Trial Outcomes & Findings for Oxytocin on Irritability/Emotional Dysregulation of Disruptive Behavior and Mood Disorders (NCT NCT02824627)
NCT ID: NCT02824627
Last Updated: 2023-10-05
Results Overview
The Affective Reactivity Index-Youth (ARI-Y) is a 7 item inventory (youth self-report) specifically designed to measure irritability and emotional dysregulation as a dimensional construct across psychopathologies in children and adolescents (Stringaris et al., 2012). ARI scores range from 0 to 12. Total scores are reported. Higher scores are indicative of more (worse) irritability. We report the change in ARI-Y score as our outcome measure.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
58 participants
Primary outcome timeframe
baseline and 21 days
Results posted on
2023-10-05
Participant Flow
Participant milestones
| Measure |
Oxytocin
Subjects weighing \>40kg will receive a total of 24 IU of oxytocin delivered as 2- 6 IU puffs to each nostril once daily. Subjects weighing \< 40kg will receive a total of 12 IU of oxytocin delivered as 1- 6 IU puff to each nostril daily. Subjects will receive 14 to 21 days of daily oxytocin administration.
Oxytocin: A growing body of data shows that intra-nasal administration of oxytocin has promise for treating a host of psychiatric disorders. Considerable data indicates that oxytocin reduces amygdala response to negative stimuli in patients with generalized anxiety disorder, borderline personality disorder, and post-traumatic stress disorder. Given that one of the potential underlying neurobiological mechanisms of irritability and emotional dysregulation in pediatric population with disruptive behavior and mood disorder is the hyperactivity of amygdala to negative emotional stimuli, and that oxytocin reduces this, it is critical to determine the extent to which this intervention improves irritability and emotional dysregulation in children and adolescents with disruptive behavior and mood disorders.
|
Placebo
Subjects weighing\>40kg will 2 puffs of placebo to each nostril daily. Subjects weighing \<40kg will receive 1 puff per day. Subjects will receive 14-21 days of placebo administration.
Placebo: Inactive substance administered in volume equivalent to volume administered in active treatment arm.
|
|---|---|---|
|
Overall Study
STARTED
|
28
|
30
|
|
Overall Study
COMPLETED
|
25
|
27
|
|
Overall Study
NOT COMPLETED
|
3
|
3
|
Reasons for withdrawal
| Measure |
Oxytocin
Subjects weighing \>40kg will receive a total of 24 IU of oxytocin delivered as 2- 6 IU puffs to each nostril once daily. Subjects weighing \< 40kg will receive a total of 12 IU of oxytocin delivered as 1- 6 IU puff to each nostril daily. Subjects will receive 14 to 21 days of daily oxytocin administration.
Oxytocin: A growing body of data shows that intra-nasal administration of oxytocin has promise for treating a host of psychiatric disorders. Considerable data indicates that oxytocin reduces amygdala response to negative stimuli in patients with generalized anxiety disorder, borderline personality disorder, and post-traumatic stress disorder. Given that one of the potential underlying neurobiological mechanisms of irritability and emotional dysregulation in pediatric population with disruptive behavior and mood disorder is the hyperactivity of amygdala to negative emotional stimuli, and that oxytocin reduces this, it is critical to determine the extent to which this intervention improves irritability and emotional dysregulation in children and adolescents with disruptive behavior and mood disorders.
|
Placebo
Subjects weighing\>40kg will 2 puffs of placebo to each nostril daily. Subjects weighing \<40kg will receive 1 puff per day. Subjects will receive 14-21 days of placebo administration.
Placebo: Inactive substance administered in volume equivalent to volume administered in active treatment arm.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
2
|
|
Overall Study
Lost to Follow-up
|
2
|
1
|
Baseline Characteristics
Oxytocin on Irritability/Emotional Dysregulation of Disruptive Behavior and Mood Disorders
Baseline characteristics by cohort
| Measure |
Oxytocin
n=25 Participants
Subjects weighing \>40kg will receive a total of 24 IU of oxytocin delivered as 2- 6 IU puffs to each nostril once daily. Subjects weighing \< 40kg will receive a total of 12 IU of oxytocin delivered as 1- 6 IU puff to each nostril daily. Subjects will receive 14 to 21 days of daily oxytocin administration.
Oxytocin: A growing body of data shows that intra-nasal administration of oxytocin has promise for treating a host of psychiatric disorders. Considerable data indicates that oxytocin reduces amygdala response to negative stimuli in patients with generalized anxiety disorder, borderline personality disorder, and post-traumatic stress disorder. Given that one of the potential underlying neurobiological mechanisms of irritability and emotional dysregulation in pediatric population with disruptive behavior and mood disorder is the hyperactivity of amygdala to negative emotional stimuli, and that oxytocin reduces this, it is critical to determine the extent to which this intervention improves irritability and emotional dysregulation in children and adolescents with disruptive behavior and mood disorders.
|
Placebo
n=27 Participants
Subjects weighing\>40kg will 2 puffs of placebo to each nostril daily. Subjects weighing \<40kg will receive 1 puff per day. Subjects will receive 14-21 days of placebo administration.
