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Comparing the Effectiveness of New Versus Older Treatments for Attention Deficit Hyperactivity Disorder (The NOTA Study)

Primary Purpose

Attention Deficit Disorder With Hyperactivity

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Methylphenidate transdermal system
Lisdexamfetamine dimesylate
Osmotic-release oral system methylphenidate (OROS MPH)
Mixed amphetamine salts extended release
Sponsored by
Duke University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Attention Deficit Disorder With Hyperactivity focused on measuring ADHD, Methylphenidate, Amphetamine

Eligibility Criteria

6 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Meets DSM-IV diagnostic criteria for ADHD combined, hyperactive/impulsive, or inattentive subtype
  • Outpatient at study entry
  • Speaks English
  • Willing to be randomly assigned to one of the study treatment options as outlined in the protocol
  • No known significant history of cardiovascular disorders, including pre-existing congenital heart disease, structural heart disease, known clinically significant electrocardiogram (ECG) abnormality, or other clinically significant cardiac disorder
  • Willing to initiate study medication for ADHD within 7 days of the study baseline visit
  • May be receiving stable treatment with other drug for a comorbid disorder, defined as no changes in dose or form of drug treatment for at least 2 weeks prior to the study enrollment visit
  • May be receiving psychosocial interventions for ADHD or a comorbid disorder, defined as no changes in form of psychosocial treatment for at least 4 weeks prior to the study enrollment visit

Exclusion Criteria:

  • Hypersensitivity to study medication
  • Inpatient status at study entry
  • Currently taking another medication for ADHD, including another psychostimulant, atomoxetine, or bupropion
  • Receiving treatment with a tricyclic antidepressant at study enrollment, with the exception of low-dose imipramine for enuresis or amitriptyline for chronic pain
  • Received treatment with a monoamine oxidase inhibitor (MAOI) within the past 30 days
  • Psychostimulant drug dependence, bipolar disorder, or schizophrenia
  • Presence of psychosis
  • Severe mental retardation
  • Autism or Asperger's syndrome
  • Active suicidal ideation
  • Unable or unwilling to comply with the protocol
  • Demonstrates a lack of benefit from, an intolerance to, or contraindication to psychostimulant medicine
  • Presence of other clinically significant medical conditions, including hyperthyroidism, epilepsy or other seizure disorder, any condition for which an increase in blood pressure or heart rate would be problematic, glaucoma or other significant eye disease for which a psychostimulant would be problematic, or pre-existing gastrointestinal obstruction with gastrointestinal narrowing
  • Pregnant or positive result of pregnancy test

Sites / Locations

  • Child and Adolescent Psychiatry Trials Network (CAPTN)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

1

2

3

4

Arm Description

Participants will receive methylphenidate transdermal system.

Participants will receive lisdexamfetamine dimesylate.

Participants will receive osmotic-release oral system methylphenidate (OROS MPH).

Participants will receive mixed amphetamine salts extended release.

Outcomes

Primary Outcome Measures

Dichotomized Clinical Global Impression-Effectiveness (CGI-E) Scale
The CGI-E is the value at which the participant's Therapeutic Benefit and Adverse Impact to the study drug intersect. This number is determined by combining each participant's scores for the degree of Therapeutic Benefit versus the degree to which problems with Tolerability and/or Acceptability adversely impact the subject. Participants are then determined to be Responders or Non-responders to the study medication. For example, a subject who is very much improved (CGI-I=1) or much improved (CGI-I=2) therapeutically and whose adverse impact rating is none (score 1,5) or mild (score 2,6) will be categorized as a Responder. All others whose adverse impact rating is moderate (score 3,7,11,15)or outweighs therapeutic effect (score 4,8,12,16) will be categorized as Non-responders to study medication. The CGI scores are totaled for each participant and a mean score is calculated. A median total score was calculated for each treatment group.

Secondary Outcome Measures

Clinical Global Impressions-Improvement (CGI-I) Scale
The CGI-I score at the subject's last study visit at or before Week 6, is one of the 3 secondary endpoints that contribute to the primary endpoint (CGI-E). The CGI-I scale will be used to rate improvement in the subject's condition (benefits) since baseline using the following 7-point scale: 1=very much improved, 2=much improved, 3=minimally improved, 4=not changed, 5=minimally worse, 6=much worse; 7=very much worse.
Clinical Global Improvements-Acceptability (CGI-A) Scale
The CGI-A score at the subject's last study visit at or before Week 6 is one of the 3 secondary endpoints that contribute to the primary endpoint (CGI-E). The CGI-A will be used to assess the acceptability of the study medication with respect to the subject's experience with the formulation of medication. The 7-point rating for the CGI-A will be: 1=very high acceptability, 2=high acceptability, 3=above average acceptability, 4=average acceptability, 5=low acceptability, 6=very low acceptability, 7=extremely low acceptability

