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

• ClinicalTrials.gov Identifier: NCT00409708
• Recruitment Status: Completed
• First Posted: December 11, 2006
• Results First Posted: May 17, 2011
• Last Update Posted: May 17, 2011
• Sponsor: Novartis
• Information provided by: Novartis

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Attention Deficit Hyperactivity Disorder	Drug: Extended Release Methylphenidate (Ritalin LA ) plus Behavior Therapy; Behavioral: Behavior Therapy	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 142 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: November 2006
• Actual Primary Completion Date: March 2008

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 1	Drug: Extended Release Methylphenidate (Ritalin LA ) plus Behavior Therapy; Other Name: Ritalin LA
2	Behavioral: Behavior Therapy

Outcome Measures

Primary Outcome Measures :

1. The Number of Chromosomal Aberrations Per 100 Cells Excluding Gaps at Baseline and at the End of Treatment i.e Day 84 (Week 12) [ Time Frame: baseline and at end of treatment (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.
2. The Number of Micronuclei Per 1000 Binucleated Cells Endpoints at Baseline and at the End of Treatment i.e Day 84 (Week 12) [ Time Frame: baseline and at end of treatment (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.

Secondary Outcome Measures :

1. Number of Sister Chromatoid Exchanges Per Cell [ Time Frame: baseline and at end of treatment (Week 12) ]
   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.
2. Pharmacokinetic/Pharmacodynamic Relationship of Methylphenidate Blood Levels and Cytogenetic Changes [ Time Frame: End of treatment (Week 12) ]
   Since no cytogenetic effects were observed, blood samples were not analyzed for pharmacokinetics/pharmacodynamics.
3. Change From Baseline to End of Treatment (Week 12) on the Conners' ADHD/DSM-IV Scale for Parents (CADS-P) [ Time Frame: Baseline to end of treatment (Week 12) ]
   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.
4. Change From Baseline to the End of Treatment (Week 12) on the Global Improvement Rating of the Clinical Global Impression Scale (CGI-I) [ Time Frame: From baseline to the end of treatment (Week 12) ]
   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.
5. Change From Baseline to the End of Treatment (Week 12) on the Severity of Illness Rating of the Clinical Global Impression Scale (CGI-S) [ Time Frame: From baseline to the end of treatment (Week 12) ]
   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Texas

Novartis Pharmaceuticals Investigational site

Houston, Texas, United States, 77007

Sponsors and Collaborators

Novartis

Investigators

• Study Chair: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

• Responsible Party: External Affairs, Novartis
• ClinicalTrials.gov Identifier: NCT00409708
• Other Study ID Numbers: CRIT124D2201
• First Posted: December 11, 2006
• Results First Posted: May 17, 2011
• Last Update Posted: May 17, 2011
• Last Verified: April 2011

Keywords provided by Novartis:

Attention Deficit Hyperactivity Disorder,; ADHD; Cytogenetic abnormalities,; extended-release methylphenidate,

Additional relevant MeSH terms:

Hyperkinesis; Congenital Abnormalities; Disease; Attention Deficit Disorder with Hyperactivity; Pathologic Processes; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Methylphenidate; Central Nervous System Stimulants; Physiological Effects of Drugs; Dopamine Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Dopamine Agents; Neurotransmitter Agents