Placebo: Inactive substance administered in volume equivalent to volume administered in active treatment arm.
|
Total
n=52 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
14.5 years
STANDARD_DEVIATION 2.2 • n=5 Participants
|
13.8 years
STANDARD_DEVIATION 1.9 • n=7 Participants
|
13.9 years
STANDARD_DEVIATION 2.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
20 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Affective Reactivity Index-Youth
|
6.6 units on a scale
STANDARD_DEVIATION 2.2 • n=5 Participants
|
6.5 units on a scale
STANDARD_DEVIATION 2.7 • n=7 Participants
|
6.6 units on a scale
STANDARD_DEVIATION 2.4 • n=5 Participants
|
|
Affective Reactivity Index- Parent
|
7.5 units on a scale
STANDARD_DEVIATION 2.7 • n=5 Participants
|
8.7 units on a scale
STANDARD_DEVIATION 2.0 • n=7 Participants
|
8.1 units on a scale
STANDARD_DEVIATION 2.4 • n=5 Participants
|
|
Clinical Global Impression- Severity
|
4.4 units on a scale
STANDARD_DEVIATION 0.6 • n=5 Participants
|
4.6 units on a scale
STANDARD_DEVIATION 0.7 • n=7 Participants
|
4.5 units on a scale
STANDARD_DEVIATION 0.6 • n=5 Participants
|
PRIMARY outcome
Timeframe: baseline and 21 daysThe Affective Reactivity Index-Youth (ARI-Y) is a 7 item inventory (youth self-report) specifically designed to measure irritability and emotional dysregulation as a dimensional construct across psychopathologies in children and adolescents (Stringaris et al., 2012). ARI scores range from 0 to 12. Total scores are reported. Higher scores are indicative of more (worse) irritability. We report the change in ARI-Y score as our outcome measure.
Outcome measures
| Measure |
Oxytocin
n=25 Participants
Subjects weighing \>40kg will receive a total of 24 IU of oxytocin delivered as 2- 6 IU puffs to each nostril once daily. Subjects weighing \< 40kg will receive a total of 12 IU of oxytocin delivered as 1- 6 IU puff to each nostril daily. Subjects will receive 14 to 21 days of daily oxytocin administration.
Oxytocin: A growing body of data shows that intra-nasal administration of oxytocin has promise for treating a host of psychiatric disorders. Considerable data indicates that oxytocin reduces amygdala response to negative stimuli in patients with generalized anxiety disorder, borderline personality disorder, and post-traumatic stress disorder. Given that one of the potential underlying neurobiological mechanisms of irritability and emotional dysregulation in pediatric population with disruptive behavior and mood disorder is the hyperactivity of amygdala to negative emotional stimuli, and that oxytocin reduces this, it is critical to determine the extent to which this intervention improves irritability and emotional dysregulation in children and adolescents with disruptive behavior and mood disorders.
|
Placebo
n=27 Participants
Subjects weighing\>40kg will 2 puffs of placebo to each nostril daily. Subjects weighing \<40kg will receive 1 puff per day. Subjects will receive 14-21 days of placebo administration.
Placebo: Inactive substance administered in volume equivalent to volume administered in active treatment arm.
|
|---|---|---|
|
Change in Affective Reactivity Index - Youth (ARI-Y)
|
-2.9 score on a scale
Standard Deviation 2.3
|
-0.8 score on a scale
Standard Deviation 2.5
|
PRIMARY outcome
Timeframe: 21 days (study endpoint)The Clinical Global Impression: Severity scale is a single-item clinician rated measure of the clinician's impression of the degree of illness of the subject in terms of level of irritability from study start to endpoint. Ratings are 1=normal, not ill, 2= borderline ill, 3= minimally ill, 4= moderately ill, 5= markedly ill, 6= severely ill; 7= very severely ill. A single score of 1 to 7 is given at study endpoint for each subject. A higher score indicates worsening of the subject's irritability based on clinician impression.
Outcome measures
| Measure |
Oxytocin
n=25 Participants
Subjects weighing \>40kg will receive a total of 24 IU of oxytocin delivered as 2- 6 IU puffs to each nostril once daily. Subjects weighing \< 40kg will receive a total of 12 IU of oxytocin delivered as 1- 6 IU puff to each nostril daily. Subjects will receive 14 to 21 days of daily oxytocin administration.
Oxytocin: A growing body of data shows that intra-nasal administration of oxytocin has promise for treating a host of psychiatric disorders. Considerable data indicates that oxytocin reduces amygdala response to negative stimuli in patients with generalized anxiety disorder, borderline personality disorder, and post-traumatic stress disorder. Given that one of the potential underlying neurobiological mechanisms of irritability and emotional dysregulation in pediatric population with disruptive behavior and mood disorder is the hyperactivity of amygdala to negative emotional stimuli, and that oxytocin reduces this, it is critical to determine the extent to which this intervention improves irritability and emotional dysregulation in children and adolescents with disruptive behavior and mood disorders.
|
Placebo
n=27 Participants
Subjects weighing\>40kg will 2 puffs of placebo to each nostril daily. Subjects weighing \<40kg will receive 1 puff per day. Subjects will receive 14-21 days of placebo administration.
