Autism Spectrum Disorders
Conditions
Keywords
autism, ASD, autistic, Asperger's, PDD-NOS, oxytocin
Brief summary
The purpose of this research study is to learn about the effects of supplemental intranasal oxytocin as a treatment for improving social difficulties in children and adolescents with autism. This study will also provide additional information about the safety and tolerability of intranasal oxytocin. Investigators expect oxytocin will increase social motivation, improving daily living skills and quality of life.
Detailed description
There is a tremendous unmet need for accessible treatments that address core symptoms of ASD and are safe for sustained use. The Study of Oxytocin in ASD to improve Reciprocal Social Behaviors or (SOARS-B) will test a very promising potential treatment-intranasal oxytocin-for ASD's fundamental social communication deficits in a large, group of verbal and nonverbal children. SOARS-B will also provide information about the regulation of DNA methylation and transcription of the oxytocin receptor gene (OXTR), as well as other genes relevant to oxytocin's CNS activity, as a function of time and in response to oxytocin treatment. These data will fill a key gap in our understanding of oxytocin's role in ASD and its ability to alter epigenetic modifications of the OXTR.
Interventions
DRUGDouble blind phase Placebo Nasal Spray
This nasal spray will contain all of the ingredients that are in the active oxytocin spray in the same quantities, except oxytocin will NOT be added to the solution. It will be packaged using the same container system as the active oxytocin nasal spray. Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. Dose titration will occur using exactly the same criteria and procedures as for active study drug.
DRUGdouble Blind Oxytocin Nasal Spray
Each insufflation will deliver 8 IU or 24 IU of oxytocin. A maximum of 3 insufflations at a time will be required. Dosing will be flexible between 8 IU/day and 80 IU/day, typically in two divided doses delivered in the morning and in the afternoon. Doses will typically increase by 8 IU twice daily (BID) at week 2 and weeks 4 and 8 until achieving the target dose of 24 IU BID at week 8. Subsequently doses may be increased in 8 IU BID increments ONLY at each visit until a maximum dose of 40 IU BID is achieved.Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. During the open label phase after approximately March 2019 the study used only the 24 IU /0.10 ml formulation and the maximum dose was 72 IU per day.
DRUGOpen Label intranasal oxytocin
All participants who completed the 24 week double blind phase were eligible to join a 24 week open label phase in which all participants received intranasal oxytocin
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Linmarie Sikich
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Quadruple
Intervention model description
Randomized, Double-blind, placebo-controlled clinical trial for 24 weeks. Followed by 24 week open label treatment period in which ALL participants receive Oxytocin
Eligibility
Sex/Gender
ALL
Age
3 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Be between the ages of 3 years 0 months and 17 years 11 months at the time of randomization * Be diagnosed by clinician experienced in assessment of ASD with autistic disorder, Asperger's syndrome, or PDD-NOS using DSM-V-TR criteria * Must have clinical diagnosis of ASD confirmed using the Autism Diagnostic Observation Scale (ADOS, Lord et al., 2001) * Must have clinical diagnosis of ASD confirmed using the Autism Diagnostic Interview-Revised (ADI-R, Rutter, 2003). ASD criteria proposed by Risi (2006). Specifically, subject must be within 1 point of autism criteria on both social and communication domains of the ADI or meet autism criteria in one of these ADI domains and come within 2 points of autism criteria in the other * Have a guardian who is able to provide informed consent * If cognitively able, subject must be able to provide informed assent/consent
Exclusion criteria
* Have a known diagnosis of Rett Syndrome or Childhood Disintegrative Disorder, or have marked sensory impairment such as deafness or blindness * Have active cardiovascular disease or renal disease that is not controlled by medication * Subjects who are pregnant, lactating, or who refuse to practice contraception if sexually active * Subjects who have had changes in allied health therapies, behavioral or educational interventions within the two months prior to randomization other than those associated with school holidays * Subjects who have had changes in psychiatric medications within 4 weeks of randomization * Subjects who have had previous chronic treatment with oxytocin * Subjects who have caretakers who are unable to speak English, be consistently present at visits to report on symptoms, or are otherwise judged as unable to comply with the protocol by the data collection site team * Subjects with active seizures within the 6 months preceding screening or baseline -added part way through study in response to subject death.