ADHD - Inattentive TypePhase 4NCT01727414
Attention Deficit Disorder Medication Response Study
A Phase 4 study of ADHD - Inattentive Type and ADHD - Combined Type, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 7 to 11 years
- Conditions the study is for
- ADHD - Inattentive Type, ADHD - Combined Type
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 171 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2006to Jul 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 to 11 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital Medical Center
Cincinnati, Ohio, 45229
About this study
Official title: 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
Read more
- 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.
Read the 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.
- Conditions
- ADHD - Inattentive Type, ADHD - Combined Type
- Being tested
- OROS-Methylphenidate and placebo for inattentive type pts, OROS-Methylphenidate and placebo for combined type pts
- Keywords
- ADHD, Inattention, Methylphenidate, Pharmacogenetics
- Medical subject headings
- Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OROS-Methylphenidate and placebo for inattentive type ptsDrug
Also called concerta
Every participant receives low dose MPH, medium dose MPH, high dose MPH, and placebo for one week each in a triple-blinded fashion.
OROS-Methylphenidate and placebo for combined type ptsDrug
Every participant receives low dose MPH, medium dose MPH, high dose MPH, and placebo for one week each in a triple-blinded fashion.
| Study group | Role | What they receive |
|---|---|---|
| OROS-Methylphenidate and placebo for inattentive type pts | Other | 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. Receives: Drug: OROS-Methylphenidate and placebo for inattentive type pts |
| OROS-Methylphenidate and placebo for combined type pts | Other | 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. Receives: Drug: OROS-Methylphenidate and placebo for combined type pts |
What is being measured
The primary outcome is the main question the study is designed to answer.
Attention Deficit Hyperactivity Disorder Total Symptom Score
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.
Measured: End of placebo dose week, End of low dose week, End of medium dose week , End of high dose week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2012 (estimated)
- Study startJun 2006
- Primary completionJul 2013
- Study completionJul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ADHD - Inattentive TypeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Every participant receives placebo and three different dose of MPH for one week each in a triple blinded fashion
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 171 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Tanya E. Froehlich, MS, MD, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01727414
- Sponsor's protocol ID
- ADDMedStudy
- Other IDs
- K23MH083881
- Status last verified
- Apr 2021
- First submitted
- 1 Aug 2012
- Last updated
- 18 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Froehlich TE, Becker SP, Nick TG, Brinkman WB, Stein MA, Peugh J, Epstein JN. Sluggish Cognitive Tempo as a Possible Predictor of Methylphenidate Response in Children With ADHD: A Randomized Controlled Trial. J Clin Psychiatry. 2018 Mar/Apr;79(2):17m11553. doi: 10.4088/JCP.17m11553.
PubMed 29489078
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Medication Response in Children With Predominately Inattentive Type ADHD
- ClinicalTrials.gov ID
- NCT01727414
- Acronym / sponsor ID
- ADDMedStudy
- Conditions
- ADHD - Inattentive Type, ADHD - Combined Type
- Keywords
- ADHD, Inattention, Methylphenidate, Pharmacogenetics
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 171 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Jun 2006
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 16 Nov 2012 (estimated)
- Results
- Posted 18 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Every participant receives placebo and three different dose of MPH for one week each in a triple blinded fashion
| Arm | Type | Receives |
|---|---|---|
| OROS-Methylphenidate and placebo for inattentive type pts | Other | Drug: OROS-Methylphenidate and placebo for inattentive type ptsChildren 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. |
| OROS-Methylphenidate and placebo for combined type pts | Other | Drug: OROS-Methylphenidate and placebo for combined type ptsChildren 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. |
Who may qualify
- Ages
- 7 to 11 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OROS-Methylphenidate and placebo for inattentive type ptsAlso: concertaEvery 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 |
| OROS-Methylphenidate and placebo for combined type ptsEvery 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 |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29489078Froehlich TE, Becker SP, Nick TG, Brinkman WB, Stein MA, Peugh J, Epstein JN. Sluggish Cognitive Tempo as a Possible Predictor of Methylphenidate Response in Children With ADHD: A Randomized Controlled Trial. J Clin Psychiatry. 2018 Mar/Apr;79(2):17m11553. doi: 10.4088/JCP.17m11553.
- Individual participant dataSharing planned: Undecided
Related trials for ADHD - Inattentive Type
RecruitingPhase 2
Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
Neurodevelopmental Disorders, Autism
Recruiting
A Therapist Guided Internet-delivered Treatment for Adults With ADHD (Attention Deficit / Hyperactivity Disorder) - an Open Effectiveness Trial in Routine Care
ADHD, ADHD - Combined Type
Recruiting
NeuroTrainer Cognitive Training For Academic Focus
ADHD - Combined Type, ADHD Predominantly Inattentive Type
Not yet recruiting
The Primary Objective of This Study is to Determine Whether Positively Framed Information (PFI) on Side Effects, Compared to Negatively Framed and Extensive Information (NFI) Can Reduce the Number and Severity of Reported Adverse Events Caused by ADHD Medication in Children Aged 7 to 17 Years.
Attention Deficit Disorder, Attention Deficit Disorder (ADD)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tanya E. Froehlich, MS, MD principal investigator
Children's Hospital Medical Center, Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study of ADHD - Inattentive Type and ADHD - Combined Type, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01727414, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2021.