Attention Deficit Disorder Medication Response Study

April 28, 2021 updated by: Children's Hospital Medical Center, Cincinnati

Medication Response in Children With Predominately Inattentive Type ADHD

This study evaluates how children with Attention Deficit Disorder without Hyperactivity (ADD) respond to medication, and if their response is different from children who have problems with both hyperactivity and inattention. In order to do this, children ages 7-11 whose primary difficulty is with attention problems and who have never been on behavioral or psychiatric medications are being recruited. Once enrolled, children will try one week each of 3 different doses of methylphenidate, the most commonly prescribed Attention Deficit, Hyperactivity Disorder (ADHD) medication, as well as placebo. Children will be randomly assigned to one of six possible medication dose and placebo titration schedules, but the study doctor, family, and teacher will not know which dose (if any) children are receiving for a given week. Each week, behavioral and side effect ratings will be completed by both the child's parent and teacher, and the family will meet with the study doctor for a physical examination and to discuss how each week went. Some children will also have neuropsychological testing to determine how methylphenidate influences their working memory, sustained attention, and ability to inhibit (stop) inappropriate responses.

All data will be analyzed to decide which medication dose the child responded to best and further recommendations for treatment will be given. Ultimately, this study aims to improve understanding of how children with ADHD-Primarily Inattentive Type respond to stimulant medications by

  • determining whether these children experience a diminished response to methylphenidate compared to children with both hyperactivity and inattention
  • determining whether certain genetic and environmental factors play a role in this response.

Findings from this study will be used to help streamline the identification of the most effective doses of medication for children with ADHD-Primarily Inattentive Type.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Robust data indicate that stimulant medications reduce ADHD symptoms and impairment, but it is unclear whether their efficacy generalizes across the ADHD subtypes. Although predominately inattentive type (PIT) is the most prevalent ADHD subtype in U.S. population-based studies, few studies have specifically examined response to stimulants in this subtype. Instead, medication guidelines for PIT have largely been extrapolated from studies enrolling all or mostly ADHD-combined type (CT). Thus, this application seeks to improve understanding of stimulant medication response and its predictors in children with PIT. We will evaluate participants' response to methylphenidate (MPH), the most widely prescribed stimulant, via a prospective, double-blind, placebo-controlled crossover trial with 3 dose conditions. Our first specific aim is to examine MPH medication and dose response in children with PIT (n=120) and CT (n=45) to test the hypotheses that participants with PIT have a diminished MPH response and derive less benefit from higher doses compared to those with CT. Since only one prior study has examined genetic predictors of MPH response variability within PIT-only samples, our second specific aim (exploratory) is to determine the potential role of genetic polymorphisms (e.g., those in DAT1, DRD4, NET, ADRA2A, COMT, SNAP25, CES1, GRM7, LPHN3) on MPH response in children with PIT (n=120), examining both symptom change with MPH and MPH dose response curves. If we identify significant differences in MPH response between the subtypes, our findings may guide clinical practice by suggesting more effective medication strategies (such as different dosing schedules) for children with PIT. In addition, this study may yield pharmacogenetic findings that, in the future, could enable physicians to tailor individual treatment plans for children with PIT, ameliorating the current prolonged and expensive practice of prescribing by trial and error.

Study Type

Interventional

Enrollment (Actual)

171

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Children's Hospital Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 years to 9 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Consent: The family must provide signature of informed consent by a parent or legal guardian. Children must also assent to study participation.
  • Age at Screening:7.0 years to 11.9 years, inclusive.
  • Sex: Includes male and female children.
  • ADHD Diagnostic Status: Meets DSM-IV criteria for ADHD, Predominantly Inattentive or Combined subtype with Clinical Global Impression-Severity rating corresponding to at least "moderately ill."
  • Cognitive Functioning-Intelligence Quotient (IQ) of greater than 80 as estimated by Vocabulary and Block Design subtests of the Wechsler Intelligence Scale for Children--4th Edition, or an Intelligence Quotient (IQ) of 80 or greater when administered the Full Scale Version of the Wechsler Intelligence Scale for Children-4th Edition.
  • Absence of Learning Disability:On the abbreviated Wechsler Individual Achievement Test-2nd edition Reading and Math subtests, participants must score above 80. However, children may also be included if they receive a score of 75 or greater on the Word Reading and/or Math subtests, as long as this score is not a significant discrepancy from their full-scale IQ score (e.g., a difference of greater than one standard deviation or 15 points).
  • School: Enrolled in a school setting rather than a home-school program.

