Learning Impairments Among Survivors of Childhood Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00576472
First received: December 17, 2007
Last updated: February 27, 2014
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Acute Lymphoblastic Leukemia
Brain Tumors
Drug: Methylphenidate
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: Learning Impairments Among Survivors of Childhood Cancer

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • Brain White Matter Volume for Patients Versus Sibling Controls [ Time Frame: Enrollment to evaluation of MRI, on average 12.8 months. ] [ Designated as safety issue: No ]
    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.

  • Brain White Matter Volume for Patients With Acute Lymphoblastic Leukemia Versus Brain Tumors [ Time Frame: Enrollment to evaluation of MRI, on average 12.8 months. ] [ Designated as safety issue: No ]
    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.

  • Brain White Matter Volume for Treatment Intensity Groups and Sibling Controls [ Time Frame: Enrollment to evaluation of MRI, on average 12.8 months. ] [ Designated as safety issue: No ]
    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.

  • Change From Methylphenidate (MPH) Home Maintenance Phase Baseline to Completion of Phase as Measured by Conners' Teacher Rating Scale (CTRS: ADHD T Score) [ Time Frame: From beginning and at completion of Methylphenidate (MPH) Home Maintenance Phase, on average 16.3 months. ] [ Designated as safety issue: No ]
    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.

  • Change From Maintenance Phase Baseline to Completion of Phase as Measured by Conners' Teacher Rating Scale (CTRS: Cognitive Problem T Score) [ Time Frame: From beginning and at completion of home maintenance phase, on average 16.3 months. ] [ Designated as safety issue: No ]
    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) [ Time Frame: From beginning and at completion of home maintenance phase, on average 16.3 months. ] [ Designated as safety issue: No ]
    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 Conner's Parent Rating Scale (CPRS: Cognitive Problem T Score) [ Time Frame: From beginning and at completion of home maintenance phase, on average 16.3 months. ] [ Designated as safety issue: No ]
    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 Social Skill Rating System (SSRS-P) [ Time Frame: From beginning and at completion of home maintenance phase, on average 16.3 months. ] [ Designated as safety issue: No ]
    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 [ Time Frame: From beginning and at completion of home maintenance phase, on average 16.3 months. ] [ Designated as safety issue: No ]
    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 Wechsler Individual Achievement Test (WIAT) Spelling: Standard Score [ Time Frame: From beginning and after completion of home maintenance phase, on average 16.3 months. ] [ Designated as safety issue: No ]
    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 [ Time Frame: From beginning and after completion of home maintenance phase, on average 16.3 months. ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Best Weekly Score Measured by Conners' Parent Rating Scale (CPRS: ADHD T Score) During the 3-week Home Crossover Phase. [ Time Frame: weekly during 3-week home crossover phase ] [ Designated as safety issue: No ]
    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 done weekly during the 3-week Home Crossover Period with the best response being used as the measurement for the test.

  • Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Parent Rating Scale (CPRS) Cognitive Problem/Inattention Scale. [ Time Frame: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks. ] [ Designated as safety issue: No ]
    The Conners' Parent Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Three scales are reported: Cognitive Problems/Inattention (assesses the ability to learn at the same pace as peers, organize and complete work, and concentrate for sustained periods of time), Hyperactivity (assesses the ability to sit still to complete tasks, and impulsivity) and ADHD Index (assesses risk for ADHD disorder to be corroborated by other clinical information). 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 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) Hyperactivity Scale. [ Time Frame: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks. ] [ Designated as safety issue: No ]
    The Conners' Parent Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Three scales are reported: Cognitive Problems/Inattention (assesses the ability to learn at the same pace as peers, organize and complete work, and concentrate for sustained periods of time), Hyperactivity (assesses the ability to sit still to complete tasks, and impulsivity) and ADHD Index (assesses risk for ADHD disorder to be corroborated by other clinical information). 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 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) ADHD Index. [ Time Frame: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks. ] [ Designated as safety issue: No ]
    The Conners' Parent Rating Scale- Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Three scales are reported: Cognitive Problems/Inattention (assesses the ability to learn at the same pace as peers, organize and complete work, and concentrate for sustained periods of time), Hyperactivity (assesses the ability to sit still to complete tasks, and impulsivity) and ADHD Index (assesses risk for ADHD disorder to be corroborated by other clinical information). 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 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) Cognitive Problem/Inattention Scale. [ Time Frame: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks. ] [ Designated as safety issue: No ]
    The Conners' Teacher Rating Scale-Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Three scales are reported: Cognitive Problems/Inattention (assesses the ability to learn at the same pace as peers, organize and complete work, and concentrate for sustained periods of time), Hyperactivity (assesses the ability to sit still to complete tasks, and impulsivity) and ADHD Index (assesses risk for ADHD disorder to be corroborated by other clinical information). 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 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. [ Time Frame: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks. ] [ Designated as safety issue: No ]
    The Conners' Teacher Rating Scale-Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Three scales are reported: Cognitive Problems/Inattention (assesses the ability to learn at the same pace as peers, organize and complete work, and concentrate for sustained periods of time), Hyperactivity (assesses the ability to sit still to complete tasks, and impulsivity) and ADHD Index (assesses risk for ADHD disorder to be corroborated by other clinical information). 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 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. [ Time Frame: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks ] [ Designated as safety issue: No ]
    The Conners' Teacher Rating Scale-Revised (S) is a measure of the observed frequency of behaviors associated with ADHD. Three scales are reported: Cognitive Problems/Inattention (assesses the ability to learn at the same pace as peers, organize and complete work, and concentrate for sustained periods of time), Hyperactivity (assesses the ability to sit still to complete tasks, and impulsivity) and ADHD Index (assesses risk for ADHD disorder to be corroborated by other clinical information). 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 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. [ Time Frame: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks. ] [ Designated as safety issue: No ]
    The SSRS assesses social skills for children and adolescents at preschool, elementary and secondary developmental levels. The SSRS is 40 to 57 items, depending on age, completed separately by parents (SSRS-P) and teachers (SSRS-T). Respondents rate the frequency of occurrence for each item ranging from 0 to 2 (0-never, 1-sometimes, 2-very often). The raw scores for the SSRS-P and SSRS-T Social Skills Scales and the SSRS-P and SSRS-T Problem Behaviors Scales have different ranges that are dependent upon age. Raw scores obtained from the SSRS Scales cannot be used to directly interpret social skills or problem behaviors as raw scores vary in meaning based on scale, informant form and developmental level. Raw scores are converted to standard scores with a mean of 100 ± 15. For the Social Skills Scale, a higher score is indicative of better social functioning, and for the Problem Behaviors Scale, a higher score is indicative of greater behavior problems.

  • Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by Social Skills Rating System - Parent (SSRS-P) - Problem Behavior. [ Time Frame: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks. ] [ Designated as safety issue: No ]
    The SSRS assesses social skills for children and adolescents at preschool, elementary and secondary developmental levels. The SSRS is 40 to 57 items, depending on age, completed separately by parents (SSRS-P) and teachers (SSRS-T). Respondents rate the frequency of occurrence for each item ranging from 0 to 2 (0-never, 1-sometimes, 2-very often). The raw scores for the SSRS-P and SSRS-T Social Skills Scales and the SSRS-P and SSRS-T Problem Behaviors Scales have different ranges that are dependent upon age. Raw scores obtained from the SSRS Scales cannot be used to directly interpret social skills or problem behaviors as raw scores vary in meaning based on scale, informant form and developmental level. Raw scores are converted to standard scores with a mean of 100 ± 15. For the Social Skills Scale, a higher score is indicative of better social functioning, and for the Problem Behaviors Scale, a higher score is indicative of greater behavior problems.

  • Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by Social Skills Rating System - Teacher (SSRS-T) - Social Skill. [ Time Frame: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks. ] [ Designated as safety issue: No ]
    The SSRS assesses social skills for children and adolescents at preschool, elementary and secondary developmental levels. The SSRS is 40 to 57 items, depending on age, completed separately by parents (SSRS-P) and teachers (SSRS-T). Respondents rate the frequency of occurrence for each item ranging from 0 to 2 (0-never, 1-sometimes, 2-very often). The raw scores for the SSRS-P and SSRS-T Social Skills Scales and the SSRS-P and SSRS-T Problem Behaviors Scales have different ranges that are dependent upon age. Raw scores obtained from the SSRS Scales cannot be used to directly interpret social skills or problem behaviors as raw scores vary in meaning based on scale, informant form and developmental level. Raw scores are converted to standard scores with a mean of 100 ± 15. For the Social Skills Scale, a higher score is indicative of better social functioning, and for the Problem Behaviors Scale, a higher score is indicative of greater behavior problems.

  • Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by Social Skills Rating System - Teacher (SSRS-T) - Problem Behavior. [ Time Frame: Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks. ] [ Designated as safety issue: No ]
    The SSRS assesses social skills for children and adolescents at preschool, elementary and secondary developmental levels. The SSRS is 40 to 57 items, depending on age, completed separately by parents (SSRS-P) and teachers (SSRS-T). Respondents rate the frequency of occurrence for each item ranging from 0 to 2 (0-never, 1-sometimes, 2-very often). The raw scores for the SSRS-P and SSRS-T Social Skills Scales and the SSRS-P and SSRS-T Problem Behaviors Scales have different ranges that are dependent upon age. Raw scores obtained from the SSRS Scales cannot be used to directly interpret social skills or problem behaviors as raw scores vary in meaning based on scale, informant form and developmental level. Raw scores are converted to standard scores with a mean of 100 ± 15. For the Social Skills Scale, a higher score is indicative of better social functioning, and for the Problem Behaviors Scale, a higher score is indicative of greater behavior problems.

  • 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. [ Time Frame: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo. ] [ Designated as safety issue: No ]
    Change in raw scores for the shortened version of the Conner's CPT from Baseline to Post-dose. The continuous performance test used during the in-lab trial was developed in house using SuperLab Pro v2.0 (Cedrus Corp., Phoenix, AZ). The test was modeled after Conners' CPT, but was shortened for ease of administration and evaluation of short-form sensitivity. The test is one-sixth the length of the Conners' CPT, lasting 2.33 min with 54 total targets and six nontargets (10% of trials). Similar to the Conners' CPT, the interstimulus intervals also varied by trial blocks with lengths of 1, 2, or 4 s. Omission errors are the raw score for the number of targets presented where the subject did not respond. Accordingly, the range for this variable is 0-54 with a higher score indicative of worse performance or problems with sustained attention.

  • 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. [ Time Frame: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo. ] [ Designated as safety issue: No ]
    Change in raw scores for the shortened version of the Conner's CPT from Baseline to Post-dose. The continuous performance test used during the in-lab trial was developed in house using SuperLab Pro v2.0 (Cedrus Corp., Phoenix, AZ). The test was modeled after Conners' CPT, but was shortened for ease of administration and evaluation of short-form sensitivity. The test is one-sixth the length of the Conners' CPT, lasting 2.33 min with 54 total targets and six nontargets (10% of trials). Similar to the Conners' CPT, the interstimulus intervals also varied by trial blocks with lengths of 1, 2, or 4 s. Commission errors are the raw score for the numbers of nontargets presented where the subject incorrectly responded. Accordingly, the range for this variable is 0-6 with a higher score indicative of worse performance or impulsivity.

  • 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. [ Time Frame: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo. ] [ Designated as safety issue: No ]
    Change in raw scores for the shortened version of the Conner's CPT from Baseline to Post-dose. The continuous performance test used during the in-lab trial was developed in house using SuperLab Pro v2.0 (Cedrus Corp., Phoenix, AZ). The test was modeled after Conners' CPT, but was shortened for ease of administration and evaluation of short-form sensitivity. The test is one-sixth the length of the Conners' CPT, lasting 2.33 min with 54 total targets and six nontargets (10% of trials). Similar to the Conners' CPT, the interstimulus intervals also varied by trial blocks with lengths of 1, 2, or 4 s. Hit reaction time is average reaction time in milliseconds for all correct responses when targets were presented. There is no pre-defined range for reaction time; higher score is indicative of slower processing speed.

  • 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). [ Time Frame: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo. ] [ Designated as safety issue: No ]
    Change in raw scores for the shortened version of the Conner's CPT from Baseline to Post-dose. The continuous performance test used during the in-lab trial was developed in house using SuperLab Pro v2.0 (Cedrus Corp., Phoenix, AZ). The test was modeled after Conners' CPT, but was shortened for ease of administration and evaluation of short-form sensitivity. The test is one-sixth the length of the Conners' CPT, lasting 2.33 min with 54 total targets and six nontargets (10% of trials). Similar to the Conners' CPT, the interstimulus intervals also varied by trial blocks with lengths of 1, 2, or 4 s. D' and β are derived variables from signal detection theory. D' is a measure of sensitivity of a person to the signal or target; a higher score is indicative of better performance or better sustained attention. D' was calculated as z(hit) - z(commission). Z-scores were calculated using the NORMSINV function in Microsoft Excel.

  • 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). [ Time Frame: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo. ] [ Designated as safety issue: No ]
    Change in raw scores for the shortened version of the Conner's CPT from Baseline to Post-dose. The continuous performance test used during the in-lab trial was developed in house using SuperLab Pro v2.0 (Cedrus Corp., Phoenix, AZ). The test was modeled after Conners' CPT, but was shortened for ease of administration and evaluation of short-form sensitivity. The test is one-sixth the length of the Conners' CPT, lasting 2.33 min with 54 total targets and six nontargets (10% of trials). Similar to the Conners' CPT, the interstimulus intervals also varied by trial blocks with lengths of 1, 2, or 4 s. D' and β are derived variables from signal detection theory. β is a measure of response tendency; higher scores indicate a more conservative response pattern. β was calculated using the formula = -d'*.5*(NORMSINV(hits)-NORMSINV(false alarms)). In the case where the false alarm rate = 0 or the hit rate = 1.0, we used the standard correction of 1/2N and 1- 1/2N, respectively.

  • Establish the Effectiveness of MPH on Laboratory Measures of Learning and Recall Using California Verbal Learning Test (CVLT) Over Five Learning Trials. [ Time Frame: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo. ] [ Designated as safety issue: No ]
    Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the California Verbal Learning Test (CVLT) to estimate the effectiveness of MPH on laboratory measures of learning and recall. CVLT Trials 1-5 have a mean T Score of 50 and Standard Deviation of 10.

  • Establish the Effectiveness of MPH on Laboratory Measures of Learning and Recall Using California Verbal Learning Test (CVLT) for Short Delay Free Recall. [ Time Frame: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo. ] [ Designated as safety issue: No ]
    Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the California Verbal Learning Test (CVLT) to estimate the effectiveness of MPH on laboratory measures of learning and recall. CVLT Z Score for Short Delay Free Recall has a mean of 0 and a standard deviation of 1.

  • Establish the Effectiveness of MPH on Laboratory Measures of Learning and Recall Using California Verbal Learning Test (CVLT) for Long Delay Free Recall. [ Time Frame: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo. ] [ Designated as safety issue: No ]
    Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the California Verbal Learning Test (CVLT) to estimate the effectiveness of MPH on laboratory measures of learning and recall. CVLT Z Score for Long Delay Free Recall has a mean of 0 and a standard deviation of 1.

  • 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. [ Time Frame: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo. ] [ Designated as safety issue: No ]
    Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the Stroop Word-Color Association Test (Stroop) to estimate the effectiveness of MPH on laboratory measures of interference, impulsivity, cognitive flexibility, and selective attention. Stroop T scores for Word Naming Time have a mean of 50 and a standard deviation of 10.

  • 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. [ Time Frame: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo. ] [ Designated as safety issue: No ]
    Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the Stroop Word-Color Association Test (Stroop) to estimate the effectiveness of MPH on laboratory measures of interference, impulsivity, cognitive flexibility, and selective attention. Stroop T scores for Color Naming Time have a mean of 50 and a standard deviation of 10.

  • 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. [ Time Frame: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo. ] [ Designated as safety issue: No ]
    Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the Stroop Word-Color Association Test (Stroop) to estimate the effectiveness of MPH on laboratory measures of interference, impulsivity, cognitive flexibility, and selective attention. Stroop T scores for Ink Color Naming Time have a mean of 50 and a standard deviation of 10.

  • 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. [ Time Frame: Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo. ] [ Designated as safety issue: No ]
    Patients were randomized into two sequence groups: 1) P/M: placebo followed by MPH; 2) M/P: MPH followed by placebo. We are interested in testing the difference of effects of MPH and placebo, not in testing the difference of two sequence groups. We will use the Stroop Word-Color Association Test (Stroop) to estimate the effectiveness of MPH on laboratory measures of interference, impulsivity, cognitive flexibility, and selective attention. Stroop T scores for Interference Score have a mean of 50 and a standard deviation of 10.


Enrollment: 469
Study Start Date: January 2000
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Drug: Methylphenidate
Please see detailed description for dosing information and study design.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   6 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Glaucoma
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00576472

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
Principal Investigator: Heather M Conklin St. Jude Children's Research Hospital
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00576472     History of Changes
Other Study ID Numbers: MEMFX2, R01CA078957, U01CA081445, P30CA021765
Study First Received: December 17, 2007
Results First Received: October 28, 2011
Last Updated: February 27, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by St. Jude Children's Research Hospital:
Brain Tumor, Acute Lymphoblastic Leukemia, Methylphenidate, Cognitive Late Effects

Additional relevant MeSH terms:
Brain Neoplasms
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Brain Diseases
Central Nervous System Diseases
Central Nervous System Neoplasms
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Nervous System Diseases
Nervous System Neoplasms
Methylphenidate
Central Nervous System Agents
Central Nervous System Stimulants
Dopamine Agents
Dopamine Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014