Learning Impairments Among Survivors of Childhood Cancer

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

Learning Impairments Among Survivors of Childhood Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00576472
• Other study ID #: MEMFX2
• Secondary ID: R01CA078957U01CA
• Status: Completed
• Phase: Phase 4
• First received: December 17, 2007
• Last updated: February 27, 2014
• Start date: January 2000
• Est. completion date: March 2010

Study information

• Verified date: February 2013
• Source: St. Jude Children's Research Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 469
• Est. completion date: March 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 6 Years to 18 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Brain Neoplasms
• Brain Tumors
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Methylphenidate
Please see detailed description for dosing information and study design.

Locations

Country	Name	City	State
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Duke University Medical Center	Durham	North Carolina
United States	St. Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
St. Jude Children's Research Hospital	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (4)

Conklin HM, Khan RB, Reddick WE, Helton S, Brown R, Howard SC, Bonner M, Christensen R, Wu S, Xiong X, Mulhern RK. Acute neurocognitive response to methylphenidate among survivors of childhood cancer: a randomized, double-blind, cross-over trial. J Pediatr Psychol. 2007 Oct;32(9):1127-39. Epub 2007 Jun 14. — View Citation

Mulhern RK, Khan RB, Kaplan S, Helton S, Christensen R, Bonner M, Brown R, Xiong X, Wu S, Gururangan S, Reddick WE. Short-term efficacy of methylphenidate: a randomized, double-blind, placebo-controlled trial among survivors of childhood cancer. J Clin Oncol. 2004 Dec 1;22(23):4795-803. Erratum in: J Clin Oncol. 2005 Jan 1;23(1):248. — View Citation

Reddick WE, Shan ZY, Glass JO, Helton S, Xiong X, Wu S, Bonner MJ, Howard SC, Christensen R, Khan RB, Pui CH, Mulhern RK. Smaller white-matter volumes are associated with larger deficits in attention and learning among long-term survivors of acute lymphoblastic leukemia. Cancer. 2006 Feb 15;106(4):941-9. — View Citation

Reeves CB, Palmer S, Gross AM, Simonian SJ, Taylor L, Willingham E, Mulhern RK. Brief report: sluggish cognitive tempo among pediatric survivors of acute lymphoblastic leukemia. J Pediatr Psychol. 2007 Oct;32(9):1050-4. Epub 2007 Oct 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Brain White Matter Volume for Patients Versus Sibling Controls	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.	Enrollment to evaluation of MRI, on average 12.8 months.	No
Primary	Brain White Matter Volume for Patients With Acute Lymphoblastic Leukemia Versus Brain Tumors	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.	Enrollment to evaluation of MRI, on average 12.8 months.	No
Primary	Brain White Matter Volume for Treatment Intensity Groups and Sibling Controls	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.	Enrollment to evaluation of MRI, on average 12.8 months.	No
Primary	Change From Methylphenidate (MPH) Home Maintenance Phase Baseline to Completion of Phase as Measured by Conners' Teacher Rating Scale (CTRS: ADHD T Score)	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.	From beginning and at completion of Methylphenidate (MPH) Home Maintenance Phase, on average 16.3 months.	No
Primary	Change From Maintenance Phase Baseline to Completion of Phase as Measured by Conners' Teacher Rating Scale (CTRS: Cognitive Problem T Score)	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	From beginning and at completion of home maintenance phase, on average 16.3 months.	No
Primary	Change From Maintenance Phase Baseline to Completion of Phase as Measured by Conners' Parent Rating Scale (CPRS: ADHD T Score)	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.	From beginning and at completion of home maintenance phase, on average 16.3 months.	No
Primary	Change From Maintenance Phase Baseline to Completion of Phase as Measured by Conner's Parent Rating Scale (CPRS: Cognitive Problem T Score)	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	From beginning and at completion of home maintenance phase, on average 16.3 months.	No
Primary	Change From Maintenance Phase Baseline to Completion of Phase as Measured by Social Skill Rating System (SSRS-P)	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	From beginning and at completion of home maintenance phase, on average 16.3 months.	No
Primary	Change From Maintenance Phase Baseline to Completion of Phase as Measured by Wechsler Individual Achievement Test (WIAT) Reading: Composite Standard Score	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	From beginning and at completion of home maintenance phase, on average 16.3 months.	No
Primary	Change From Maintenance Phase Baseline to Completion of Phase as Measured by Wechsler Individual Achievement Test (WIAT) Spelling: Standard Score	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	From beginning and after completion of home maintenance phase, on average 16.3 months.	No
Primary	Change From Maintenance Phase Baseline to Completion of Phase as Measured by Wechsler Individual Achievement Test (WIAT) Math: Composite Standard Score	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	From beginning and after completion of home maintenance phase, on average 16.3 months.	No
Secondary	Best Weekly Score Measured by Conners' Parent Rating Scale (CPRS: ADHD T Score) During the 3-week Home Crossover Phase.	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.	weekly during 3-week home crossover phase	No
Secondary	Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Parent Rating Scale (CPRS) Cognitive Problem/Inattention Scale.	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.	Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.	No
Secondary	Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Parent Rating Scale (CPRS) Hyperactivity Scale.	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.	Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.	No
Secondary	Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Parent Rating Scale (CPRS) ADHD Index.	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.	Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.	No
Secondary	Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Teacher Rating Scale (CTRS) Cognitive Problem/Inattention Scale.	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.	Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.	No
Secondary	Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Teacher Rating Scale (CTRS) Hyperactivity Scale.	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.	Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.	No
Secondary	Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by The Conners' Teacher Rating Scale (CTRS) ADHD Index.	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.	Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks	No
Secondary	Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by Social Skills Rating System - Parent (SSRS-P) - Social Skill.	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.	Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.	No
Secondary	Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by Social Skills Rating System - Parent (SSRS-P) - Problem Behavior.	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.	Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.	No
Secondary	Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by Social Skills Rating System - Teacher (SSRS-T) - Social Skill.	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.	Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.	No
Secondary	Effectiveness of MPH in Enhancing Classroom Attentiveness, Academic Productivity, and Social Behavior Measured by Social Skills Rating System - Teacher (SSRS-T) - Problem Behavior.	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.	Evaluated at the end of each medication week during the Home Therapy Phase- placebo, low dose and moderate dose weeks.	No
Secondary	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.	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.	Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.	No
Secondary	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.	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.	Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.	No
Secondary	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.	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.	Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.	No
Secondary	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).	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 ß 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.	Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.	No
Secondary	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).	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 ß are derived variables from signal detection theory. ß is a measure of response tendency; higher scores indicate a more conservative response pattern. ß 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.	Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.	No
Secondary	Establish the Effectiveness of MPH on Laboratory Measures of Learning and Recall Using California Verbal Learning Test (CVLT) Over Five Learning Trials.	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.	Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.	No
Secondary	Establish the Effectiveness of MPH on Laboratory Measures of Learning and Recall Using California Verbal Learning Test (CVLT) for Short Delay Free Recall.	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.	Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.	No
Secondary	Establish the Effectiveness of MPH on Laboratory Measures of Learning and Recall Using California Verbal Learning Test (CVLT) for Long Delay Free Recall.	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.	Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.	No
Secondary	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.	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.	Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.	No
Secondary	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.	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.	Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.	No
Secondary	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.	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.	Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.	No
Secondary	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.	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.	Subjects were tested in both the drug and placebo groups before and after taking either MPH or placebo.	No

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