Effectiveness of an Extended Release Stimulant Medication in Treating Preschool Children With ADHD

Placebo vs. Extended Release Stimulant Crossover Trial in Preschoolers With ADHD

This study will evaluate the safety and effectiveness of extended release mixed amphetamine salts in treating preschool children with attention deficit hyperactivity disorder.

Study Overview

• Status: Completed
• Conditions: Attention Deficit Disorder With Hyperactivity
• Intervention / Treatment: Drug: Sequence 1: XR-MAS then placebo; Drug: Sequence 2 Placebo then XR-MAS

Detailed Description

Attention deficit hyperactivity disorder (ADHD) is a common developmental disorder that affects between 4% and 12% of school-aged children. Children with ADHD often show symptoms of hyperactivity, inattention, inability to sit still, trouble listening, excessive talking, and aggression. ADHD is generally not diagnosed and treated in children less than 6 years old because some symptoms of ADHD are difficult to distinguish from normal behaviors of preschool-aged children. However, some preschool children who exhibit symptoms indicative of ADHD and who have been carefully diagnosed by a health professional may benefit from early treatment to lower risk for functional impairment later in childhood. Currently, environmental changes, parent effectiveness training, and behavior therapy are the commonly used treatments for preschoolers with ADHD symptoms, but not all preschoolers respond well to such behavioral interventions. These children may benefit from medication treatment; however, the safety and effectiveness of ADHD medications in treating preschool-aged children is not well known. Extended release mixed amphetamine salts (XR-MAS), a stimulant medication, is a commonly prescribed and approved medication for treating ADHD in children 6 years and older. Further study is needed to determine how XR-MAS affects preschool-aged children with ADHD symptoms. This study will compare the safety and effectiveness of XR-MAS versus placebo in treating preschool children with ADHD.

Participation in this study will last 6 weeks. All participants will first undergo rigorous psychiatric assessments to confirm their diagnosis of ADHD. Eligible participants will then be assigned randomly to receive treatment with either XR-MAS then placebo or placebo then XR-MAS. Participants will take their assigned XR-MAS or placebo medications for 3 weeks and then cross over to the other medication for an additional 3 weeks of treatment. Rating scale scores will be collected weekly from parents and teachers to assess symptom response and measures of safety.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Living at home for at least 6 months with parent or caregiver
• Enrolled in a structured school setting at least 2 half days a week with a minimum of 7 peers
• Full Scale Intelligence Quotient (FSIQ) of 70 or greater OR 72 or greater if bilingual
• Best estimate diagnosis based on clinical interview, Diagnostic Interview Schedule for Children, Child Behavior Checklist, and rating scales scores
• Symptoms present for at least 9 months
• Meets severity criteria for Clinical Global Impression-Severity with score of greater than or equal to 4 and Clinical Global Assessment Scale score of greater than or equal to 55
• Parent/caregiver can commit to 6 weekly sessions, including initial screening exams
• If on current psychotropic medication, will undergo a washout period of at least 3 days before study entry
• Not currently receiving psychotherapy or started psychotherapy within 30 days of study entry

Exclusion Criteria:

• Previous nonresponse to mixed amphetamine salts (defined as 2 weeks of persistent symptoms in spite of doses greater than or equal to 15 mg per day)
• Diagnosis of language-based or cognitive delay of more than 2 standard deviations below same-aged peers or diagnosis of mental retardation
• Pervasive developmental disorder or autism
• Significant developmental disorder (e.g., blindness, deafness, cerebral palsy, epilepsy, psychosis)
• Taking another psychotropic medication that cannot be discontinued
• Serious psychiatric disorder (e.g., bipolar, suicidality, tic disorder)
• Actively taking medication for certain medical conditions (e.g., hypertension, structural cardiac condition, glaucoma, hyperthyroidism)
• Allergy to mixed amphetamine salts
• History of physical, sexual, or emotional abuse that is clinically significant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence 1: XR-MAS then placebo; Depending on whether 1) child has had previous medication trial or 2) is on psychotropic medication at time of screening, children will either enter the washout period of 3 days before extended release mixed amphetamine salts (XR-MAS) or placebo (PBO) is initiated or proceed directly to the active treatment sequence they were randomized to. Participants randomized to Sequence 1 first receive treatment with XR-MAR for 3 weeks and then placebo for 3 weeks. Flexible, forced dosing will start at 5 mg/day for the first week, increase to 10 mg/day for the second week and continue to 15 mg/day on the third week. No washout period otherwise occurs (XR-MAS is not clinically suspected to have lingering effects beyond initial dosing/day of administration), including the crossover week to PBO.	Drug: Sequence 1: XR-MAS then placebo; XR-MAS given in non-identifying 5 mg capsules with instructions to start 1 capsule (5 mg/d) for one week, then increase to 2 capsules (10 mg/d) for week two, and 3 caps (15 mg/d) for week 3 following flexible, forced titration based on response and tolerance.; Other Names: Adderall XR; IND# 58,037; Drug: Sequence 2 Placebo then XR-MAS; PBO given in non-identifying 5 mg capsules with instructions to start 1 capsule (5 mg/d) for one week, then increase to 2 capsules (10 mg/d) for week two, and 3 caps (15 mg/d) for week 3 following flexible, forced titration based on response and tolerance.
Experimental: Sequence 2 Placebo then XR-MAS; Depending on whether 1) child has had previous medication trial or 2) is on psychotropic medication at time of screening, children will either enter the washout period of 3 days before extended release mixed amphetamine salts (XR-MAS) or placebo (PBO) is initiated or proceed directly to the active treatment sequence they were randomized to. Participants randomized to Sequence 2 will first receive treatment with PBO for 3 weeks and then XR-MAS for 3 weeks. Flexible, forced dosing will start at 5 mg/day for the first week, increase to 10 mg/day for the second week and continue to 15 mg/day on the third week. No washout period (stimulants are not clinically suspected to have lingering effects beyond initial dosing/day of administration)otherwise occurs, including the crossover week to XR-MAS.	Drug: Sequence 1: XR-MAS then placebo; XR-MAS given in non-identifying 5 mg capsules with instructions to start 1 capsule (5 mg/d) for one week, then increase to 2 capsules (10 mg/d) for week two, and 3 caps (15 mg/d) for week 3 following flexible, forced titration based on response and tolerance.; Other Names: Adderall XR; IND# 58,037; Drug: Sequence 2 Placebo then XR-MAS; PBO given in non-identifying 5 mg capsules with instructions to start 1 capsule (5 mg/d) for one week, then increase to 2 capsules (10 mg/d) for week two, and 3 caps (15 mg/d) for week 3 following flexible, forced titration based on response and tolerance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Composite Parent and Teacher Conners Rating Scale Score	Measured weekly for 6 weeks
Tolerance of extended release mixed amphetamine salts	Measured weekly for 6 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Clinical Global Impression- Improvement Score	Measured weekly for 6 weeks

Collaborators and Investigators

• Sponsor: Baystate Medical Center
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: John H. Fanton, MD, Baystate Medical Center

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: July 8, 2008
• First Submitted That Met QC Criteria: July 8, 2008
• First Posted (Estimate): July 10, 2008

Study Record Updates

• Last Update Posted (Estimate): August 23, 2013
• Last Update Submitted That Met QC Criteria: August 10, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: Children; ADHD; Placebo; Medication; Preschool; Controlled Study; Mixed Amphetamine Salts
• Additional Relevant MeSH Terms: Mental Disorders; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Physiological Effects of Drugs; Central Nervous System Stimulants; Adderall
• Other Study ID Numbers: F32MH078388 (U.S. NIH Grant/Contract); DDTR BK-TKFND