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity | Least Mean Squares Double-blind phase: change from baseline to week 24 | The primary outcome is Change in Aberrant Behavior Checklist-Modified Social Withdrawal subscale- a measure of reciprocal social behaviors. ABC-mSW is a modification of the ABC-Lethargy subscale. The ABC-mSW consists of the sum of questions 5,12,16, 20, 23, 26, 30, 37, 40, 42, 43, 55, and 58. In contrast to the ABC-Lethargy subscale it eliminates question 3 (listless, sluggish, inactive), question 32 (sits or stands in one position for a long time), and question 53 (inactive, never moves spontaneously). Thirteen individual items are scored 0-3, therefore the range is 0-39. Higher score indicates lower social reciprocity. Repeated measures were obtained at baseline, weeks 4, 8, 12, 16, 20, 24. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Sociability Factor (SF) | Double-blind phase: change in least means squares between week 0 & 24. | The Sociability Factor (SF) is a summed measure of the13 items of the ABC-SW and the 18 items of the Pervasive Development Disorders Behavior Inventory-Screening Version (PDDBI-SV).The PDDBI-SV assesses both adaptive social behaviors and social problems typical of ASD. The adaptive behaviors are reverse scored so that all the analyzed scores range from 0-performing in a neurotypical fashion to 3 typically performs in a way associated with ASD. the total # of items on this summed measure is 31 with a range from 0 to 93. More impaired social functioning indicated by higher scores. This measure was changed to a secondary outcome in the final statistical analysis plan. |
| Change in Social Responsiveness Scale-2 (SRS-2) Social Motivation Subscale Score | Double-blind phase: baseline, weeks 12, 24 | The SRS-Social Motivation subscale was developed to provide a quantitative measure of social impairments typically observed in ASD in children 3-18 years. Reported as T-score with a range of 38-90 for both boys and girls. Higher score indicates more severe clinical condition. Lower value in change indicates more improvement. |
| Change in Stanford Binet-5th Edition (SB-5) IQ Score | Double-blind phase: baseline to week 24 | Cognitive skills will be assessed using the Stanford Binet-5th Edition (SB-5) (Roid). Acceptable IQ range is 47-153, with higher score being better. Higher change scores indicate more improvement. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Caregiver Strain Questionnaire (CSQ) Subjective Internalizing Subscale Score | Double-blind phase: baseline, week 24 | Caregiver questionnaire that assesses the impact of caring for the proband on caregiver and family. CSQ subscale scores are ranged from 1 to 5. with each item of the subscale having the same range, the sum of the items within the subscale are summed, and the mean score is determined (I.e. a single # between 1 and 5) and reported. Higher scores indicate more caregiver strain. Lower value in change indicates more improvement. |
| Change in Vineland II Adaptive Behavior Scales (VABS-II) Socialization Domain Score | Double-blind phase: baseline, week 24; Open Label: week 48 | Functional skills will be assessed using the VABS-II Socialization Domain Score. Uses standard score with a mean of 100 and SD of 15 with a range of 20-160. Higher score is better. Higher value in change indicates more improvement. |
| Change in Caregiver Strain Questionnaire (CSQ) Objective Subscale Score | Double-blind phase: baseline, week 24; Open Label: week 48 | Caregiver questionnaire that assesses the impact of caring for the proband on caregiver and family. CSQ subscale scores are ranged from 1 to 5. Higher score indicates more caregiver strain. Lower value in change indicates more improvement. The analysis directions for the instrument that are used in these analyses are the mean of all the responses in the scale or subscale. |
| Social Responsiveness Scale-2 (SRS-2) Social Motivation Subscale Score | Open Label: weeks 24, 48 | The SRS-Social Motivation subscale was developed to provide a quantitative measure of social impairments typically observed in ASD in children 3-18 years. Reported as T-score with a range of 38-90 for both boys and girls. Higher score indicates more severe clinical condition. Lower value in change indicates more improvement. |
| Change in Vineland II Adaptive Behavior Scales (VABS-II) Composite Score | Double-blind phase: baseline, week 24 | Functional skills including communication will be assessed using the VABS-II Adaptive Behavior Composite Score. Uses standard score with a mean of 100 and SD of 15 with a range of 20-160. Higher score is better. Higher value in change indicates more improvement. |
