Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy

Condition(s) targeted: Attention Deficit Disorder With Hyperactivity; Epilepsy

Intervention: Extended Release Methylphenidate (OROS-Methylphenidate) (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: National Institute of Mental Health (NIMH)

Official(s) and/or principal investigator(s):
Joseph M. Gonzalez-Heydrich, MD, Principal Investigator, Affiliation: Children's Hospital Boston, Harvard Medical School

Overall contact:
Joseph M. Gonzalez-Heydrich, MD, Phone: 617-355-6680, Email: joseph.gonzalez-heydrich@childrens.harvard.edu

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.

Official title: Double Blind, Placebo Controlled, Crossover Study of Extended Release Methylphenidate for Treatment of ADHD in Children With Epilepsy

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Safety/Efficacy Study

Primary outcome:

Seizure occurence

Clinical administered scores on the ADHD Rating Scale IV Parent Version

Secondary outcome:

CGI-ADHD-Severity

ADHD Rating Scale IV Teacher Version

Scores on the Barkley Side Effects Checklist-Modified

Clinical Global Impressions (CGI)-ADHD-Improvement

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.

Minimum age: 6 Years. Maximum age: 18 Years. Gender(s): Both.

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.      

Joseph M. Gonzalez-Heydrich, MD, Phone: 617-355-6680, Email: joseph.gonzalez-heydrich@childrens.harvard.edu

Childrens Hospital Boston, Boston, Massachusetts 02115, United States; Recruiting
Joseph M. Gonzalez-Heydrich, MD, Phone: 617-355-6680, Email: joseph.gonzalez-heydrich@childrens.harvard.edu
Jane Whitney, BA, Phone: 617-355-2353, Email: jane.whitney@childrens.harvard.edu

Starting date: May 2003
Ending date: February 2009
Last updated: August 21, 2008