A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms

• ClinicalTrials.gov Identifier: NCT00541346
• Recruitment Status: Completed
• First Posted: October 10, 2007
• Results First Posted: February 6, 2014
• Last Update Posted: February 6, 2014
• Sponsor: University of Oklahoma
• Collaborator: Mark L. Wolraich, M.D.
• Information provided by (Responsible Party): University of Oklahoma

Study Description

Brief Summary:

This is an open-label study of the efficacy of Daytrana (methylphenidate transdermal system) for the treatment of attention and behavioral symptoms in children with Autism Spectrum Disorders. Twenty patients will be enrolled and treated with 10-30 mg of Daytrana for a total of eight weeks. Changes in core hyperactivity, impulsivity, and inattention symptoms, autism spectrum symptoms and functional outcomes will be assessed. Acceptability of the transdermal route of administration in this population will also be assessed.

The researchers hypothesize that Daytrana is a safe and effective medication for children with Autism Spectrum Disorders who have symptoms of inattention, hyperactivity and impulsivity.

Condition or disease	Intervention/treatment	Phase
Autism; Attention Deficit Hyperactivity Disorder	Drug: Methylphenidate Transdermal System	Phase 3

Detailed Description:

The design will be an open-label trial of eight weeks duration with 20 children with Autism co-morbid for ADHD. The subjects will receive 7 days of 10 mg of Daytrana. The children will be seen weekly for assessment for 4 weeks then every two weeks until the eight week period is complete. After each week of treatment, response will be reassessed and the dose will be increased stepwise to 15 mg, 20 mg, 30 mg unless there are excessive side effects, in which case, the dose will be reduced to the previous dose or the patch wear time may be revised.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase III Study of Autism Co-Morbid for Attention Deficit Hyperactivity Disorder
• Study Start Date: September 2007
• Actual Primary Completion Date: May 2009
• Actual Study Completion Date: February 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: Methylphenidate Transdermal System; 10mg for one week, with weekly stepwise increases to 15mg, 20mg, and 30mg for additional 7 weeks, if symptom reports remained elevated. Titration decreased one stepwise dosage	Drug: Methylphenidate Transdermal System; 10mg for one week, with weekly stepwise increases to 15mg, 20mg, and 30mg for additional 7 weeks, if symptom reports remained elevated. Titration decreased one stepwise dosage; Other Name: Daytrana, MethylPatch, MTS

Outcome Measures

Primary Outcome Measures :

1. Change in Attention Deficit Hyperactivity Disorder Rating Scale - IV (ADHD-RS-IV) Total Score From Baseline to 8-week Follow-up Visit [ Time Frame: Baseline, 8 weeks ]
   This instrument is a parent rating scale used to assess the frequency of ADHD symptoms based on DSM-IV criteria. Raw scores range from 0-54. Higher scores indicate a higher frequency of ADHD symptoms. Raw scores were used in the analyses described below.

Secondary Outcome Measures :

