Attention Deficit Disorder With Hyperactivity, Autism
Conditions
Brief summary
This study examined the cognitive and behavioral differences in children who have an autism spectrum disorder (ASD) with or without additional symptoms of ADHD. The study also examined the effectiveness of a range of doses of methylphenidate in improving cognitive and behavioral outcomes in children with both ASD and ADHD.
Detailed description
Attention Deficit Hyperactivity Disorder (ADHD) is a major comorbid psychiatric disorder in children with Autism Spectrum Disorders (ASD) that significantly undermines behavioral, social, and emotional adjustment. Although the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) does not specifically allow for a comorbid diagnosis of ADHD with ASD, many children with an ASD manifest symptoms of ADHD and are treated for it with stimulants or other medication. The few studies on ADHD in ASD have not consistently established its cognitive and behavioral manifestations, or the optimal parameters for treatment. The proposed project will address these issues through studies of cognitive and behavioral functioning in children with ASD, with and without ADHD, and through a study of medication treatment of ADHD symptoms in autism. Participants between the ages of 7 to 12 with an autism spectrum disorder participated in the initial phase of the study to examine the nature and effects of ADHD symptoms on behavioral and cognitive functioning. Participants underwent an initial psychological testing session that included standardized measures of intellectual, adaptive behavior, language, behavioral, and emotional functioning, along with standardized diagnostic measures to confirm their diagnoses of ASD and/or ADHD (Visit 1). Children with intelligence quotients (IQs) below 50 or greater than 130 or with major sensory, motor, neurological, genetic, or psychiatric disorders that may interfere with testing were be excluded. The participants who meet eligibility criteria completed computerized tasks of attentional functioning in a second visit (Visit 2). A subset of the children meeting criteria for the ASD/ADHD group (N=24) participated in a six-week randomized double-blind, placebo-controlled treatment trial using various doses (low, medium, or high dose) of methylphenidate (MPH). Children participated in the treatment trial will be those who qualified based on the initial phase and who do not have any physical contraindications to MPH (e.g., history of MPH intolerance). In each week of the treatment trial, the children took one of the three doses of MPH or a placebo. At the end of each week the child were evaluated in the clinic by including a medical check-up, parent interviews about the child's behavior and functioning that week, and computerized cognitive testing. Additionally, the child's parent and teacher completed questionnaires about the child's behavior each week, so that the child's home and school behaviors at each MPH dose could be assessed.
Interventions
DRUGMethylphenidate-extended release
Methylphenidate-extended release was taken in the morning of the MPH treatment trial. Each participant underwent 1 week of the each of the doses as determined by body weight. The lower body weight group (20 to 24 kg/44 to 52.8 lbs) took 10 mg Ritalin LA to 20 mg. The medium body weight group (25 to 33 kg/55 to 72.6 lbs) took from 10 mg Ritalin LA to 30 mg. The higher body weight group (34 to 59 kg/74.8 to 129.8 lbs) took 20 mg Ritalin LA to 40 mg.
DRUGMethylphenidate-immediate release
Methylphenidate-immediate release was taken in the late afternoon. Each participant underwent 1 week at each of the 3 dose levels as determined by body weight. The lower body weight group (20 to 24 kg/44 to 52.8 lbs) took 2.5 mg IR-MPH and 2 weeks of 5 mg. The medium body weight group (25 to 33 kg/55 to 72.6 lbs) took 2 weeks of 5 mg IR-MPH and 1 week of 10 mg. The higher body weight group (34 to 59 kg/74.8 to 129.8 lbs) took 1 week of 5 mg IR-MPH and 2 weeks of 10 mg.
OTHERPlacebo
Participants will take a placebo for 1 full week of the randomized drug trial. They will take one capsule in the morning and one capsule in the afternoon.
Sponsors
National Institute of Mental Health (NIMH)
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
7 Years to 12 Years
Healthy volunteers
Yes
Inclusion criteria
Autism/ADHD Group: * DSM-IV diagnosis of autistic disorder, as per the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) * Child manifests current symptoms of ADHD Autism/non-ADHD Group: * Meets the diagnostic criteria for autism, as above, but does not meet the diagnostic criteria for ADHD
Exclusion criteria
In both groups,
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Conners' Teacher ADHD Index T Score by Dose | Measured at each dosing week of the drug trial (placebo, low, medium, high) | The ADHD Index of the Conners' Teacher Rating Scale-Revised (CTRS-R) assesses symptoms associated with ADHD, including inattentiveness, hyperactivity and impulsivity. Lower T-scores on this subscale are associated with milder ADHD symptoms. T-scores have a mean of 50 and a SD of 10. Thus, T-scores of 70+ (i.e., 2 SD's over the mean) on the ADHD Index are suggestive of very significant ADHD symptomatology. Treatment-related changes of 5+ points are considered to be significant. |
| Mean Continuous Performance Test (CPT)-Commission Errors by Dose | Measured at each dosing week of the drug trial (placebo, low, medium, high) | CPT is a measure of sustained attention using nonverbal stimuli (pictures). Participants are asked to click on the witch (target), which appears for 25% of the trials. Commission errors are measured by number of times they click for the non-target items. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Conners' Parent ADHD Index T Score by Week | Measured at each dosing week of the drug trial (placebo, low, medium, high) | The ADHD Index of the Conners' Parent Rating Scale-Revised (CPRS-R) assesses symptoms associated with ADHD, including inattentiveness, hyperactivity and impulsivity. Lower T-scores on this subscale are associated with milder ADHD symptoms. T-scores have a mean of 50 and a SD of 10. Thus, T-scores of 70+ (i.e., 2 SD's over the mean) on the ADHD Index are suggestive of very significant ADHD symptomatology. Treatment-related changes of 5+ points are considered to be significant. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from January of 2006 to March of 2010. Sources of recruitment included our UT Department of Psychiatry Clinics, research registry, along with community referrals from local agencies, parent groups, and schools.
