Effects of Methylphenidate on Cellular Abnormalities in Children With Attention Deficit Hyperactivity Disorder (ADHD)

Study Overview
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Brief Summary
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This study will assess the frequency of chromosomal abnormalities measured in circulating lymphocytes in treatment-naive children with Attention Deficit Hyperactivity Disorder (ADHD) treated for 3 months with either extended release methylphenidate or behavioral therapy.

Detailed Description
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This study will determine whether the administration of extended-release methylphenidate in treatment-naïve children with Attention Deficit Hyperactivity Disorder (ADHD) affects the frequency of chromosomal abnormalities.

Official Title
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An Open-label, Behavioral-treatment-controlled Evaluation of the Effects of Extended Release Methylphenidate on the Frequency of Cytogenetic Abnormalities in Children 6 - 12 Years of Age With Attention Deficit Hyperactivity Disorder (ADHD)

Conditions
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Attention Deficit Hyperactivity Disorder

Intervention / Treatment
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* Drug: Extended Release Methylphenidate (Ritalin LA ) plus Behavior Therapy
* Behavioral: Behavior Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children of both genders, 6-12 years old Written informed consent by the parent and the patient (over 7) Diagnosis of ADHD Age-appropriate cognitive functioning All patients who had at least one post-baseline cytogenetic assessment in the core study can enter the observation phase. Exclusion Criteria: History of malignant neoplasm History of seizures (except childhood febrile seizures) Hyperthyroidism Concurrent medical condition which may interfere with study Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Drug: Extended Release Methylphenidate (Ritalin LA ) plus Behavior Therapy<br> <br> * Other names: Ritalin LA;|
| Other: 2<br> | Behavioral: Behavior Therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Chromosomal Aberrations Per 100 Cells Excluding Gaps at Baseline and at the End of Treatment i.e Day 84 (Week 12) | The number of chromosomal aberrations per 100 cells excluding gaps at Baseline (n=33, n=32) and at Week 12 (n=33, n=32) was counted in blood samples cultured for 48 hours using a standard protocol. The types of abnormalities included translocations (reciprocal and non-reciprocal), insertions, dicentrics, fragments, inversions, chromatid exchanges (quadriradials and triradials), breaks, and other unusual observations, eg, aneuploidy, tetraploidy or endoreduplication. | baseline and at end of treatment (Week 12) | 
| The Number of Micronuclei Per 1000 Binucleated Cells Endpoints at Baseline and at the End of Treatment i.e Day 84 (Week 12) | The number of micronuclei per 1000 binucleated cells was measured at Baseline ( n=34 , n=29 ) and at the end of treatment, Week 12 (n =34, n= 29), in blood cultured for 48 hours using a standard protocol. | baseline and at end of treatment (Week 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Sister Chromatoid Exchanges Per Cell | Blood collected at baseline (n=20, n=14) and at the end of treatment, Week 12, (n= 20, n= 14) was cultured for 48 hours using a standard protocol. Giemsa staining and/or fluorescent in situ hybridization (FISH) chromosome painting was done on the cells in metaphase and the number of chromatoid exchanges per cell was recorded by blinded raters. | baseline and at end of treatment (Week 12) | 
| Pharmacokinetic/Pharmacodynamic Relationship of Methylphenidate Blood Levels and Cytogenetic Changes | Since no cytogenetic effects were observed, blood samples were not analyzed for pharmacokinetics/pharmacodynamics. | End of treatment (Week 12) | 
| Change From Baseline to End of Treatment (Week 12) on the Conners' ADHD/DSM-IV Scale for Parents (CADS-P) | Parents completed the Conners' ADHD/DSM-IV Scale for Parents (CADS-P) consisting of the ADHD Index (12 items) and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)( 18 items). Parents rated their child's behavior of the previous week from a list of common problems. When asked How much of a problem has this been in the last week? parents selected 0 = none, not at all, seldom, or very infrequently; 3 = very much true, or it occurs very often or frequently; or 1 or 2 for ratings in between. A score of 50 is considered normal and more than 70 markedly atypical. | Baseline to end of treatment (Week 12) | 
| Change From Baseline to the End of Treatment (Week 12) on the Global Improvement Rating of the Clinical Global Impression Scale (CGI-I) | The Clinical Global Impression scale (CGI-I) is a clinician-rated instrument designed to assess the overall change of illness relative to baseline. The CGI-I consists of 7 ratings as follows: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. CGI-I assessments are relative to the patient's status at the Baseline visit. | From baseline to the end of treatment (Week 12) | 
| Change From Baseline to the End of Treatment (Week 12) on the Severity of Illness Rating of the Clinical Global Impression Scale (CGI-S) | The Clinical Global Impression scale (CGI-S) is a clinician-rated instrument designed to assess the severity of illness. The CGI-S rating indicates illness severity at each time-point on a scale as follows: 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = extremely ill. CGI-S assessments are relative to the patient's status at the Baseline visit. | From baseline to the end of treatment (Week 12) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Attention Deficit Hyperactivity Disorder,, ADHD, Cytogenetic abnormalities,, extended-release methylphenidate,