Lithium Treatment to Prevent Cognitive Impairment After Brain Radiotherapy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 84
- 试验地点
- 2
- 主要终点
- Processing Speed Index (PSI)
研究概览
简要总结
Randomized, placebo-controlled, double-blinded, parallel group clinical trial to investigate if 6 months of oral lithium tablets (S-lithium 0,5-1,0 mmol/l) will prevent cognitive decline after brain radiotherapy in pediatric brain tumor survivors.
Primary outcome measure is Processing Speed Index (PSI) 2 years after start of study treatment.
详细描述
Late-appearing cognitive side effects after brain radiotherapy is a potential disabling condition in pediatric brain tumor survivors. It can have profound negative effects on education, career options and quality of life. There is no current interventional drug treatment to prevent this intellectual impairment after brain tumor treatment.
Primary objective:
To assess the efficacy of lithium treatment (up to 7 years) after brain radiotherapy (both whole brain and focal) for central nervous system malignancy in preventing late-appearing cognitive processing speed impairment in children aged 5 or older.
Secondary objectives:
- To assess the efficacy of lithium treatment through evaluation of other neuropsychological/quality of life test scores.
- To assess the efficacy of lithium treatment through evaluation of radiological findings after lithium treatment using Magnetic Resonance Imaging (MRI) of the brain.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Identical-looking placebo is used. S-lithium levels are masked by using a separate lab service and sham values for placebo group.
入排标准
- 年龄范围
- 5 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >5 years.
- •Age <18 years at time of radiotherapy.
- •Has received cranial/craniospinal radiation treatment of brain tumor within the last 7 years.
- •Adequate contraceptive method to prevent pregnancy* during the entire lithium treatment period and six months thereafter.
- •Negative pregnancy test* at screening, at start of study treatment, and monthly thereafter.
- •Written informed consent from patient and/or caregiver.
排除标准
- •Allergy/hypersensitivity to lithium or any of the excipients
- •Renal failure (Cystatin C derived Glomerular Filtration Rate < 60).
- •Cardiac failure or heart disease, including Brugada syndrome (or family history thereof).
- •Uncontrolled hypothyroidism.
- •Pregnancy or breast feeding.
- •Severe fluid or electrolyte imbalance.
- •Karnofsky-Lansky score <
- •Other condition deemed incompatible with inclusion in this study (estimated 2 year survival prognosis less than 25 %, expected poor protocol compliance, inability to swallow tablets, language difficulties).
- •Inclusion in other study protocol precluding inclusion in this study.
研究组 & 干预措施
Lithium
Lithionit 42 mg (lithium sulphate, 6 mmol), start dose 1x1, then slow dose escalation using therapeutic drug monitoring (TDI) to establish a target serum level of 0.5-1.0 mmol/liter.
干预措施: Lithium (Drug)
Placebo
Identical looking placebo (white round tablet, 10 mm diameter) will be dose escalated and monitored the same way as lithium, with sham values guiding the dosing.
干预措施: Placebo (Drug)
结局指标
主要结局
Processing Speed Index (PSI)
时间窗: 2 years after start of study treatment
Cognitive processing speed. Normed score min 45, max 155. Higher = better.
次要结局
- Grooved pegboard(Baseline (before treatment) - 5 years after start of study treatment)
- Pediatric QoL Inventory (PedsQL)(Baseline (before treatment) - 5 years after start of study treatment)
- Behavior Rating Inventory of Executive Function (BRIEF).(Baseline (before treatment) - 5 years after start of study treatment)
- Fractional anisotropy (FA) index(Baseline (before treatment) - 5 years after start of study treatment)
- Delis-Kaplan Executive Function System Trail Making Test (D-KEFS TMT)(Baseline (before treatment) - 5 years after start of study treatment)
- University of California Los Angeles (UCLA) 3-Item Loneliness Scale (ULS-3)(Baseline (before treatment) - 5 years after start of study treatment)
- Other Wechsler Intelligence scale scores (except PSI):(Baseline (before treatment) - 5 years after start of study treatment)
- Conner´s Continous Performance Test (CPT) III(Baseline (before treatment) - 5 years after start of study treatment)
- Nepsy II: Inhibition, Verbal Fluency,(Baseline (before treatment) - 5 years after start of study treatment)
- Strengths and Difficulties Questionnaire (SDQ)(Baseline (before treatment) - 5 years after start of study treatment)
- Beery/Buktenica visual motor integration (VMI)(Baseline (before treatment) - 5 years after start of study treatment)
- Delis-Kaplan Executive Function System Color-Word Interference Test (D-KEFS CWT), age 8 years and above.(Baseline (before treatment) - 5 years after start of study treatment)