Pre-assignment details
129 children completed the initial psychological/screening assessment to confirm study eligibility. Of those 129 children, 94 children met full inclusion/exclusion criteria for the initial phase project. Of these, 28 were invited to participate in the MPH trial and 24 of these children were randomized into the trial.
Participants by arm
| Arm | Count |
|---|---|
| MPH Trial 24 Participants with ASD-ADHD underwent 1 week of placebo, 1 week of Low dose, 1 week of Medium dose, and 1 week of High dose in the MPH treatment phase | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | MPH Trial |
|---|---|
| Age, Categorical <=18 years | 24 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age Continuous | 8.8 years STANDARD_DEVIATION 1.7 |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 24 | 15 / 24 | 17 / 24 | 15 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 |
Outcome results
Primary
Mean Conners' Teacher ADHD Index T Score by Dose
The ADHD Index of the Conners' Teacher Rating Scale-Revised (CTRS-R) assesses symptoms associated with ADHD, including inattentiveness, hyperactivity and impulsivity. Lower T-scores on this subscale are associated with milder ADHD symptoms. T-scores have a mean of 50 and a SD of 10. Thus, T-scores of 70+ (i.e., 2 SD's over the mean) on the ADHD Index are suggestive of very significant ADHD symptomatology. Treatment-related changes of 5+ points are considered to be significant.
Time frame: Measured at each dosing week of the drug trial (placebo, low, medium, high)
Population: Although there were 24 participants who completed the trial, teacher ratings were only available for 18 participants due to 6 children being seen during the summer months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MPH Trial-Placebo Week | Mean Conners' Teacher ADHD Index T Score by Dose | 72.8 Units on a scale (T-scores) | Standard Deviation 12 |
| MPH Trial: Low Dose Week | Mean Conners' Teacher ADHD Index T Score by Dose | 63.1 Units on a scale (T-scores) | Standard Deviation 11.2 |
| MPH Trial: Med Dose Week | Mean Conners' Teacher ADHD Index T Score by Dose | 63.6 Units on a scale (T-scores) | Standard Deviation 10.4 |
| MPH Trial: High Dose Week | Mean Conners' Teacher ADHD Index T Score by Dose | 61.5 Units on a scale (T-scores) | Standard Deviation 13 |
Comparison: Data were analyzed using SPSS-PC repeated measures one-way analysis of variance (ANOVA), with MPH dosing regimen as the within-subjects variable.p-value: =0.001ANOVA
Primary
Mean Continuous Performance Test (CPT)-Commission Errors by Dose
CPT is a measure of sustained attention using nonverbal stimuli (pictures). Participants are asked to click on the witch (target), which appears for 25% of the trials. Commission errors are measured by number of times they click for the non-target items.
Time frame: Measured at each dosing week of the drug trial (placebo, low, medium, high)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MPH Trial-Placebo Week | Mean Continuous Performance Test (CPT)-Commission Errors by Dose | 2.75 Total Errors | Standard Deviation 3.49 |
| MPH Trial: Low Dose Week | Mean Continuous Performance Test (CPT)-Commission Errors by Dose | 1.11 Total Errors | Standard Deviation 1.91 |
| MPH Trial: Med Dose Week | Mean Continuous Performance Test (CPT)-Commission Errors by Dose | 1.18 Total Errors | Standard Deviation 1.71 |
| MPH Trial: High Dose Week | Mean Continuous Performance Test (CPT)-Commission Errors by Dose | 1.24 Total Errors | Standard Deviation 2.27 |
p-value: 0.005ANOVA
Secondary
Mean Conners' Parent ADHD Index T Score by Week
The ADHD Index of the Conners' Parent Rating Scale-Revised (CPRS-R) assesses symptoms associated with ADHD, including inattentiveness, hyperactivity and impulsivity. Lower T-scores on this subscale are associated with milder ADHD symptoms. T-scores have a mean of 50 and a SD of 10. Thus, T-scores of 70+ (i.e., 2 SD's over the mean) on the ADHD Index are suggestive of very significant ADHD symptomatology. Treatment-related changes of 5+ points are considered to be significant.
Time frame: Measured at each dosing week of the drug trial (placebo, low, medium, high)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MPH Trial-Placebo Week | Mean Conners' Parent ADHD Index T Score by Week | 70.1 Units on a scale (T-scores) | Standard Deviation 12 |
| MPH Trial: Low Dose Week | Mean Conners' Parent ADHD Index T Score by Week | 64.9 Units on a scale (T-scores) | Standard Deviation 9.3 |
| MPH Trial: Med Dose Week | Mean Conners' Parent ADHD Index T Score by Week | 62.3 Units on a scale (T-scores) | Standard Deviation 10 |
| MPH Trial: High Dose Week | Mean Conners' Parent ADHD Index T Score by Week | 59.9 Units on a scale (T-scores) | Standard Deviation 10.5 |
p-value: <0.001ANOVA