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

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ClinicalTrials.gov Identifier: NCT01302964

Recruitment Status : Completed

First Posted : February 24, 2011

Results First Posted : November 7, 2018

Last Update Posted : November 7, 2018

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

Autism Speaks

Information provided by (Responsible Party):

Christopher John McDougle, M.D., Massachusetts General Hospital

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition	Autism Spectrum Disorders
Interventions	Drug: Placebo Drug: Mirtazapine
Enrollment	30

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Mirtazapine	Placebo
Arm/Group Description	The starting dose for subjects is 7...	Subjects randomized to placebo arm ...
Arm/Group Description	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.	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
Period Title: Overall Study
Started	20	10
Completed	19	10
Not Completed	1	0
Reason Not Completed
Adverse Event	1	0

Baseline Characteristics

Arm/Group Title		Mirtazapine	Placebo	Total
Arm/Group Description		The starting dose for subjects is 7...	Subjects randomized to placebo arm ...	Total of all reporting groups
Arm/Group Description		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.	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	Total of all reporting groups
Overall Number of Baseline Participants		20	10	30
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	20 participants	10 participants	30 participants
		10.9 (3.6)	11.3 (4.1)	11.0 (3.7)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	20 participants	10 participants	30 participants
	Female	3 15.0%	3 30.0%	6 20.0%
	Male	17 85.0%	7 70.0%	24 80.0%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	20 participants	10 participants	30 participants
	Hispanic or Latino	2 10.0%	2 20.0%	4 13.3%
	Not Hispanic or Latino	16 80.0%	8 80.0%	24 80.0%
	Unknown or Not Reported	2 10.0%	0 0.0%	2 6.7%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	20 participants	10 participants	30 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	1 5.0%	0 0.0%	1 3.3%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	1 5.0%	1 10.0%	2 6.7%
	White	17 85.0%	9 90.0%	26 86.7%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	1 5.0%	0 0.0%	1 3.3%
Region of Enrollment Measure Type: Number Unit of measure: Participants
United States	Number Analyzed	20 participants	10 participants	30 participants
United States		20	10	30

Outcome Measures

1.Primary Outcome


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 instrum...
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

Outcome Measure Data

Analysis Population Description

All randomized study participants


Arm/Group Title	Mirtazapine	Placebo
Arm/Group Description:	The starting dose for subjects is 7...	Subjects randomized to placebo arm ...
Arm/Group Description:	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 subject weighing less than 50kg and up to 15 mg weekly for subjects weighing more than 50kg depending upon efficacy and tolerability.	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
Overall Number of Participants Analyzed	20	10
Mean (95% Confidence Interval) Unit of Measure: score on a scale
	-4.9 (-7.3 to -2.6)	-3.2 (-6.5 to 0.2)

2.Primary Outcome


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...
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)

Outcome Measure Data

Analysis Population Description

All randomized study participants with a 10 week CGI-I rating


Arm/Group Title	Mirtazapine	Placebo
Arm/Group Description:	The starting dose for subjects is 7...	Subjects randomized to placebo arm ...
Arm/Group Description:	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 subject weighing less than 50kg and up to 15 mg weekly for subjects weighing more than 50kg depending upon efficacy and tolerability.	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
Overall Number of Participants Analyzed	19	10
Measure Type: Number Unit of Measure: Proportion of participants
	0.47	0.20

Adverse Events

Time Frame	Ten weeks or at the time of latest data collection for the participant who did not complete the study.
Adverse Event Reporting Description	Adverse event information was collected via a structured side effect rating scale completed with the participant and their primary caregiver. This included a list of side-effects that have been reported with mirtazapine at a rate greater than 1%. The physician also asked about any visits to the doctor, new medication use, or any other complaints. Events that were not present at baseline and occurred or worsened after the date of randomization are reported.

