Autism Spectrum Disorders
Conditions
Keywords
Autistic Disorder, Asperger's Disorder, Pervasive Developmental Disorder
Brief summary
This study will determine the effectiveness of mirtazapine in reducing anxiety in children with autistic disorder, Asperger's disorder and Pervasive Developmental Disorder.
Detailed description
One of the areas receiving very little attention in Pervasive Developmental Disorders (PDDs) is that of anxiety. Anxiety is common in PDD, but has not yet been fully characterized. The primary objective of this study is to conduct a preliminary placebo-controlled trial of mirtazapine for the treatment of anxiety associated with PDDs. We hypothesize that mirtazapine will be safe and well tolerated.
Interventions
DRUGPlacebo
Subjects randomized to placebo will receive placebo for duration of the study
DRUGMirtazapine
Subjects will receive 7.5 mg daily at the start of the trial. The dose will be increased by 7.5 mg per week for subjects weighing less than 50 kg and up to 15 mg per week for subjects weighing more than 50 kg depending on efficacy and tolerability.
Sponsors
Autism Speaks
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Ages 5-17 years * Diagnosis of autistic disorder, Asperger's disorder or Pervasive Developmental Disorder Not Otherwise Specified (PDD NOS) * Clinically significant anxiety as evidenced by a Pediatric Anxiety Rating Scale (PARS) score of 10 or greater * Abbreviated intelligence quotient (IQ) greater than 50 on the Stanford Binet 5th Ed.
Exclusion criteria
* Diagnosis of Rett's disorder or childhood integrative disorder * Diagnosis of obsessive-compulsive disorder (OCD), post-traumatic stress disorder, major mood disorder, psychotic disorder, or substance use disorder * Presence of any past or present medical conditions that would make treatment with mirtazapine unsafe * Use of other antidepressants or benzodiazepines * Use of other psychotropic medications which are ineffective, poorly tolerated, or sub-optimal in terms of dose * Previous adequate trial of mirtazapine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean 10-Week Change in Pediatric Anxiety Rating Scale 5-Item Total Score, Double-blind Phase | Weeks Baseline, 2, 4, 6, and 10 | The Pediatric Anxiety Rating Scale (PARS) is a clinician-rated instrument that assesses anxiety symptoms that are commonly associated with social anxiety, separation anxiety, and generalized anxiety disorders. Scaled score ranges form 0-25 with higher scores indicating more severe anxiety symptoms. Means were estimated using a repeated measures linear regression model with treatment group, study week (in categories), and their interaction as covariates, and assuming a common mean between treatment groups at baseline. Confidence intervals reflect a Bonferroni multiple testing correction accounting for the selection of two primary outcomes. |
| Proportion of Participants Who Responded to Treatment at 10 Weeks According to the Improvement Item of the Clinical Global Impression-Scale (Response Defined as CGI-I=1 or CGI-I=2) | Screen (Visit 1) Baseline (Visit 2) and Endpoint (Week 10) | The Clinical Global Impressions Global Improvement (CGI-I) is designed to take into account all factors to arrive at an assessment of response to treatment. The CGI-I scale ranges from 1 to 7 (1=very much improved; 2= much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse), with lower scores indicating improvement (1=very much improved and 2=much improved). In this study the CGI was focused on the target symptom of anxiety. Participants with a CGI-I score of 1 or 2 were classified as responders. The CGI-I was administered biweekly for 6 weeks and again at 10 weeks during the study. The participant who withdrew from the study before 10 weeks was not included in the calculations. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mirtazapine The starting dose for subjects is 7.5 mg daily. The maximum daily dose will be 45 mg.
Mirtazapine: Subjects will receive 7.5 mg daily at the start of the trial. The dose will be increased by 7.5 mg weekly for subjects weighing less than 50 kg and up to 15 mg weekly for subjects weighing more than 50 kg depending upon efficacy and tolerability. | 20 |
| Placebo Subjects randomized to placebo arm will receive capsules identical in size and appearance to those subjects receiving study drug. Placebo capsules contain inactive ingredients.
Placebo: Subjects randomized to placebo will receive placebo for duration of the study | 10 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Mirtazapine | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 10.9 years STANDARD_DEVIATION 3.6 | 11.0 years STANDARD_DEVIATION 3.7 | 11.3 years STANDARD_DEVIATION 4.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 24 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 26 Participants | 9 Participants |
| Region of Enrollment United States | 20 participants | 30 participants | 10 participants |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Male | 17 Participants | 24 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 10 |
| other Total, other adverse events | 20 / 20 | 10 / 10 |
| serious Total, serious adverse events | 0 / 20 | 0 / 10 |
Outcome results
Primary
Mean 10-Week Change in Pediatric Anxiety Rating Scale 5-Item Total Score, Double-blind Phase
The Pediatric Anxiety Rating Scale (PARS) is a clinician-rated instrument that assesses anxiety symptoms that are commonly associated with social anxiety, separation anxiety, and generalized anxiety disorders. Scaled score ranges form 0-25 with higher scores indicating more severe anxiety symptoms. Means were estimated using a repeated measures linear regression model with treatment group, study week (in categories), and their interaction as covariates, and assuming a common mean between treatment groups at baseline. Confidence intervals reflect a Bonferroni multiple testing correction accounting for the selection of two primary outcomes.
Time frame: Weeks Baseline, 2, 4, 6, and 10
Population: All randomized study participants
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Mirtazapine | Mean 10-Week Change in Pediatric Anxiety Rating Scale 5-Item Total Score, Double-blind Phase | -4.9 score on a scale |
| Placebo | Mean 10-Week Change in Pediatric Anxiety Rating Scale 5-Item Total Score, Double-blind Phase | -3.2 score on a scale |
Primary
Proportion of Participants Who Responded to Treatment at 10 Weeks According to the Improvement Item of the Clinical Global Impression-Scale (Response Defined as CGI-I=1 or CGI-I=2)
The Clinical Global Impressions Global Improvement (CGI-I) is designed to take into account all factors to arrive at an assessment of response to treatment. The CGI-I scale ranges from 1 to 7 (1=very much improved; 2= much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse), with lower scores indicating improvement (1=very much improved and 2=much improved). In this study the CGI was focused on the target symptom of anxiety. Participants with a CGI-I score of 1 or 2 were classified as responders. The CGI-I was administered biweekly for 6 weeks and again at 10 weeks during the study. The participant who withdrew from the study before 10 weeks was not included in the calculations.
Time frame: Screen (Visit 1) Baseline (Visit 2) and Endpoint (Week 10)
Population: All randomized study participants with a 10 week CGI-I rating
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mirtazapine | Proportion of Participants Who Responded to Treatment at 10 Weeks According to the Improvement Item of the Clinical Global Impression-Scale (Response Defined as CGI-I=1 or CGI-I=2) | 0.47 Proportion of participants |
| Placebo | Proportion of Participants Who Responded to Treatment at 10 Weeks According to the Improvement Item of the Clinical Global Impression-Scale (Response Defined as CGI-I=1 or CGI-I=2) | 0.20 Proportion of participants |