Exclusion Criteria:

  • Understanding Level: Participant and/or parent cannot understand or follow study instructions.
  • Psychiatric Medications: Current or prior history of taking any medication for psychological or psychiatric problems.
  • Behavioral Interventions: Current active participation in ADHD-related behavioral interventions or counseling.
  • Exclusionary Psychiatric Conditions: Children with mania/hypomania and/or schizophrenia will be excluded. The following comorbid diagnoses will not be excluded unless they are determined to be the primary cause of ADHD symptomatology (see below for description of this decision process): Post Traumatic Stress Disorder, Phobias and Anxiety Disorders, Obsessive Compulsive Disorder, Major Depression / Dysthymia, Eating Disorders, Elimination Disorders, Trichotillomania, Tic Disorder, Oppositional Defiant Disorder, Conduct Disorder.
  • Organic Brain Injury: History of head trauma, neurological disorder, or other organic disorder affecting brain function.
  • Cardiovascular Risk Factors: Children with a personal history or family history of cardiovascular risk factors will be excluded, or given the option of participating in the study after obtaining an EKG and a signed letter from a pediatric cardiologist verifying the safety of their participation in a trial of methylphenidate. In this case, families will be responsible for the costs of EKG and cardiologist evaluation. If for any reason a family is unable to assume the cost of the EKG and cardiologist evaluations but still wishes for their child to participate, study staff will determine on a case-by-case basis whether the study budget allows the study to offer financial assistance to the families for these evaluations.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: OROS-Methylphenidate and placebo for inattentive type pts
Children with ADHD-inattentive type. Every participant receives low dose MPH, medium dose MPH, high dose MPH, and placebo for one week each in a triple-blinded fashion.
Drug: OROS-Methylphenidate and placebo for inattentive type pts
Every participant receives low dose MPH, medium dose MPH, high dose MPH, and placebo for one week each in a triple-blinded fashion.
Other Names:
  • concerta
Other: OROS-Methylphenidate and placebo for combined type pts
Children with ADHD-combined type type. Every participant receives low dose MPH, medium dose MPH, high dose MPH, and placebo for one week each in a triple-blinded fashion.
Drug: OROS-Methylphenidate and placebo for combined type pts
Every participant receives low dose MPH, medium dose MPH, high dose MPH, and placebo for one week each in a triple-blinded fashion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Attention Deficit Hyperactivity Disorder Total Symptom Score
Time Frame: End of placebo dose week, End of low dose week, End of medium dose week , End of high dose week

Assessed via parent and teacher Vanderbilt Attention Deficit Hyperactivity Disorder Rating Scales which were completed each the 4 weeks of the titration trial.

Range: min=0, max=54 [sum of 18 symptom items, rated from 0 (none), 1 (occasionally), 2 (often), 3 (very often)], higher scores indicate worse outcomes.

Note to address Review Comment: During the 4 week titration trial, the placebo condition and each of the three active dosages (low, medium, and high) were given for one week each. Because the placebo and active dosages were given in random order to preserve the triple blind, all participants did not receive the same order of dosages and it is not possible to connect the dosages (placebo, low dose MPH, medium dose MPH, high dose MPH) to a specific week number (week 1, week 2, week 3, week 4) which would hold for ALL participants. That is why Timeframe was revised from "week 1, week 2, week 3, week 4" to placebo, low dose, medium dose, and high dose week.
End of placebo dose week, End of low dose week, End of medium dose week , End of high dose week

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital Medical Center, Cincinnati

Collaborators

National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Tanya E. Froehlich, MS, MD, Children's Hospital Medical Center, Cincinnati

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2006

Primary Completion (Actual)

July 1, 2013

Study Completion (Actual)

July 1, 2014

Study Registration Dates

First Submitted

August 1, 2012

First Submitted That Met QC Criteria

November 15, 2012

First Posted (Estimate)

November 16, 2012

Study Record Updates

Last Update Posted (Actual)

May 18, 2021

Last Update Submitted That Met QC Criteria

April 28, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ADDMedStudy
  • K23MH083881 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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