Learning Impairments Among Survivors of Childhood Cancer
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 469
- 试验地点
- 3
- 主要终点
- Brain White Matter Volume for Patients Versus Sibling Controls
研究概览
简要总结
Children surviving some types of cancer have a higher risk of developing learning problems after cancer treatment than do children who have not had cancer or its treatment. Cancer treatment may cause problems with learning, attention, and memory. The purpose of this study is to identify brain changes that may underlie learning problems in cancer survivors and investigate whether methylphenidate (a stimulant medication) may reduce these problems.
Subjects who have had treatment for acute lymphoblastic leukemia (ALL) or a brain tumor will be asked to take part in this research study. Siblings of some subjects will also be asked to take part, so that their results can be compared with those of children who have had cancer treatment. We hypothesize that children receiving more aggressive therapy will have lower white matter brain volumes and these volumes will be significantly lower than age-matched siblings. We also hypothesize that children who take methylphenidate will show improvements on teacher and parent report measures of attention and social skills.
详细描述
This study is a multi-phase, multi-site methylphenidate (MPH) trial in childhood cancer survivors. Study participants that meet inclusion and exclusion criteria are screened to ensure that they have adequate global cognitive functioning (IQ > 50) and have academic and attention difficulties that might be managed with MPH. Following the screening phase, qualifying participants take part in a two-day, in-clinic, double-blind, cross-over trial during which they receive MPH (0.6 mg/kg; maximum dose, 20 mg) and placebo (inert substance) in a randomly assigned order. Patients who do not have a significant adverse reaction during the two-day trial go on to participate in a randomized, double-blind, placebo-controlled, three-week home cross-over trial consisting of placebo, low-dose MPH (0.3 mg/kg; maximum dose, 10 mg bid), and moderate-dose MPH (0.6 mg/kg; maximum dose, 20 mg bid). Patients are then selected for participation in a 12-month open-label MPH trial if they show improvement over placebo on a parent and/or teacher rating of attention during the three-week home cross-over trial. The 12-month open-label MPH trial includes individually titrated MPH dosing to maximize clinical benefit, monthly monitoring of side effects and regular acquisition of parent and teacher ratings of attention and behavior. Laboratory measures of intellectual function, attention and memory are conducted at the end of the 12-month trial.
研究设计
- 研究类型
- Interventional
- 干预模型
- Crossover
- 主要目的
- Supportive Care
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 6 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age: 6 to 18 years old.
- •Active subject at St. Jude Children's Research Hospital, or is an age-matched sibling control subject.
- •If a subject, received treatment for brain tumor or ALL with either radiation therapy and/or chemotherapy directed at the brain.
- •If a subject, at least 12 months post-completion of antineoplastic therapies
- •If a subject, no evidence of malignancy, or continuously stable disease since completion of therapy
- •English as a primary language
- •Informed consent
排除标准
- •Patient or immediate family member with a history of Tourette's syndrome
- •Current antidepressant, anxiolytic, antipsychotic or stimulant therapy
- •History of substance abuse
- •Recent history of uncontrolled seizures
- •Uncorrected hypothyroidism
- •Previously or currently randomized on COGRM1 intervention arm
- •Previously diagnosed with ADHD, or, if a patient, diagnosed with ADHD prior to diagnosis of malignancy
研究组 & 干预措施
Treatment
干预措施: Methylphenidate (Drug)
结局指标
主要结局
Brain White Matter Volume for Patients Versus Sibling Controls
时间窗: Enrollment to evaluation of MRI, on average 12.8 months.
To compare the white matter volume of patients with those of sibling controls using MRI results captured between -1.8 and 42.36 months from study enrollment. Existing MRIs very close to enrollment were permissable for inclusion in this study.
Change From Methylphenidate (MPH) Home Maintenance Phase Baseline to Completion of Phase as Measured by Conners' Teacher Rating Scale (CTRS: ADHD T Score)
时间窗: From beginning and at completion of Methylphenidate (MPH) Home Maintenance Phase, on average 16.3 months.
