Attention Deficit Disorder Medication Response Study

This study is currently recruiting participants.
Verified November 2012 by Children's Hospital Medical Center, Cincinnati
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier:
NCT01727414
First received: August 1, 2012
Last updated: November 15, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
ADHD - Inattentive Type
ADHD - Combined Type
Drug: OROS-Methylphenidate
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Medication Response in Children With Predominately Inattentive Type ADHD

Resource links provided by NLM:


Further study details as provided by Children's Hospital Medical Center, Cincinnati:

Primary Outcome Measures:
  • ADHD symptoms [ Time Frame: baseline, week 1, week 2, week 3, week 4 ] [ Designated as safety issue: No ]
    Assessed via parent and teacher-completed Vanderbilt Rating Scales


Secondary Outcome Measures:
  • Clinician Global Impression rating [ Time Frame: baseline, week 1, week 2, week 3, week 4 ] [ Designated as safety issue: No ]
  • Sluggish Cognitive Tempo rating [ Time Frame: baseline, week 1, week 2, week 3, week 4 ] [ Designated as safety issue: No ]
  • ADHD Impairment Ratings [ Time Frame: baseline, wk 1, wk 2, wk 3, wk 4 ] [ Designated as safety issue: No ]
  • Medication side effect ratings [ Time Frame: baseline, wk 1, wk 2, wk 3, wk 4 ] [ Designated as safety issue: Yes ]
  • Biophysical parameters [ Time Frame: baseline, wk 1, wk 2, wk 3, wk 4 ] [ Designated as safety issue: Yes ]
    weight, heart rate, blood pressure

  • Medication continuity and adherence [ Time Frame: one year after ending of medication trial ] [ Designated as safety issue: No ]
  • Family satisfaction with medication trial [ Time Frame: baseline, 1 month, 1 year ] [ Designated as safety issue: No ]
  • Neuropsychological test performance [ Time Frame: baseline, 1 month ] [ Designated as safety issue: No ]
  • math performance [ Time Frame: baseline and 1 month ] [ Designated as safety issue: No ]
  • direct behavioral observations [ Time Frame: baseline and 1 month ] [ Designated as safety issue: No ]

Estimated Enrollment: 165
Study Start Date: June 2006
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Drug: OROS-Methylphenidate
Methylphenidate, capsule, 0mg, 18mg, 27, 36mg, or 54mg 1x/day for 7 days
Drug: OROS-Methylphenidate
capsule; dosages - 18mg, 27mg, 36mg, 54 mg; frequency - each AM; duration - one week for each dose, with each child receiving 3 doses [children < 25 kg receive 18mg, 27mg, 36mg; children > or = to 25kg get 18mg, 36mg, 54mg]
Other Name: concerta
Drug: Placebo
capsule, frequency - each AM, duration - 1 week

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.

  Eligibility

Ages Eligible for Study:   7 Years to 11 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01727414

Contacts
Contact: Heather R. Matheson, B.A. 513-636-6632 heather.matheson@cchmc.org
Contact: Tanya E. Froehlich, MD, MS 513-636-1154 tanya.froehlich@cchmc.org

Locations
United States, Ohio
Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Heather R Matheson, B.A.    513-636-6632    heather.matheson@cchmc.org   
Principal Investigator: Tanya E Froehlich, MD,MS         
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Investigators
Principal Investigator: Tanya E. Froehlich, MS, MD Children's Hospital Medical Center, Cincinnati
  More Information

No publications provided

Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT01727414     History of Changes
Other Study ID Numbers: ADDMedStudy, K23MH083881
Study First Received: August 1, 2012
Last Updated: November 15, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Children's Hospital Medical Center, Cincinnati:
ADHD
Inattention
Methylphenidate
Pharmacogenetics

Additional relevant MeSH terms:
Attention Deficit Disorder with Hyperactivity
Attention Deficit and Disruptive Behavior Disorders
Mental Disorders Diagnosed in Childhood
Mental Disorders
Methylphenidate
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs
Central Nervous System Stimulants
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 15, 2014