Full Information

First Posted
April 27, 2009
Last Updated
July 30, 2013
Sponsor
Duke University
Collaborators
National Institute of Mental Health (NIMH)
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1. Study Identification

Unique Protocol Identification Number
NCT00889915
Brief Title
Comparing the Effectiveness of New Versus Older Treatments for Attention Deficit Hyperactivity Disorder (The NOTA Study)
Official Title
A Randomized Controlled Trial of Methylphenidate Transdermal System (Daytrana), Lisdexamfetamine Dimesylate (Vyvanse), OROS MPH (Concerta), and Mixed Amphetamine Salts Extended Release (Adderall XR) in Children and Adolescents With ADHD
Study Type
Interventional

2. Study Status

Record Verification Date
July 2013
Overall Recruitment Status
Completed
Study Start Date
April 2009 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
December 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
Collaborators
National Institute of Mental Health (NIMH)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study will determine whether two new psychostimulant medications are more effective, tolerable, and acceptable than two older medications for treating attention deficit hyperactivity disorder.
Detailed Description
Attention deficit hyperactivity disorder (ADHD) is characterized by impulsiveness, hyperactivity, and inattention. It is seen primarily in children and adolescents and is often treated with psychostimulant medications. Osmotic-release oral system (OROS) methylphenidate, brand name Concerta, and mixed amphetamine salts extended release, brand name Adderall XR, are psychostimulant medications that have shown both efficacy (that they can have therapeutic benefits) and effectiveness (that they typically have therapeutic benefits in practice). Two newer psychostimulant medications-lisdexamfetamine dimesylate, brand name Vyvanse, and methylphenidate transdermal system, brand name Daytrana-have shown efficacy but have not been tested for effectiveness, nor have they been tested head-to-head against the older psychostimulants. This study will test the effectiveness, tolerability (lack of side effects), and acceptability (ease of use for patients) of the two newer psychostimulant medications and compare them to each other and to the two older psychostimulants. Participation in this study will last 6 weeks, although some treatments may continue past the end of the study. At enrollment, participants will undergo a series of baseline evaluations. These will include interviews and assessments of ADHD symptoms, concurrent psychiatric disorders, medical and psychiatric history, family history of mental illness, risk and protective factors, other treatments, treatment expectancy of both the youth and parent, and vital signs. In consultation with their doctors, participants will be allowed to exclude zero, one, or two of the study medications; if they choose to exclude both of the new ADHD medications, they will not able to participate in the study. Participants will then be randomly assigned to one of the treatments they choose to include. They will receive a prescription for the medication and instructions for how to use it from their doctors; the study protocol does not specify a particular treatment regimen. Participants will undergo a second set of evaluations after 6 weeks of treatment or before, if the treatment ends earlier. This will include interviews and assessments similar to those administered at baseline as well as evaluation of any medication side effects.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Attention Deficit Disorder With Hyperactivity
Keywords
ADHD, Methylphenidate, Amphetamine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
228 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Description
Participants will receive methylphenidate transdermal system.
Arm Title
2
Arm Type
Active Comparator
Arm Description
Participants will receive lisdexamfetamine dimesylate.
Arm Title
3
Arm Type
Active Comparator
Arm Description
Participants will receive osmotic-release oral system methylphenidate (OROS MPH).
Arm Title
4
Arm Type
Active Comparator
Arm Description
Participants will receive mixed amphetamine salts extended release.
Intervention Type
Drug
Intervention Name(s)
Methylphenidate transdermal system
Other Intervention Name(s)
Daytrana
Intervention Description
Not specified in protocol; determined by local standard of care.
Intervention Type
Drug
Intervention Name(s)
Lisdexamfetamine dimesylate
Other Intervention Name(s)
Vyvanse
Intervention Description
Not specified in protocol; determined by local standard of care.
Intervention Type
Drug
Intervention Name(s)
Osmotic-release oral system methylphenidate (OROS MPH)
Other Intervention Name(s)
Concerta
Intervention Description
Not specified in protocol; determined by local standard of care.
Intervention Type
Drug
Intervention Name(s)
Mixed amphetamine salts extended release
Other Intervention Name(s)
Adderall XR
Intervention Description
Not specified in protocol; determined by local standard of care.
Primary Outcome Measure Information:
Title
Dichotomized Clinical Global Impression-Effectiveness (CGI-E) Scale
Description
The CGI-E is the value at which the participant's Therapeutic Benefit and Adverse Impact to the study drug intersect. This number is determined by combining each participant's scores for the degree of Therapeutic Benefit versus the degree to which problems with Tolerability and/or Acceptability adversely impact the subject. Participants are then determined to be Responders or Non-responders to the study medication. For example, a subject who is very much improved (CGI-I=1) or much improved (CGI-I=2) therapeutically and whose adverse impact rating is none (score 1,5) or mild (score 2,6) will be categorized as a Responder. All others whose adverse impact rating is moderate (score 3,7,11,15)or outweighs therapeutic effect (score 4,8,12,16) will be categorized as Non-responders to study medication. The CGI scores are totaled for each participant and a mean score is calculated. A median total score was calculated for each treatment group.
Time Frame
Measured at each participant's last visit, which can occur at or before Week 6
Secondary Outcome Measure Information:
Title
Clinical Global Impressions-Improvement (CGI-I) Scale
Description
The CGI-I score at the subject's last study visit at or before Week 6, is one of the 3 secondary endpoints that contribute to the primary endpoint (CGI-E). The CGI-I scale will be used to rate improvement in the subject's condition (benefits) since baseline using the following 7-point scale: 1=very much improved, 2=much improved, 3=minimally improved, 4=not changed, 5=minimally worse, 6=much worse; 7=very much worse.
Time Frame
Measured at each participant's last visit, which can occur at or before Week 6
Title
Clinical Global Improvements-Acceptability (CGI-A) Scale
Description
The CGI-A score at the subject's last study visit at or before Week 6 is one of the 3 secondary endpoints that contribute to the primary endpoint (CGI-E). The CGI-A will be used to assess the acceptability of the study medication with respect to the subject's experience with the formulation of medication. The 7-point rating for the CGI-A will be: 1=very high acceptability, 2=high acceptability, 3=above average acceptability, 4=average acceptability, 5=low acceptability, 6=very low acceptability, 7=extremely low acceptability
Time Frame
Measured at each participant's last visit, which can occur at or before Week 6