The Conners' Teacher Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Twenty-eight questions are rated on a scale from 0 (not true at all) to 3 (very much true). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed prior to beginning the Methylphenidate (MPH) Home Maintenance Phase(baseline) and upon completion of the phase. Phase completion ranged between 11.44 and 24.36 months.
Brain White Matter Volume for Treatment Intensity Groups and Sibling Controls
时间窗: Enrollment to evaluation of MRI, on average 12.8 months.
To compare the white matter volume of patients by treatment intensity groups (mild, moderate, and high) and sibling controls using MRI results captured between -1.8 and 42.36 months from study enrollment. Existing MRIs very close to enrollment were permissable for inclusion in this study.
Brain White Matter Volume for Patients With Acute Lymphoblastic Leukemia Versus Brain Tumors
时间窗: Enrollment to evaluation of MRI, on average 12.8 months.
To compare the white matter volume of Acute Lymphoblastic Leukemia (ALL) patients with those of patients with malignant brain tumors using MRI results captured between -1.8 and 42.36 months from study enrollment. Existing MRIs very close to enrollment were permissable for inclusion in this study.
Change From Maintenance Phase Baseline to Completion of Phase as Measured by Conners' Teacher Rating Scale (CTRS: Cognitive Problem T Score)
时间窗: From beginning and at completion of home maintenance phase, on average 16.3 months.
The Conners' Teacher Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Twenty-eight questions are rated on a scale from 0 (not true at all) to 3 (very much true). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months
Change From Maintenance Phase Baseline to Completion of Phase as Measured by Conners' Parent Rating Scale (CPRS: ADHD T Score)
时间窗: From beginning and at completion of home maintenance phase, on average 16.3 months.
The Conners' Teacher Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Twenty-seven questions are rated on a scale from 0 (not true at all) to 3 (very much true). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 and 24.36 months.
Change From Maintenance Phase Baseline to Completion of Phase as Measured by Social Skill Rating System (SSRS-P)
时间窗: From beginning and at completion of home maintenance phase, on average 16.3 months.
The Social Skills Rating System- Parent Version (SSRS-P) is a parent rating scale of social behaviors in reference to typically developing children. Thirty eight questions are rated 0 (Never) to 3 (very often). The social skills score is norm-referenced with a mean of 100±15 where a higher score is indicative of better skills. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months
Change From Maintenance Phase Baseline to Completion of Phase as Measured by Wechsler Individual Achievement Test (WIAT) Reading: Composite Standard Score
时间窗: From beginning and at completion of home maintenance phase, on average 16.3 months.
The Wechsler Individual Achievement Test is an examiner administered measure of academic skills. The Reading Composite consists of Basic Reading (single word reading) and Reading Comprehension. Raw scores are converted to standard scores with a mean of 100±15 where higher scores indicate better performance. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months
Change From Maintenance Phase Baseline to Completion of Phase as Measured by Conner's Parent Rating Scale (CPRS: Cognitive Problem T Score)
时间窗: From beginning and at completion of home maintenance phase, on average 16.3 months.
The Conners' Teacher Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Twenty-seven questions are rated on a scale from 0 (not true at all) to 3 (very much true). Raw scores are converted to T scores using age and gender normative data. T scores have a mean of 50 ± 10 where higher scores are indicative of greater problems. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months
Change From Maintenance Phase Baseline to Completion of Phase as Measured by Wechsler Individual Achievement Test (WIAT) Spelling: Standard Score
时间窗: From beginning and after completion of home maintenance phase, on average 16.3 months.
The Wechsler Individual Achievement Test is an examiner administered measure of academic skills. The Spelling score assesses the child's ability to spell words to dictation. Raw scores are converted to standard scores with a mean of 100±15 where higher scores indicate better performance. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months
Change From Maintenance Phase Baseline to Completion of Phase as Measured by Wechsler Individual Achievement Test (WIAT) Math: Composite Standard Score
时间窗: From beginning and after completion of home maintenance phase, on average 16.3 months.
