Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
Primary Purpose
Autism Spectrum Disorders
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Placebo
Mirtazapine
Sponsored by
About this trial
This is an interventional treatment trial for Autism Spectrum Disorders focused on measuring Autistic Disorder, Asperger's Disorder, Pervasive Developmental Disorder
Eligibility Criteria
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
Sites / Locations
- Riley Child and Adolescent Psychiatry Clinic Riley Hospital
- Lurie Center -MassGeneral Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Mirtazapine
Placebo
Arm Description
The starting dose for subjects is 7.5 mg daily. The maximum daily dose will be 45 mg.
Subjects randomized to placebo arm will receive capsules identical in size and appearance to those subjects receiving study drug. Placebo capsules contain inactive ingredients.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT01302964
First Posted
August 25, 2010
Last Updated
October 10, 2018
Sponsor
Massachusetts General Hospital
Collaborators
Autism Speaks
1. Study Identification
Unique Protocol Identification Number
NCT01302964
Brief Title
Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
Official Title
Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
August 2010 (undefined)
Primary Completion Date
October 10, 2017 (Actual)
Study Completion Date
October 10, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
Autism Speaks
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autism Spectrum Disorders
Keywords
Autistic Disorder, Asperger's Disorder, Pervasive Developmental Disorder
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Mirtazapine
Arm Type
Experimental
Arm Description
The starting dose for subjects is 7.5 mg daily. The maximum daily dose will be 45 mg.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects randomized to placebo arm will receive capsules identical in size and appearance to those subjects receiving study drug. Placebo capsules contain inactive ingredients.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Sugar pill
Intervention Description
Subjects randomized to placebo will receive placebo for duration of the study
Intervention Type
Drug
Intervention Name(s)
Mirtazapine
Other Intervention Name(s)
Remeron
Intervention Description
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.
Primary Outcome Measure Information:
Title
Mean 10-Week Change in Pediatric Anxiety Rating Scale 5-Item Total Score, Double-blind Phase
Description
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
Title
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)
Description
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christopher J. McDougle, M.D.
Organizational Affiliation
Indiana University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Riley Child and Adolescent Psychiatry Clinic Riley Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Lurie Center -MassGeneral Hospital
City
Lexington
State/Province
Massachusetts
ZIP/Postal Code
02421
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
35241779
Citation
McDougle CJ, Thom RP, Ravichandran CT, Palumbo ML, Politte LC, Mullett JE, Keary CJ, Erickson CA, Stigler KA, Mathieu-Frasier L, Posey DJ. A randomized double-blind, placebo-controlled pilot trial of mirtazapine for anxiety in children and adolescents with autism spectrum disorder. Neuropsychopharmacology. 2022 May;47(6):1263-1270. doi: 10.1038/s41386-022-01295-4. Epub 2022 Mar 3.
Results Reference
derived
Links:
URL
http://www.massgeneral.org/children/services/lurie-center/research.aspx
Description
Lurie Center Research
Learn more about this trial
Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
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