Placebo: Inactive substance administered in volume equivalent to volume administered in active treatment arm.
|
|---|---|---|
|
Clinical Global Impression: Severity
|
2.72 score on a scale
Standard Deviation 0.79
|
3.33 score on a scale
Standard Deviation 1.07
|
SECONDARY outcome
Timeframe: baseline and 21 daysPopulation: Number of participants who completed 2 scans (baseline and at the end of the study).
percent change in BOLD response from baseline to study end point
Outcome measures
| Measure |
Oxytocin
n=22 Participants
Subjects weighing \>40kg will receive a total of 24 IU of oxytocin delivered as 2- 6 IU puffs to each nostril once daily. Subjects weighing \< 40kg will receive a total of 12 IU of oxytocin delivered as 1- 6 IU puff to each nostril daily. Subjects will receive 14 to 21 days of daily oxytocin administration.
Oxytocin: A growing body of data shows that intra-nasal administration of oxytocin has promise for treating a host of psychiatric disorders. Considerable data indicates that oxytocin reduces amygdala response to negative stimuli in patients with generalized anxiety disorder, borderline personality disorder, and post-traumatic stress disorder. Given that one of the potential underlying neurobiological mechanisms of irritability and emotional dysregulation in pediatric population with disruptive behavior and mood disorder is the hyperactivity of amygdala to negative emotional stimuli, and that oxytocin reduces this, it is critical to determine the extent to which this intervention improves irritability and emotional dysregulation in children and adolescents with disruptive behavior and mood disorders.
|
Placebo
n=21 Participants
Subjects weighing\>40kg will 2 puffs of placebo to each nostril daily. Subjects weighing \<40kg will receive 1 puff per day. Subjects will receive 14-21 days of placebo administration.
Placebo: Inactive substance administered in volume equivalent to volume administered in active treatment arm.
|
|---|---|---|
|
Functional MRI (fMRI) BOLD Response Changes
|
-0.045 mean percent change
Standard Deviation 0.007
|
0.045 mean percent change
Standard Deviation 0.009
|
Adverse Events
Oxytocin
Serious events: 0 serious events
Other events: 21 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 25 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Oxytocin
n=25 participants at risk
Subjects weighing \>40kg will receive a total of 24 IU of oxytocin delivered as 2- 6 IU puffs to each nostril once daily. Subjects weighing \< 40kg will receive a total of 12 IU of oxytocin delivered as 1- 6 IU puff to each nostril daily. Subjects will receive 14 to 21 days of daily oxytocin administration.
Oxytocin: A growing body of data shows that intra-nasal administration of oxytocin has promise for treating a host of psychiatric disorders. Considerable data indicates that oxytocin reduces amygdala response to negative stimuli in patients with generalized anxiety disorder, borderline personality disorder, and post-traumatic stress disorder. Given that one of the potential underlying neurobiological mechanisms of irritability and emotional dysregulation in pediatric population with disruptive behavior and mood disorder is the hyperactivity of amygdala to negative emotional stimuli, and that oxytocin reduces this, it is critical to determine the extent to which this intervention improves irritability and emotional dysregulation in children and adolescents with disruptive behavior and mood disorders.
|
Placebo
n=27 participants at risk
Subjects weighing\>40kg will 2 puffs of placebo to each nostril daily. Subjects weighing \<40kg will receive 1 puff per day. Subjects will receive 14-21 days of placebo administration.
Placebo: Inactive substance administered in volume equivalent to volume administered in active treatment arm.
|
|---|---|---|
|
General disorders
Drowsiness
|
36.0%
9/25 • Number of events 9 • 21 days
|
22.2%
6/27 • Number of events 6 • 21 days
|
|
Nervous system disorders
Headache
|
12.0%
3/25 • Number of events 3 • 21 days
|
29.6%
8/27 • Number of events 8 • 21 days
|
|
Psychiatric disorders
Sleep Disturbance
|
8.0%
2/25 • Number of events 2 • 21 days
|
0.00%
0/27 • 21 days
|
|
Nervous system disorders
Dizziness
|
4.0%
1/25 • Number of events 1 • 21 days
|
3.7%
1/27 • Number of events 1 • 21 days
|
|
Psychiatric disorders
Mood Changes
|
12.0%
3/25 • Number of events 3 • 21 days
|
29.6%
8/27 • Number of events 8 • 21 days
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/25 • 21 days
|
7.4%
2/27 • Number of events 2 • 21 days
|
|
Infections and infestations
Upper respiratory infection
|
0.00%
0/25 • 21 days
|
7.4%
2/27 • Number of events 2 • 21 days
|
|
Blood and lymphatic system disorders
Nose bleeding
|
8.0%
2/25 • Number of events 2 • 21 days
|
3.7%
1/27 • Number of events 1 • 21 days
|
|
Gastrointestinal disorders
Bad taste
|
4.0%
1/25 • Number of events 1 • 21 days
|
0.00%
0/27 • 21 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place