Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy - Full Text View

Sponsor:	National Institute of Mental Health (NIMH)
Information provided by:	National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier:	NCT00323947

Purpose

This study will evaluate the safety and effectiveness of extended release methylphenidate (XR-MPH) in treating attention deficit hyperactivity disorder (ADHD) in children with both ADHD and epilepsy.

Condition	Intervention	Phase
Attention Deficit Disorder With Hyperactivity Epilepsy	Drug: Extended Release Methylphenidate (OROS-Methylphenidate)	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Safety/Efficacy Study
Official Title:	Double Blind, Placebo Controlled, Crossover Study of Extended Release Methylphenidate for Treatment of ADHD in Children With Epilepsy

Resource links provided by NLM:

Genetics Home Reference related topics: pyridoxal 5'-phosphate-dependent epilepsy pyridoxine-dependent epilepsy

MedlinePlus related topics: Attention Deficit Hyperactivity Disorder Epilepsy Seizures

Drug Information available for: Methylphenidate Methylphenidate hydrochloride

U.S. FDA Resources

Further study details as provided by National Institute of Mental Health (NIMH):

Primary Outcome Measures:

Seizure occurence [ Time Frame: Measured between Weeks 1 and 4 ] [ Designated as safety issue: Yes ]
Clinical administered scores on the ADHD Rating Scale IV Parent Version [ Time Frame: Measured between Weeks 1 and 4 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

CGI-ADHD-Severity [ Time Frame: Measured between Weeks 1 and 4 ] [ Designated as safety issue: No ]
ADHD Rating Scale IV Teacher Version [ Time Frame: Measured between Weeks 1 and 4 ] [ Designated as safety issue: No ]
Scores on the Barkley Side Effects Checklist-Modified [ Time Frame: Measured between Weeks 1 and 4 ] [ Designated as safety issue: Yes ]
Clinical Global Impressions (CGI)-ADHD-Improvement [ Time Frame: Measured between Weeks 1 and 4 ] [ Designated as safety issue: No ]

Estimated Enrollment:	79
Study Start Date:	May 2003
Estimated Study Completion Date:	February 2009
Estimated Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Participants will take OROS-MPH then switch to placebo	Drug: Extended Release Methylphenidate (OROS-Methylphenidate) Participants will first take either immediate release MPH or placebo "A" for 1 day. On Day 2 of treatment, participants assigned to receive XR-MPH will begin taking it, and participants assigned to receive placebo will switch to placebo "B." This treatment phase will continue for 6 days to 4 weeks, depending on weight, and will then be followed by a 1-week medication washout period. Target dose depends on the weight of the participant. Possible dose forms include 18, 36, 54 mg OROS-MPH.
2: Placebo Comparator Participants will take placebo then switch to OROS-MPH	Drug: Extended Release Methylphenidate (OROS-Methylphenidate) Participants will first take either immediate release MPH or placebo "A" for 1 day. On Day 2 of treatment, participants assigned to receive XR-MPH will begin taking it, and participants assigned to receive placebo will switch to placebo "B." This treatment phase will continue for 6 days to 4 weeks, depending on weight, and will then be followed by a 1-week medication washout period. Target dose depends on the weight of the participant. Possible dose forms include 18, 36, 54 mg OROS-MPH.

Arms

Assigned Interventions

1: Active Comparator

Participants will take OROS-MPH then switch to placebo

Drug: Extended Release Methylphenidate (OROS-Methylphenidate)

Participants will first take either immediate release MPH or placebo "A" for 1 day. On Day 2 of treatment, participants assigned to receive XR-MPH will begin taking it, and participants assigned to receive placebo will switch to placebo "B." This treatment phase will continue for 6 days to 4 weeks, depending on weight, and will then be followed by a 1-week medication washout period. Target dose depends on the weight of the participant. Possible dose forms include 18, 36, 54 mg OROS-MPH.

2: Placebo Comparator

Participants will take placebo then switch to OROS-MPH

Drug: Extended Release Methylphenidate (OROS-Methylphenidate)

Participants will first take either immediate release MPH or placebo "A" for 1 day. On Day 2 of treatment, participants assigned to receive XR-MPH will begin taking it, and participants assigned to receive placebo will switch to placebo "B." This treatment phase will continue for 6 days to 4 weeks, depending on weight, and will then be followed by a 1-week medication washout period. Target dose depends on the weight of the participant. Possible dose forms include 18, 36, 54 mg OROS-MPH.

Detailed Description:

Epilepsy is a brain disorder in which clusters of nerve cells in the brain periodically send abnormal signals. The normal pattern of nerve cell activity, therefore, becomes disrupted, which can result in seizures. Some symptoms of epileptic seizures include the following: strange sensations, emotions, or behavior; convulsions; muscle spasms; and loss of consciousness. Children with epilepsy are at risk for other specific disorders, such as ADHD, one of the most common mental disorders in children. ADHD is characterized by impulsiveness, hyperactivity, and inattention. Approximately one third of children with epilepsy also have ADHD. Stimulant medication is a common treatment method for ADHD. The effect of stimulant treatment on epilepsy and seizure frequency, however, is unknown. This study will evaluate the safety and effectiveness of XR-MPH, a stimulant medication, in treating ADHD in children with both ADHD and epilepsy.

