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

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)

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.

Study Overview

• Status: Completed
• Conditions: Attention Deficit Hyperactivity Disorder
• Intervention / Treatment: Behavioral: Behavior Therapy; Drug: Extended Release Methylphenidate (Ritalin LA ) plus Behavior Therapy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77007
      • Novartis Pharmaceuticals Investigational site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1	Drug: Extended Release Methylphenidate (Ritalin LA ) plus Behavior Therapy; Other Names: Ritalin LA
Other: 2	Behavioral: Behavior Therapy

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Novartis

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: December 8, 2006
• First Submitted That Met QC Criteria: December 8, 2006
• First Posted (Estimate): December 11, 2006

Study Record Updates

• Last Update Posted (Estimate): May 17, 2011
• Last Update Submitted That Met QC Criteria: April 19, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: ADHD; Attention Deficit Hyperactivity Disorder,; Cytogenetic abnormalities,; extended-release methylphenidate,
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Disease; Congenital Abnormalities; Attention Deficit Disorder with Hyperactivity; Hyperkinesis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Methylphenidate
• Other Study ID Numbers: CRIT124D2201