Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders

• ClinicalTrials.gov Identifier: NCT01302964
• Recruitment Status: Completed
• First Posted: February 24, 2011
• Results First Posted: November 7, 2018
• Last Update Posted: November 7, 2018
• Sponsor: Massachusetts General Hospital
• Collaborator: Autism Speaks
• Information provided by (Responsible Party): Christopher John McDougle, M.D., Massachusetts General Hospital

Tracking Information

• First Submitted Date: August 25, 2010
• First Posted Date: February 24, 2011
• Results First Submitted Date: October 10, 2018
• Results First Posted Date: November 7, 2018
• Last Update Posted Date: November 7, 2018
• Study Start Date: August 2010
• Actual Primary Completion Date: October 10, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 10, 2018)

• Mean 10-Week Change in Pediatric Anxiety Rating Scale 5-Item Total Score, Double-blind Phase [ Time Frame: 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) [ Time Frame: 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.

Original Primary Outcome Measures (submitted: February 18, 2011)

• Pediatric Anxiety Rating Scale (PARS) [ Time Frame: Collected at screen (Visit 1) baseline (Visit 2) and endpoint (Week 10) ]
  Assesses severity across common anxiety disorders in children including generalized anxiety, social anxiety, separation anxiety and transition-associated anxiety.
• Clinical Global Impressions (CGI) [ Time Frame: Screen (Visit 1) Baseline (Visit 2) and Endpoint (Week 10) ]
  The CGI is designed to take into account all factors to arrive at an assessment of severity and response to treatment.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Autism Spectrum Disorders

Intervention

• Drug: Placebo
  Subjects randomized to placebo will receive placebo for duration of the study
  Other Name: Sugar pill
• Drug: Mirtazapine
  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.
  Other Name: Remeron

Study Arms

• Experimental: Mirtazapine
  The starting dose for subjects is 7.5 mg daily. The maximum daily dose will be 45 mg.
  Intervention: Drug: Mirtazapine
• Placebo Comparator: 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.
  Intervention: Drug: Placebo

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 18, 2011): 30
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: October 10, 2017
• Actual Primary Completion Date: October 10, 2017 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 5 Years to 17 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01302964
• Other Study ID Numbers: 2012P001009
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Christopher John McDougle, M.D., Massachusetts General Hospital
• Original Responsible Party: Christopher J. McDougle, M.D., Indiana University School of Medicine/ Department of Psychiatry
• Current Study Sponsor: Massachusetts General Hospital
• Original Study Sponsor: Indiana University
• Collaborators: Autism Speaks

Investigators

• Principal Investigator: Christopher J. McDougle, M.D.; Indiana University School of Medicine

• PRS Account: Massachusetts General Hospital
• Verification Date: October 2018