| Change in Clinical Global Impressions -Improvement Score (CGI-I) | Double blind phase: change from Baseline to week 12, and week 24. Open label phase change from week 24 to week 48 | The Clinical Global Impressions - Improvement score and Severity score, which is routinely used in pharmacologic clinical trials, will capture the study physician's global impression of response. scores of 1 and 2 are considered as a percentage of total subjects in arm |
| Reading Mind in the Eyes Test is an Objective Measures of the Extent to Which Verbal Participants With Rudimentary Knowledge of Emotion Names Are Able to Correctly Identify the Emotion Shown in a Black and White Picture of the Eyes and Nose of an Actor. | Double blind phase: change from Baseline and week 24. Note: only those who demonstrated understanding of these concepts were included in sample. | This computerized task consists of a series of pictures of eyes in which the participant needs to determine which emotion the eyes are expressing from 4 emotions listed along with the picture. The outcome is the % of pictures with correct emotion identified. The range is 0 to 100%. The larger percent identified correctly indicates better ability to perceive emotions. An increase or positive change indicates better ability to identify emotions since baseline. |
| Change in Caregiver Strain Questionnaire (CSQ) Subjective Externalizing Subscale Score | Double-blind phase: baseline, week 24; Open Label: week 48 | Caregiver questionnaire that assesses the impact of caring for the proband on caregiver and family. CSQ subscale scores are ranged from 1 to 5. Higher score indicates more caregiver strain. Lower value in change indicates more improvement. |
| Change in Vineland II Adaptive Behavior Scales (VABS-II) Daily Living Domain Score | Double-blind phase: baseline, week 24; Open Label: week 48 | Functional skills will be assessed using the VABS-II Daily Living Domain Score. Uses standard score with a mean of 100 and SD of 15 with a range of 20-160. Higher score is better. Higher value in change indicates more improvement. |
| Caregiver Strain Questionnaire (CSQ) Subjective Internalizing Subscale Mean Score | Open Label: weeks 24, 48 | Caregiver questionnaire that assesses the impact of caring for the proband on caregiver and family. Each item on the subjective internalizing CSQ subscale is rated from 1 to 5. Then all items within the subscale are summed and the mean is determined based on the number of items in the subscale. Higher score indicates more caregiver strain. Lower value in change indicates more improvement. |
| Change in Vineland II Adaptive Behavior Scales (VABS-II) Communication Domain Score | Double-blind phase: baseline, week 24; Open Label: week 48 | Functional skills will be assessed using the VABS-II Communication Domain Score. Uses standard score with a mean of 100 and SD of 15 with a range of 20-160. Higher score is better. Higher value in change indicates more improvement. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oxytocin Nasal Spray Oxytocin
Oxytocin Nasal Spray: Each insufflation will deliver 8 IU or 24 IU of oxytocin. A maximum of 3 insufflations at a time will be required. Dosing will be flexible between 8 IU/day and 80 IU/day, typically in two divided doses delivered in the morning and in the afternoon. Doses will typically increase by 8 IU twice daily (BID) at week 2 and weeks 4 and 8 until achieving the target dose of 24 IU BID at week 8. Subsequently doses may be increased in 8 IU BID increments ONLY at each visit until a maximum dose of 40 IU BID is achieved.Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. During the open label phase after approximately March 2019 the study used only the 24 IU /0.10 ml formulation and the maximum dose was 72 IU per day. | 139 |
| Placebo Nasal Spray Placebo
Placebo Nasal Spray: This nasal spray will contain all of the ingredients that are in the active oxytocin spray in the same quantities, except there will be no oxytocin added to the solution. It will be packaged using the same container system as the active oxytocin nasal spray. Each bottle's label will have its own unique nonsequential randomly assigned number and not a lot number to facilitate masking. Dose titration will occur using exactly the same criteria and procedures as for active study drug. | 138 |
| Total | 277 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Open Label Eligible and Consented | Adverse Event | 6 | 1 |
| Open Label Eligible and Consented | Clinical Worsening | 4 | 2 |
| Open Label Eligible and Consented | Lost to Follow-up | 3 | 5 |
| Open Label Eligible and Consented | Withdrawal by Subject | 1 | 0 |
| Randomized to DB | Adverse Event | 5 | 2 |
| Randomized to DB | Clinical Worsening | 3 | 2 |