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Meets DSM-IV diagnostic criteria for ADHD combined, hyperactive/impulsive, or inattentive subtype Outpatient at study entry Speaks English Willing to be randomly assigned to one of the study treatment options as outlined in the protocol No known significant history of cardiovascular disorders, including pre-existing congenital heart disease, structural heart disease, known clinically significant electrocardiogram (ECG) abnormality, or other clinically significant cardiac disorder Willing to initiate study medication for ADHD within 7 days of the study baseline visit May be receiving stable treatment with other drug for a comorbid disorder, defined as no changes in dose or form of drug treatment for at least 2 weeks prior to the study enrollment visit May be receiving psychosocial interventions for ADHD or a comorbid disorder, defined as no changes in form of psychosocial treatment for at least 4 weeks prior to the study enrollment visit Exclusion Criteria: Hypersensitivity to study medication Inpatient status at study entry Currently taking another medication for ADHD, including another psychostimulant, atomoxetine, or bupropion Receiving treatment with a tricyclic antidepressant at study enrollment, with the exception of low-dose imipramine for enuresis or amitriptyline for chronic pain Received treatment with a monoamine oxidase inhibitor (MAOI) within the past 30 days Psychostimulant drug dependence, bipolar disorder, or schizophrenia Presence of psychosis Severe mental retardation Autism or Asperger's syndrome Active suicidal ideation Unable or unwilling to comply with the protocol Demonstrates a lack of benefit from, an intolerance to, or contraindication to psychostimulant medicine Presence of other clinically significant medical conditions, including hyperthyroidism, epilepsy or other seizure disorder, any condition for which an increase in blood pressure or heart rate would be problematic, glaucoma or other significant eye disease for which a psychostimulant would be problematic, or pre-existing gastrointestinal obstruction with gastrointestinal narrowing Pregnant or positive result of pregnancy test
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John S. March, MD, MPH
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Child and Adolescent Psychiatry Trials Network (CAPTN)
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States

12. IPD Sharing Statement

Links:
URL
http://dcri.org/
Description
Click here for the Duke Clinical Research Institute Web site
URL
http://www.aacap.org/
Description
Click here for the American Academy of Child and Adolescent Psychiatry Web site

Learn more about this trial

Comparing the Effectiveness of New Versus Older Treatments for Attention Deficit Hyperactivity Disorder (The NOTA Study)

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