Arm/Group Title	Mirtazapine	Placebo
Arm/Group Description	The starting dose for subjects is 7...	Subjects randomized to placebo arm ...
Arm/Group Description	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 subject weighing less than 50kg and up to 15 mg weekly for subjects weighing more than 50kg depending upon efficacy and tolerability.	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
All-Cause Mortality
	Mirtazapine	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/20 (0.00%)	0/10 (0.00%)
Serious Adverse Events Serious Adverse Events
	Mirtazapine	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/20 (0.00%)	0/10 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Mirtazapine	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	20/20 (100.00%)	10/10 (100.00%)
Eye disorders
Eye Irritation ^†	1/20 (5.00%)	0/10 (0.00%)
Gastrointestinal disorders
Nausea ^†	6/20 (30.00%)	3/10 (30.00%)
Diarrhea ^†	5/20 (25.00%)	2/10 (20.00%)
Stomach or abdominal discomfort ^†	5/20 (25.00%)	4/10 (40.00%)
Vomiting ^†	3/20 (15.00%)	4/10 (40.00%)
Constipation ^†	3/20 (15.00%)	3/10 (30.00%)
Taste abnormality ^†	1/20 (5.00%)	0/10 (0.00%)
Indigestion ^†	0/20 (0.00%)	1/10 (10.00%)
General disorders
Sedation/Drowsiness ^†	12/20 (60.00%)	6/10 (60.00%)
Appetite increase ^†	10/20 (50.00%)	2/10 (20.00%)
Appetite decrease ^†	2/20 (10.00%)	2/10 (20.00%)
Fever ^†	2/20 (10.00%)	2/10 (20.00%)
Dry mouth ^†	2/20 (10.00%)	0/10 (0.00%)
Tiredness/fatigue ^†	2/20 (10.00%)	0/10 (0.00%)
Accidental injury ^†	1/20 (5.00%)	0/10 (0.00%)
Other Pain ^†	1/20 (5.00%)	0/10 (0.00%)
Immune system disorders
Allergies Not Otherwise Specified ^†	1/20 (5.00%)	1/10 (10.00%)
Infections and infestations
Nasal congestion or Cold ^†	4/20 (20.00%)	2/10 (20.00%)
Unspecified or not otherwise listed nose/throat ^†	2/20 (10.00%)	1/10 (10.00%)
Sinus condition ^†	2/20 (10.00%)	0/10 (0.00%)
Flu or upper respiratory problems ^†	0/20 (0.00%)	2/10 (20.00%)
Ear Infection ^†	1/20 (5.00%)	0/10 (0.00%)
Sore throat ^†	1/20 (5.00%)	0/10 (0.00%)
Throat infection ^†	1/20 (5.00%)	0/10 (0.00%)
Unspecified or not otherwise listed mouth ^†	0/20 (0.00%)	1/10 (10.00%)
Musculoskeletal and connective tissue disorders
Unspecified or not otherwise listed, musculoskeletal ^†	1/20 (5.00%)	0/10 (0.00%)
Nervous system disorders
Headache ^†	3/20 (15.00%)	2/10 (20.00%)
Sensory sensitivity ^†	1/20 (5.00%)	0/10 (0.00%)
Psychiatric disorders
Aggression ^† [1]	5/20 (25.00%)	4/10 (40.00%)
Nightmares or Dreams ^†	4/20 (20.00%)	2/10 (20.00%)
Irritability ^†	7/20 (35.00%)	3/10 (30.00%)
Sadness ^†	4/20 (20.00%)	3/10 (30.00%)
Difficulty falling asleep ^†	3/20 (15.00%)	1/10 (10.00%)
Interrupted sleep/other sleep problems ^†	2/20 (10.00%)	0/10 (0.00%)
Concentration difficulty ^†	2/20 (10.00%)	1/10 (10.00%)
Anxiety/Nervousness/Worry ^†	2/20 (10.00%)	0/10 (0.00%)
Body-focused repetitive behavior ^†	2/20 (10.00%)	0/10 (0.00%)
Change in speech ^†	2/20 (10.00%)	0/10 (0.00%)
Euphoria/Giddiness ^†	1/20 (5.00%)	0/10 (0.00%)
Increased motor activity ^†	1/20 (5.00%)	0/10 (0.00%)
Restlessness/Agitation including fidgety ^†	1/20 (5.00%)	1/10 (10.00%)
Unspecified or not otherwise listed psych ^†	1/20 (5.00%)	0/10 (0.00%)
Decreased motor activity ^†	1/20 (5.00%)	0/10 (0.00%)
Suicidal ideas ^†	1/20 (5.00%)	0/10 (0.00%)
Social withdrawal ^†	2/20 (10.00%)	2/10 (20.00%)
Stereotypy ^†	1/20 (5.00%)	1/10 (10.00%)
Compulsions ^†	1/20 (5.00%)	0/10 (0.00%)
Disinhibition ^†	1/20 (5.00%)	0/10 (0.00%)
Emotional outburst ^†	1/20 (5.00%)	0/10 (0.00%)
Self-injurious behavior ^†	2/20 (10.00%)	0/10 (0.00%)
Renal and urinary disorders
Enuresis ^†	3/20 (15.00%)	1/10 (10.00%)
Skin and subcutaneous tissue disorders
Localized rash ^†	2/20 (10.00%)	1/10 (10.00%)
Hair problems ^†	1/20 (5.00%)	0/10 (0.00%)
Sweating ^†	1/20 (5.00%)	0/10 (0.00%)
Vascular disorders
Dizziness/faintness ^†	2/20 (10.00%)	1/10 (10.00%)
Intermittent nosebleed ^†	1/20 (5.00%)	0/10 (0.00%)
† Indicates events were collected by systematic assessment [1] Aggression (e.g. verbal threats to harm others, physical aggressions, not including disobedience or defiant/oppositional behavior)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Christopher J. McDougle, MD
Organization:	Massachusetts General Hospital
Phone:	781-860-1783
EMail:	cmcdougle@mgh.harvard.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Layout table for additonal information

Responsible Party:	Christopher John McDougle, M.D., Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT01302964
Other Study ID Numbers:	2012P001009
First Submitted:	August 25, 2010
First Posted:	February 24, 2011
Results First Submitted:	October 10, 2018
Results First Posted:	November 7, 2018
Last Update Posted:	November 7, 2018

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