The Wechsler Individual Achievement Test is an examiner administered measure of academic skills. The Math Composite score assesses the child's ability to solve calculation problems (Numerical Operations) and solve applied, word problems (Math Reasoning). Raw scores are converted to standard scores with a mean of 100±15 where higher scores indicate better performance. Assessments were performed prior to beginning the Home Therapy Phase (baseline) and upon completion of the phase. Phase completion ranged between 11.44 to 24.36 months
次要结局
- Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Parent Rating Scale (CPRS) ADHD Index.(Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.)
- Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by Social Skills Rating System - Teacher (SSRS-T) - Social Skill.(Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.)
- Establish the Effectiveness of MPH on Laboratory Measures of Learning and Recall Using California Verbal Learning Test (CVLT) for Long Delay Free Recall.(Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.)
- Establish the Effectiveness of MPH on Laboratory Measures of Interference, Impulsivity, Cognitive Flexibility, and Selective Attention Using the Stroop Word-Color Association Test (Stroop) for Interference Score.(Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.)
- Best Weekly Score Measured by Conners' Parent Rating Scale (CPRS: ADHD T Score) During the 3-week Home Crossover Phase.(weekly during 3-week home crossover phase)
- Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Teacher Rating Scale (CTRS) Cognitive Problem/Inattention Scale.(Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.)
- Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Teacher Rating Scale (CTRS) Hyperactivity Scale.(Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.)
- Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by Social Skills Rating System - Parent (SSRS-P) - Social Skill.(Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.)
- Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Parent Rating Scale (CPRS) Cognitive Problem/Inattention Scale.(Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.)
- Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by Social Skills Rating System - Parent (SSRS-P) - Problem Behavior.(Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.)
- Establish the Effectiveness of MPH on Laboratory Measures of Learning and Recall Using California Verbal Learning Test (CVLT) for Short Delay Free Recall.(Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.)
- Establish the Effectiveness of MPH on Laboratory Measures of Interference, Impulsivity, Cognitive Flexibility, and Selective Attention Using the Stroop Word-Color Association Test (Stroop) for Color Naming Time.(Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.)
- Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Parent Rating Scale (CPRS) Hyperactivity Scale.(Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.)
- Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Teacher Rating Scale (CTRS) ADHD Index.(Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks)
- Establish the Effectiveness of MPH on Laboratory Measures of Sustained Attention, Reaction Time, and, Impulsivity Using Conner's Continuous Performance Test (CPT) for Hit Reaction Time.(Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.)
- Establish the Effectiveness of MPH on Laboratory Measures of Sustained Attention, Reaction Time, and, Impulsivity Using Conner's Continuous Performance Test (CPT) for Beta (Risk Taking).(Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.)
- Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by Social Skills Rating System - Teacher (SSRS-T) - Problem Behavior.(Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.)
- Establish the Effectiveness of MPH on Laboratory Measures of Sustained Attention, Reaction Time, and, Impulsivity Using Conner's Continuous Performance Test (CPT) for Omission Errors.(Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.)
- Establish the Effectiveness of MPH on Laboratory Measures of Sustained Attention, Reaction Time, and, Impulsivity Using Conner's Continuous Performance Test (CPT) for d' (Sensitivity).(Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.)
- Establish the Effectiveness of MPH on Laboratory Measures of Sustained Attention, Reaction Time, and, Impulsivity Using Conner's Continuous Performance Test (CPT) for Commission Errors.(Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.)
- Establish the Effectiveness of MPH on Laboratory Measures of Learning and Recall Using California Verbal Learning Test (CVLT) Over Five Learning Trials.(Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.)
- Establish the Effectiveness of MPH on Laboratory Measures of Interference, Impulsivity, Cognitive Flexibility, and Selective Attention Using the Stroop Word-Color Association Test (Stroop) for Word Naming Time.(Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.)
- Establish the Effectiveness of MPH on Laboratory Measures of Interference, Impulsivity, Cognitive Flexibility, and Selective Attention Using the Stroop Word-Color Association Test (Stroop) for Ink Color Naming Time.(Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.)