| Randomized to DB | Did not have a postbaseline ABC SW | 5 | 6 |
| Randomized to DB | Did not have baseline ABC-SW | 2 | 0 |
| Randomized to DB | Lost to Follow-up | 3 | 3 |
| Randomized to DB | Physician Decision | 1 | 2 |
| Randomized to DB | Withdrawal by Subject | 2 | 4 |
Baseline characteristics
| Characteristic | Total | Placebo Nasal Spray | Oxytocin Nasal Spray |
|---|---|---|---|
| Aberrant Behavior Checklist Social Withdrawal Subscale Score (ABC-SW) abc-SW (mean | 11.3 units on a scale STANDARD_DEVIATION 7.4 | 11.6 units on a scale STANDARD_DEVIATION 7.8 | 11.0 units on a scale STANDARD_DEVIATION 6.9 |
| Age, Continuous | 10.4 years STANDARD_DEVIATION 4.04 | 10.4 years STANDARD_DEVIATION 3.99 | 10.4 years STANDARD_DEVIATION 4.06 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 28 Participants | 15 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 249 Participants | 123 Participants | 126 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 23 Participants | 12 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 23 Participants | 14 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 23 Participants | 9 Participants | 14 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 204 Participants | 100 Participants | 104 Participants |
| Region of Enrollment United States | 277 Participants | 138 Participants | 139 Participants |
| Sex: Female, Male Female | 35 Participants | 18 Participants | 17 Participants |
| Sex: Female, Male Male | 242 Participants | 120 Participants | 122 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 146 | 0 / 144 | 1 / 127 | 0 / 122 |
| other Total, other adverse events | 120 / 146 | 120 / 144 | 91 / 127 | 92 / 122 |
| serious Total, serious adverse events | 2 / 146 | 1 / 144 | 4 / 127 | 0 / 122 |
Outcome results
Primary
Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity
The primary outcome is Change in Aberrant Behavior Checklist-Modified Social Withdrawal subscale- a measure of reciprocal social behaviors. ABC-mSW is a modification of the ABC-Lethargy subscale. The ABC-mSW consists of the sum of questions 5,12,16, 20, 23, 26, 30, 37, 40, 42, 43, 55, and 58. In contrast to the ABC-Lethargy subscale it eliminates question 3 (listless, sluggish, inactive), question 32 (sits or stands in one position for a long time), and question 53 (inactive, never moves spontaneously). Thirteen individual items are scored 0-3, therefore the range is 0-39. Higher score indicates lower social reciprocity. Repeated measures were obtained at baseline, weeks 4, 8, 12, 16, 20, 24.
Time frame: Least Mean Squares Double-blind phase: change from baseline to week 24
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxytocin Nasal Spray | Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity | Double-blind baseline to w4 | 8.81 score on a scale | Standard Error 0.39 |
| Oxytocin Nasal Spray | Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity | Double-blind baseline to w8 | 8.97 score on a scale | Standard Error 0.45 |
| Oxytocin Nasal Spray | Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity | Double-blind baseline-w12 | 7.48 score on a scale | Standard Error 0.43 |
| Oxytocin Nasal Spray | Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity | DB w0- w16 | 7.99 score on a scale | Standard Error 0.46 |
| Oxytocin Nasal Spray | Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity | DB w0- w20 | 7.81 score on a scale | Standard Error 0.05 |
| Oxytocin Nasal Spray | Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity | DB w0-w24 | 7.75 score on a scale | Standard Error 0.46 |
| Placebo Nasal Spray | Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity | DB w0- w20 | 7.75 score on a scale | Standard Error 0.45 |
| Placebo Nasal Spray | Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity | Double-blind baseline to w4 | 8.68 score on a scale | Standard Error 0.39 |
| Placebo Nasal Spray | Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity | DB w0- w16 | 8.04 score on a scale | Standard Error 0.46 |
| Placebo Nasal Spray | Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity | Double-blind baseline to w8 | 8.68 score on a scale | Standard Error 0.45 |
| Placebo Nasal Spray | Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity | DB w0-w24 | 8.05 score on a scale | Standard Error 0.46 |
| Placebo Nasal Spray | Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity | Double-blind baseline-w12 | 8.13 score on a scale | Standard Error 0.43 |
p-value: 0.503Mixed Models Analysis
Primary
Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity
The ABC-mSW is described above and involves 13 items reflecting lack of reciprocal interaction. Each item is scored from 0 (never shows behavior) to 3 (behavior is a major problem). The range is 0-39. Higher scores indicate worse reciprocal social functioning.