1. Change in Aberrant Behavior Checklist (ABC) Hyperactivity Scores From Baseline to 8-week Follow-up Visit [ Time Frame: Baseline, 8 weeks ]
   The ABC is a behavior rating scale administered by the clinician which is designed to measure behavior changes brought about by drug treatment effects. 16 of these items comprise the hyperactivity, noncompliance factor. Each item is scored on a 3 point scale where 0 indicates the behavior is not a problem and 3 indicates the behavior problem is severe in degree. The minimum score on this factor is 0 (no behavior problems) while the maximum score is 48 ( severe behavior problems).
2. Change in Aberrant Behavior Checklist (ABC) Irritability Scores From Baseline to 8-week Follow-up Visit [ Time Frame: Baseline, 8 weeks ]
   The ABC is a behavior rating scale administered by the clinician which is designed to measure behavior changes brought about by drug treatment effects. 15 of these items comprise the irritability/agitation/crying factor. Each item is scored on a 3 point scale where 0 indicates the behavior is not a problem and 3 indicates the behavior problem is severe in degree. The minimum score on this factor is 0 (no behavior problems) while the maximum score is 45 ( severe behavior problems).
3. Change in Aberrant Behavior Checklist (ABC) Lethargy Scores From Baseline to 8-week Follow-up Visit [ Time Frame: Baseline, 8 weeks ]
   The ABC is a behavior rating scale administered by the clinician which is designed to measure behavior changes brought about by drug treatment effects. 16 of these items comprise the lethargy/social withdrawal factor. Each item is scored on a 3 point scale where 0 indicates the behavior is not a problem and 3 indicates the behavior problem is severe in degree. The minimum score on this factor is 0 (no behavior problems) while the maximum score is 48 ( severe behavior problems).
4. Change in Aberrant Behavior Checklist (ABC) Stereotypy Scores From Baseline to 8-week Follow-up Visit [ Time Frame: Baseline, 8 weeks ]
   The ABC is a behavior rating scale administered by the clinician which is designed to measure behavior changes brought about by drug treatment effects. 7 of these items comprise the stereotypic behavior factor. Each item is scored on a 3 point scale where 0 indicates the behavior is not a problem and 3 indicates the behavior problem is severe in degree. The minimum score on this factor is 0 (no behavior problems) while the maximum score is 21 ( severe behavior problems).
5. Change in Aberrant Behavior Checklist (ABC) Inappropriate Speech Scores From Baseline to 8-week Follow-up Visit [ Time Frame: Baseline, 8 weeks ]
   The ABC is a behavior rating scale administered by the clinician which is designed to measure behavior changes brought about by drug treatment effects. 4 of these items comprise the lethargy/social withdrawal factor. Each item is scored on a 3 point scale where 0 indicates the behavior is not a problem and 3 indicates the behavior problem is severe in degree. The minimum score on this factor is 0 (no behavior problems) while the maximum is 12 ( severe behavior problems).
6. Change in Lifetime Participation Scale (LPS) Total Scores From Baseline to 8-week Follow-up Visit [ Time Frame: Baseline, 8 weeks ]
   The LPS was developed to capture treatment-related improvements in adaptive functioning including quality of life, social development, and emotion regulation. There are 24 items scored using a 4-point Likert frequency scale (0=Never or Seldom, 1=Sometimes, 2=Often, 3=Very Often). A summed scale score (possible range of 0 to 72) was used in the analyses described below. Higher scores indicate more adaptive functioning.
7. Change in Family III General Scale Summed Score From Baseline to 8-week Follow-up Visit [ Time Frame: Baseline, 8 weeks ]
   The Family Assessment measure is a self-report instrument that provides quantitative indices of family strengths and weaknesses. Each items is rated 0 (strongly agree) to 3 (strongly disagree). The General scale produces seven subscales: task accomplishment, role performance, communication, affective expression, involvement, control and values and norms. The minimum score for each subscale is 0 while the maximum score is 15. Higher raw scores indicate a higher number of family problems reported. A total summed score of all scale scores was used in the analyses described below. The possible range of this total score was 0 to 105. Like the subscales, higher values for this total summed score indicate a higher number of family problems reported.
8. Change in Pediatric Evaluation Disability Inventory (PEDI) Caregiver Assistance: Self-Care From Baseline to 8-week Follow-up Visit [ Time Frame: Baseline, 8 weeks ]
   The PEDI Caregiver Assistance measures rate the child's function in three domains: Self-care, Mobility, and Social Function. Items are scored 0 (total, where the child is completely dependent on assistance) to 5 (independent, where no assistance is given or required). Scale scores represent summed item scores within each domain. The Self-Care scale score ranges from 0 to 40. A higher score indicates a higher degree of independence in the self-care area.
9. Change in Pediatric Evaluation Disability Inventory (PEDI) Social Function From Baseline to 8-week Follow-up Visit [ Time Frame: Baseline, 8 weeks ]
   The PEDI Caregiver Assistance measures rate the child's function in three domains: Self-care, Mobility, and Social Function. Items are scored 0 (total, where the child is completely dependent on assistance) to 5 (independent, where no assistance is given or required). Scale scores represent summed item scores within each domain. The Social-Function scale score ranges from 0 to 25. A higher score indicates a higher degree of independence in the Social-Function area.
10. Change in Attention Deficit Hyperactivity Disorder Rating Scale IV: Teacher Assessment Total Scores From Baseline to 8-week Follow-up Visit [ Time Frame: Baseline, 8 weeks ]
    This instrument is a teacher rating scale used to assess the frequency of ADHD symptoms based on DSM-IV criteria. Raw scores range from 0-54. Higher scores indicate a higher frequency of ADHD symptoms. Raw scores were used in the analyses described below.

Eligibility Criteria

• Ages Eligible for Study: 6 Years to 11 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Between 6 and 11 years
• Autism Spectrum Disorder
• Attention Deficit Hyperactivity Disorder
• Stimulant medication-free at study entry
• No clinically significant abnormalities that preclude safe participation
• Sufficient developmental level (~3 yrs)
• Able to keep appointments
• Able to communicate effectively
• Teacher cooperation

Exclusion Criteria:

• Received an investigational medication in the previous 30 days
• Current medication treatment is effective and well-tolerated
• Medical conditions that affect patient safety
• MAOIs within one month
• Hypertension
• Bipolar disorder or psychosis
• Anticonvulsants
• Psychotropic medication or health food supplement
• Tourette Disorder
• Seizure disorder
• Neurological condition
• Structural heart disease

Contacts and Locations

Locations

United States, Oklahoma

OU Child Study Center

Oklahoma City, Oklahoma, United States, 73117

Sponsors and Collaborators

University of Oklahoma

Mark L. Wolraich, M.D.

Investigators

• Principal Investigator: Thomas M Lock, M.D.; OU Child Study Center
• Study Director: Mark L Wolraich, M.D.; OU Child Study Center

More Information

Publications:

Abanilla PK, Hannahs GA, Wechsler R, Silva RR. The use of psychostimulants in pervasive developmental disorders. Psychiatr Q. 2005 Fall;76(3):271-81. Review.

• Responsible Party: University of Oklahoma
• ClinicalTrials.gov Identifier: NCT00541346
• Other Study ID Numbers: SPD485-420-Lock
• First Posted: October 10, 2007
• Results First Posted: February 6, 2014
• Last Update Posted: February 6, 2014
• Last Verified: December 2013

Keywords provided by University of Oklahoma:

Autism; Autism Spectrum Disorders; ADHD

Additional relevant MeSH terms:

Hyperkinesis; Disease; Autistic Disorder; Attention Deficit Disorder with Hyperactivity; Pathologic Processes; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Attention Deficit and Disruptive Behavior Disorders; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Methylphenidate; Central Nervous System Stimulants; Physiological Effects of Drugs; Dopamine Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Dopamine Agents; Neurotransmitter Agents