin;
- •Pregnancy/lactation;
- •Live vaccine required during trial;
- •Use of strong inhibitor of CYP3AE;
- •Use of strong inducer of CYP3AE except for anti epileptic drugs;
- •Intercurrent infection at time of randomisation;
- •Inability to complete study materials (outcome measures) in English;
- •History of significant trauma-related cognitive deficit;
- •Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of Everolimus (e.g. pancreatic insufficiency);
- •Known sensitivity to Everolimus or other Rapamycin analogues or to its excipients;
- •Inability to attend scheduled visits.
研究组 & 干预措施
Everolimus (RAD001)
Experimental
2x2.5mg daily
干预措施: Everolimus (RAD001) (Drug)
Placebo
Placebo Comparator
2x2.5mg daily
干预措施: Placebo (Drug)
结局指标
主要结局
List Learning test (from the BIRT Memory and Information Processing Battery)
时间窗: 6 months
Complex Figure test (from the BIRT Memory and Information Processing Battery)
时间窗: 6 months
CANTAB - Spatial Working Memory (SWM)
时间窗: 6 months
CANTAB - Stockings of Cambridge (SOC)
时间窗: 6 months
Telephone search dual task (from the Test of Everyday Attention)
时间窗: 6 months
次要结局
- CANTAB - Rapid Visual Information Processing Battery (RVIP)(6 months)
- Quality of Life in Epilepsy (QOLIE)(6 months)
- CANTAB - Spatial Span (SSP)(6 months)
- Verbal Fluency /Controlled Oral Word Association Test (COWAT)(6 months)
- Cancellation task(6 months)
- Symptom Checklist 90R (SCL-90R)(6 months)
- CANTAB - Attentional Set-shifting (IDED)(6 month)
- Liverpool Seizure Severity Scale (LSSS)(6 months)
- Vineland Adaptive Behavior Scales-II (VABS-II) (survey form)(6 months)
- Social Responsiveness Scale - Adult version (SRS-A)(6 months)
- Social communication questionnaire (SCQ)(6 months)
- National Adult Reading Test (NART)(6 months)
研究者
Julian Sampson
Professor
Cardiff University
研究点 (1)
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