Time frame: Least mean squares for Open Label: Change between weeks 24-48
Population: Open Label phase participants in OLE FAS excluding 2 participants without usable ABC-sws (either w24 or at least one pw24 ABC-sw.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Oxytocin Nasal Spray | Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity | Open Label week 24 | 7.83 score on a scale |
| Oxytocin Nasal Spray | Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity | Open Label week 48 | 6.99 score on a scale |
| Placebo Nasal Spray | Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity | Open Label week 24 | 7.81 score on a scale |
| Placebo Nasal Spray | Change in Aberrant Behavior Checklist-Modified Social Withdrawal Subscale ABC-mSW, a Measure of Social Reciprocity | Open Label week 48 | 6.78 score on a scale |
p-value: 0.61Mixed Models Analysis
Secondary
Change in Sociability Factor (SF)
The Sociability Factor (SF) is a summed measure of the13 items of the ABC-SW and the 18 items of the Pervasive Development Disorders Behavior Inventory-Screening Version (PDDBI-SV).The PDDBI-SV assesses both adaptive social behaviors and social problems typical of ASD. The adaptive behaviors are reverse scored so that all the analyzed scores range from 0-performing in a neurotypical fashion to 3 typically performs in a way associated with ASD. the total # of items on this summed measure is 31 with a range from 0 to 93. More impaired social functioning indicated by higher scores. This measure was changed to a secondary outcome in the final statistical analysis plan.
Time frame: Double-blind phase: change in least means squares between week 0 & 24.
Population: Full Analysis Set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Oxytocin Nasal Spray | Change in Sociability Factor (SF) | DB w0-w8 | -5.99 score on a scale | Standard Error 0.66 |
| Oxytocin Nasal Spray | Change in Sociability Factor (SF) | DB w0-w16 | -6.82 score on a scale | Standard Error 0.7 |
| Oxytocin Nasal Spray | Change in Sociability Factor (SF) | DB w0-w4 | -5.57 score on a scale | Standard Error 0.69 |
| Oxytocin Nasal Spray | Change in Sociability Factor (SF) | DB w0-w20 | -7.24 score on a scale | Standard Error 0.88 |
| Oxytocin Nasal Spray | Change in Sociability Factor (SF) | DB w0-w12 | -6.40 score on a scale | Standard Error 0.66 |
| Oxytocin Nasal Spray | Change in Sociability Factor (SF) | DB w0-w24 | -7.66 score on a scale | Standard Error 0.78 |
| Oxytocin Nasal Spray | Change in Sociability Factor (SF) | DB w0 | 35.8 score on a scale | Standard Error 1.24 |
| Placebo Nasal Spray | Change in Sociability Factor (SF) | DB w0-w24 | -8.27 score on a scale | Standard Error 0.88 |
| Placebo Nasal Spray | Change in Sociability Factor (SF) | DB w0 | 36.1 score on a scale | Standard Error 1.28 |
| Placebo Nasal Spray | Change in Sociability Factor (SF) | DB w0-w4 | -5.81 score on a scale | Standard Error 0.69 |
| Placebo Nasal Spray | Change in Sociability Factor (SF) | DB w0-w8 | -6.30 score on a scale | Standard Error 0.66 |
| Placebo Nasal Spray | Change in Sociability Factor (SF) | DB w0-w12 | -6.79 score on a scale | Standard Error 0.66 |
| Placebo Nasal Spray | Change in Sociability Factor (SF) | DB w0-w16 | -7.28 score on a scale | Standard Error 0.71 |
| Placebo Nasal Spray | Change in Sociability Factor (SF) | DB w0-w20 | -7.77 score on a scale | Standard Error 0.88 |
Secondary
Change in Social Responsiveness Scale-2 (SRS-2) Social Motivation Subscale Score
The SRS-Social Motivation subscale was developed to provide a quantitative measure of social impairments typically observed in ASD in children 3-18 years. Reported as T-score with a range of 38-90 for both boys and girls. Higher score indicates more severe clinical condition. Lower value in change indicates more improvement.
Time frame: Double-blind phase: baseline, weeks 12, 24
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxytocin Nasal Spray | Change in Social Responsiveness Scale-2 (SRS-2) Social Motivation Subscale Score | Double-blind baseline to week 12 | -4.58 T-score | Standard Deviation 0.68 |
| Oxytocin Nasal Spray | Change in Social Responsiveness Scale-2 (SRS-2) Social Motivation Subscale Score | Double-blind baseline to week 24 | -4.49 T-score | Standard Deviation 0.7 |
| Placebo Nasal Spray | Change in Social Responsiveness Scale-2 (SRS-2) Social Motivation Subscale Score | Double-blind baseline to week 12 | -5.72 T-score | Standard Deviation 0.69 |
| Placebo Nasal Spray | Change in Social Responsiveness Scale-2 (SRS-2) Social Motivation Subscale Score | Double-blind baseline to week 24 | -5.42 T-score | Standard Deviation 0.7 |
Secondary
Change in Stanford Binet-5th Edition (SB-5) IQ Score
Cognitive skills will be assessed using the Stanford Binet-5th Edition (SB-5) (Roid). Acceptable IQ range is 47-153, with higher score being better. Higher change scores indicate more improvement.