People interested in participating in this double-blind study will first attend two visits for interviews and evaluations to determine eligibility for participation. Upon study entry, participants will be randomly assigned to initially receive either XR-MPH or placebo. Medication dosages and duration in the study will depend on participants' weights. Participants will first take either immediate release MPH or placebo "A" for 1 day. Any participants who experience an adverse event will be removed from the study. On Day 2 of treatment, participants assigned to receive XR-MPH will begin taking it, and participants assigned to receive placebo will switch to placebo "B." This treatment phase will continue for 6 days to 4 weeks, depending on weight, and will then be followed by a 1-week medication washout period. Following the washout, participants will switch to the other treatment group for the remainder of the study and will receive either XR-MPH or placebo in the same manner. Participants will attend weekly study visits, at which they will receive medication and undergo assessments of ADHD symptoms and medication side effects. Blood will be drawn to assess medication levels at the first study visit and following both rounds of treatment. Participants who have trouble with transportation to and from the study site may complete some study visits via telephone. Upon study completion, all participants will be offered clinical treatment with the study physician. Follow-up visits will be held every 2 to 6 months for patients who choose to continue receiving care from the study physician.

Eligibility

Ages Eligible for Study:	6 Years to 18 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Speaks English
IQ of greater than 35 and scores greater than 35 on the Scales of Independent Behavior - Revised (SIB-R) Broad Independence Scale (both IQ and adaptive functioning at the Moderate Mental Retardation level or higher)
Diagnosis of epilepsy by International League Against Epilepsy (ILEA) criteria 26 (repeated, afebrile, unprovoked seizures with a seizure within the past 5 years)
DSM-IV diagnosis of ADHD
Scores at least 4 on the CGI severity scale for ADHD
Scores greater than 90% on the ADHD Rating Scale (ADHD RS), Parent Version; investigator scored for age and sex on either the inattentive, hyperactive-impulsive, or total score at first visit
Has not taken stimulants or alpha-adrenergic medications for more than 2 weeks prior to study entry
If taking antidepressants, neuroleptics, or lithium, doses have been stable for more than 4 weeks
Currently on an antiepileptic drug (AED) regimen with stable doses for more than 4 weeks prior to study entry
Seizure-free for more than 1 month prior to study entry
Prescribing clinician for epilepsy anticipates the need for a stable AED regimen for the duration of the study
Guardian gives permission for study personnel to communicate with prescribing epilepsy clinician
Teacher agrees to fill out ADHD RS at baseline and at the end of each arm of the study

Exclusion Criteria:

Has had a seizure within the month preceding study entry
Change in AED regimen or dose within 4 weeks of study entry
History of moderate or severe adverse event related to MPH
History of any psychotic disorder
Current acute major depression or bipolar mania
Current psychiatric disorder requiring pharmacotherapy (other than ADHD)
Unstable significant medical condition other than epilepsy
Any known conditions that may make treatment with MPH medically inadvisable
Not currently working with a physician for epilepsy treatment
Previously participated in a trial that provided adequate treatment with XR-MPH
Weighs less than 9 kg
Pregnant
Unwilling to use an effective form of contraception
Child has taken a stimulant (MPH, an amphetamine preparation, or pemoline), alpha-adrenergic (clonidine or guanfacine), or other ADHD medication within 2 weeks of the screening telephone interview. Children will not be withdrawn from psychotropic medications in order to be enrolled in the study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00323947

Locations

United States, Massachusetts
Childrens Hospital Boston
Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

National Institute of Mental Health (NIMH)

Investigators

Principal Investigator:

Joseph M. Gonzalez-Heydrich, MD

Children's Hospital Boston, Harvard Medical School

More Information

No publications provided

Responsible Party:	Children's Hospital Boston/Harvard Medical School ( Joseph Gonzalez-Heydrich, MD )
Study ID Numbers:	K23 MH066835, DDTR BK-TKND
Study First Received:	May 8, 2006
Last Updated:	March 9, 2009
ClinicalTrials.gov Identifier:	NCT00323947 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Mental Health (NIMH):

ADHD
Seizures
Methylphenidate
Stimulant

Additional relevant MeSH terms:

Dopamine Uptake Inhibitors
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Methylphenidate
Brain Diseases
Signs and Symptoms
Pathologic Processes
Attention Deficit Disorder with Hyperactivity
Mental Disorders
Therapeutic Uses
Mental Disorders Diagnosed in Childhood

Hyperkinesis
Disease
Nervous System Diseases
Attention Deficit and Disruptive Behavior Disorders
Central Nervous System Diseases
Central Nervous System Stimulants
Dyskinesias
Pharmacologic Actions
Epilepsy
Neurologic Manifestations
Dopamine Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on February 08, 2010