Attention Deficit Disorder Medication Response Study
| Status: | Completed |
|---|---|
| Conditions: | Psychiatric |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 7 - 11 |
| Updated: | 4/2/2016 |
| Start Date: | June 2006 |
| End Date: | July 2014 |
| Contact: | Heather R. Matheson, B.A. |
| Email: | heather.matheson@cchmc.org |
| Phone: | 513-636-6632 |
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.
(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.
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.
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.
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.
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