Time frame: Double-blind phase: baseline to week 24
Population: Participants with scores collected at baseline and week 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin Nasal Spray | Change in Stanford Binet-5th Edition (SB-5) IQ Score | 0.40 score on a scale | Standard Deviation 11.64 |
| Placebo Nasal Spray | Change in Stanford Binet-5th Edition (SB-5) IQ Score | 1.0 score on a scale | Standard Deviation 10.84 |
Other Pre-specified
Caregiver Strain Questionnaire (CSQ) Subjective Internalizing Subscale Mean Score
Caregiver questionnaire that assesses the impact of caring for the proband on caregiver and family. Each item on the subjective internalizing CSQ subscale is rated from 1 to 5. Then all items within the subscale are summed and the mean is determined based on the number of items in the subscale. Higher score indicates more caregiver strain. Lower value in change indicates more improvement.
Time frame: Open Label: weeks 24, 48
Population: Full Analysis Set participants who entered double blind and have values at week 24 AND 48
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxytocin Nasal Spray | Caregiver Strain Questionnaire (CSQ) Subjective Internalizing Subscale Mean Score | Open Label week 24 | 2.96 mean score on a scale | Standard Deviation 0.99 |
| Oxytocin Nasal Spray | Caregiver Strain Questionnaire (CSQ) Subjective Internalizing Subscale Mean Score | Open Label week 48 | 2.97 mean score on a scale | Standard Deviation 0.99 |
| Placebo Nasal Spray | Caregiver Strain Questionnaire (CSQ) Subjective Internalizing Subscale Mean Score | Open Label week 24 | 2.85 mean score on a scale | Standard Deviation 1 |
| Placebo Nasal Spray | Caregiver Strain Questionnaire (CSQ) Subjective Internalizing Subscale Mean Score | Open Label week 48 | 2.85 mean score on a scale | Standard Deviation 0.97 |
Other Pre-specified
Change in Caregiver Strain Questionnaire (CSQ) Objective Subscale Score
Caregiver questionnaire that assesses the impact of caring for the proband on caregiver and family. CSQ subscale scores are ranged from 1 to 5. Higher score indicates more caregiver strain. Lower value in change indicates more improvement. The analysis directions for the instrument that are used in these analyses are the mean of all the responses in the scale or subscale.
Time frame: Double-blind phase: baseline, week 24; Open Label: week 48
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxytocin Nasal Spray | Change in Caregiver Strain Questionnaire (CSQ) Objective Subscale Score | Double-blind baseline to week 24 | -0.16 score on a scale | Standard Error 0.06 |
| Oxytocin Nasal Spray | Change in Caregiver Strain Questionnaire (CSQ) Objective Subscale Score | Open Label week 24 to week 48 | 0.13 score on a scale | Standard Error 0.06 |
| Placebo Nasal Spray | Change in Caregiver Strain Questionnaire (CSQ) Objective Subscale Score | Double-blind baseline to week 24 | -0.22 score on a scale | Standard Error 0.06 |
| Placebo Nasal Spray | Change in Caregiver Strain Questionnaire (CSQ) Objective Subscale Score | Open Label week 24 to week 48 | 0.44 score on a scale | Standard Error 0.08 |
Other Pre-specified
Change in Caregiver Strain Questionnaire (CSQ) Subjective Externalizing Subscale Score
Caregiver questionnaire that assesses the impact of caring for the proband on caregiver and family. CSQ subscale scores are ranged from 1 to 5. Higher score indicates more caregiver strain. Lower value in change indicates more improvement.
