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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00889915
First received: April 27, 2009
Last updated: July 30, 2013
Last verified: July 2013

April 27, 2009
July 30, 2013
April 2009
December 2009   (final data collection date for primary outcome measure)
Dichotomized Clinical Global Impression-Effectiveness (CGI-E) Scale [ Time Frame: Measured at each participant's last visit, which can occur at or before Week 6 ] [ Designated as safety issue: No ]
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.
Dichotomized Clinical Global Impression-Effectiveness (CGI-E) scale [ Time Frame: Measured at each participant's last visit, which can occur at or before Week 6 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00889915 on ClinicalTrials.gov Archive Site
  • Clinical Global Impressions-Improvement (CGI-I) Scale [ Time Frame: Measured at each participant's last visit, which can occur at or before Week 6 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Measured at each participant's last visit, which can occur at or before Week 6 ] [ Designated as safety issue: No ]
    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
  • Clinical Global Impressions-Improvement (CGI-I) scale [ Time Frame: Measured at each participant's last visit, which can occur at or before Week 6 ] [ Designated as safety issue: No ]
  • Clinical Global Improvements-Acceptability (CGI-A) scale [ Time Frame: Measured at each participant's last visit, which can occur at or before Week 6 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Comparing the Effectiveness of New Versus Older Treatments for Attention Deficit Hyperactivity Disorder (The NOTA Study)
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

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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Attention Deficit Disorder With Hyperactivity
  • Drug: Methylphenidate transdermal system
    Not specified in protocol; determined by local standard of care.
    Other Name: Daytrana
  • Drug: Lisdexamfetamine dimesylate
    Not specified in protocol; determined by local standard of care.
    Other Name: Vyvanse
  • Drug: Osmotic-release oral system methylphenidate (OROS MPH)
    Not specified in protocol; determined by local standard of care.
    Other Name: Concerta
  • Drug: Mixed amphetamine salts extended release
    Not specified in protocol; determined by local standard of care.
    Other Name: Adderall XR
  • Active Comparator: 1
    Participants will receive methylphenidate transdermal system.
    Intervention: Drug: Methylphenidate transdermal system
  • Active Comparator: 2
    Participants will receive lisdexamfetamine dimesylate.
    Intervention: Drug: Lisdexamfetamine dimesylate
  • Active Comparator: 3
    Participants will receive osmotic-release oral system methylphenidate (OROS MPH).
    Intervention: Drug: Osmotic-release oral system methylphenidate (OROS MPH)
  • Active Comparator: 4
    Participants will receive mixed amphetamine salts extended release.
    Intervention: Drug: Mixed amphetamine salts extended release
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
228
December 2009
December 2009   (final data collection date for primary outcome measure)

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
Both
6 Years to 17 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00889915
Pro00014075, P30MH066386-02, DSIR CTM 4571; Pro00014075
Yes
Duke University
Duke University
National Institute of Mental Health (NIMH)
Principal Investigator: John S. March, MD, MPH Duke University School of Medicine
Duke University
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP