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

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00409708
First received: December 8, 2006
Last updated: April 19, 2011
Last verified: April 2011
  Purpose

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 Intervention Phase
Attention Deficit Hyperactivity Disorder
Drug: Extended Release Methylphenidate (Ritalin LA ) plus Behavior Therapy
Behavioral: Behavior Therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]
    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.

  • 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) ] [ Designated as safety issue: Yes ]
    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:
  • Number of Sister Chromatoid Exchanges Per Cell [ Time Frame: baseline and at end of treatment (Week 12) ] [ Designated as safety issue: Yes ]
    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.

  • Pharmacokinetic/Pharmacodynamic Relationship of Methylphenidate Blood Levels and Cytogenetic Changes [ Time Frame: End of treatment (Week 12) ] [ Designated as safety issue: No ]
    Since no cytogenetic effects were observed, blood samples were not analyzed for pharmacokinetics/pharmacodynamics.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.


Enrollment: 142
Study Start Date: November 2006
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1 Drug: Extended Release Methylphenidate (Ritalin LA ) plus Behavior Therapy
Other Name: Ritalin LA
2 Behavioral: 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.

  Eligibility

Ages Eligible for Study:   6 Years to 12 Years
Genders Eligible for Study:   Both
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
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: NCT00409708

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

No publications provided

Responsible Party: External Affairs, Novartis
ClinicalTrials.gov Identifier: NCT00409708     History of Changes
Other Study ID Numbers: CRIT124D2201
Study First Received: December 8, 2006
Results First Received: December 6, 2010
Last Updated: April 19, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Attention Deficit Hyperactivity Disorder,
ADHD
Cytogenetic abnormalities,
extended-release methylphenidate,

Additional relevant MeSH terms:
Congenital Abnormalities
Chromosome Aberrations
Chromosome Disorders
Attention Deficit Disorder with Hyperactivity
Hyperkinesis
Pathologic Processes
Genetic Diseases, Inborn
Attention Deficit and Disruptive Behavior Disorders
Mental Disorders Diagnosed in Childhood
Mental Disorders
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Methylphenidate
Central Nervous System Stimulants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014