Time frame: Double-blind phase: baseline, week 24; Open Label: week 48
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxytocin Nasal Spray | Change in Caregiver Strain Questionnaire (CSQ) Subjective Externalizing Subscale Score | Double-blind baseline to week 24 | -0.08 score on a scale | Standard Error 0.04 |
| Oxytocin Nasal Spray | Change in Caregiver Strain Questionnaire (CSQ) Subjective Externalizing Subscale Score | Open Label week 24 to week 48 | 0.01 score on a scale | Standard Error 0.07 |
| Placebo Nasal Spray | Change in Caregiver Strain Questionnaire (CSQ) Subjective Externalizing Subscale Score | Double-blind baseline to week 24 | -0.04 score on a scale | Standard Error 0.04 |
| Placebo Nasal Spray | Change in Caregiver Strain Questionnaire (CSQ) Subjective Externalizing Subscale Score | Open Label week 24 to week 48 | 0 score on a scale | Standard Error 0.08 |
Other Pre-specified
Change in Caregiver Strain Questionnaire (CSQ) Subjective Internalizing Subscale Score
Caregiver questionnaire that assesses the impact of caring for the proband on caregiver and family. CSQ subscale scores are ranged from 1 to 5. with each item of the subscale having the same range, the sum of the items within the subscale are summed, and the mean score is determined (I.e. a single # between 1 and 5) and reported. Higher scores indicate more caregiver strain. Lower value in change indicates more improvement.
Time frame: Double-blind phase: baseline, week 24
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin Nasal Spray | Change in Caregiver Strain Questionnaire (CSQ) Subjective Internalizing Subscale Score | -0.16 score on a scale | Standard Error 0.07 |
| Placebo Nasal Spray | Change in Caregiver Strain Questionnaire (CSQ) Subjective Internalizing Subscale Score | -0.29 score on a scale | Standard Error 0.07 |
Other Pre-specified
Change in Clinical Global Impressions -Improvement Score (CGI-I)
The Clinical Global Impressions - Improvement score and Severity score, which is routinely used in pharmacologic clinical trials, will capture the study physician's global impression of response. scores of 1 and 2 are considered as a percentage of total subjects in arm
Time frame: Double blind phase: change from Baseline to week 12, and week 24. Open label phase change from week 24 to week 48
Population: full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oxytocin Nasal Spray | Change in Clinical Global Impressions -Improvement Score (CGI-I) | 64 percentage of participants in arm |
| Placebo Nasal Spray | Change in Clinical Global Impressions -Improvement Score (CGI-I) | 53 percentage of participants in arm |
Other Pre-specified
Change in Vineland II Adaptive Behavior Scales (VABS-II) Communication Domain Score
Functional skills will be assessed using the VABS-II Communication Domain Score. Uses standard score with a mean of 100 and SD of 15 with a range of 20-160. Higher score is better. Higher value in change indicates more improvement.
Time frame: Double-blind phase: baseline, week 24; Open Label: week 48
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxytocin Nasal Spray | Change in Vineland II Adaptive Behavior Scales (VABS-II) Communication Domain Score | Double-blind baseline to week 24 | 3.88 score on a scale | Standard Error 0.89 |
| Oxytocin Nasal Spray | Change in Vineland II Adaptive Behavior Scales (VABS-II) Communication Domain Score | Open Label week 24 to week 48 | 4.06 score on a scale | Standard Error 1.35 |
| Placebo Nasal Spray | Change in Vineland II Adaptive Behavior Scales (VABS-II) Communication Domain Score | Double-blind baseline to week 24 | 2.27 score on a scale | Standard Error 0.9 |
| Placebo Nasal Spray | Change in Vineland II Adaptive Behavior Scales (VABS-II) Communication Domain Score | Open Label week 24 to week 48 | 5.98 score on a scale | Standard Error 1.41 |
Other Pre-specified
Change in Vineland II Adaptive Behavior Scales (VABS-II) Composite Score
Functional skills including communication will be assessed using the VABS-II Adaptive Behavior Composite Score. Uses standard score with a mean of 100 and SD of 15 with a range of 20-160. Higher score is better. Higher value in change indicates more improvement.
Time frame: Double-blind phase: baseline, week 24
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin Nasal Spray | Change in Vineland II Adaptive Behavior Scales (VABS-II) Composite Score | 2.61 score on a scale | Standard Deviation 1.26 |
| Placebo Nasal Spray | Change in Vineland II Adaptive Behavior Scales (VABS-II) Composite Score | 1.50 score on a scale | Standard Deviation 1.27 |
Other Pre-specified
Change in Vineland II Adaptive Behavior Scales (VABS-II) Daily Living Domain Score
Functional skills will be assessed using the VABS-II Daily Living Domain Score. Uses standard score with a mean of 100 and SD of 15 with a range of 20-160. Higher score is better. Higher value in change indicates more improvement.
Time frame: Double-blind phase: baseline, week 24; Open Label: week 48
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxytocin Nasal Spray | Change in Vineland II Adaptive Behavior Scales (VABS-II) Daily Living Domain Score | Double-blind baseline to week 24 | 2.50 score on a scale | Standard Error 1.1 |
| Oxytocin Nasal Spray | Change in Vineland II Adaptive Behavior Scales (VABS-II) Daily Living Domain Score | Open Label week 24 to week 48 | 1.76 score on a scale | Standard Error 1.19 |
| Placebo Nasal Spray | Change in Vineland II Adaptive Behavior Scales (VABS-II) Daily Living Domain Score | Double-blind baseline to week 24 | 1.24 score on a scale | Standard Error 1.14 |
| Placebo Nasal Spray | Change in Vineland II Adaptive Behavior Scales (VABS-II) Daily Living Domain Score | Open Label week 24 to week 48 | 0.62 score on a scale | Standard Error 0.11 |
Other Pre-specified
Change in Vineland II Adaptive Behavior Scales (VABS-II) Socialization Domain Score
Functional skills will be assessed using the VABS-II Socialization Domain Score. Uses standard score with a mean of 100 and SD of 15 with a range of 20-160. Higher score is better. Higher value in change indicates more improvement.
Time frame: Double-blind phase: baseline, week 24; Open Label: week 48
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxytocin Nasal Spray | Change in Vineland II Adaptive Behavior Scales (VABS-II) Socialization Domain Score | Double-blind baseline to week 24 | 4.45 score on a scale | Standard Error 1.27 |
| Oxytocin Nasal Spray | Change in Vineland II Adaptive Behavior Scales (VABS-II) Socialization Domain Score | Open Label week 24 to week 48 | 1.59 score on a scale | Standard Error 1.11 |
| Placebo Nasal Spray | Change in Vineland II Adaptive Behavior Scales (VABS-II) Socialization Domain Score | Double-blind baseline to week 24 | 4.87 score on a scale | Standard Error 1.25 |
| Placebo Nasal Spray | Change in Vineland II Adaptive Behavior Scales (VABS-II) Socialization Domain Score | Open Label week 24 to week 48 | 0.54 score on a scale | Standard Error 1.1 |
Other Pre-specified
Reading Mind in the Eyes Test is an Objective Measures of the Extent to Which Verbal Participants With Rudimentary Knowledge of Emotion Names Are Able to Correctly Identify the Emotion Shown in a Black and White Picture of the Eyes and Nose of an Actor.
This computerized task consists of a series of pictures of eyes in which the participant needs to determine which emotion the eyes are expressing from 4 emotions listed along with the picture. The outcome is the % of pictures with correct emotion identified. The range is 0 to 100%. The larger percent identified correctly indicates better ability to perceive emotions. An increase or positive change indicates better ability to identify emotions since baseline.
Time frame: Double blind phase: change from Baseline and week 24. Note: only those who demonstrated understanding of these concepts were included in sample.
Population: only subjects who could define feelings from fluently verbal subgroup
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxytocin Nasal Spray | Reading Mind in the Eyes Test is an Objective Measures of the Extent to Which Verbal Participants With Rudimentary Knowledge of Emotion Names Are Able to Correctly Identify the Emotion Shown in a Black and White Picture of the Eyes and Nose of an Actor. | DB w0 | 51.1 percentage of correct responses | Standard Deviation 18.76 |
| Oxytocin Nasal Spray | Reading Mind in the Eyes Test is an Objective Measures of the Extent to Which Verbal Participants With Rudimentary Knowledge of Emotion Names Are Able to Correctly Identify the Emotion Shown in a Black and White Picture of the Eyes and Nose of an Actor. | DB w24 | 54.9 percentage of correct responses | Standard Deviation 14.02 |
| Placebo Nasal Spray | Reading Mind in the Eyes Test is an Objective Measures of the Extent to Which Verbal Participants With Rudimentary Knowledge of Emotion Names Are Able to Correctly Identify the Emotion Shown in a Black and White Picture of the Eyes and Nose of an Actor. | DB w0 | 48.2 percentage of correct responses | Standard Deviation 18.61 |
| Placebo Nasal Spray | Reading Mind in the Eyes Test is an Objective Measures of the Extent to Which Verbal Participants With Rudimentary Knowledge of Emotion Names Are Able to Correctly Identify the Emotion Shown in a Black and White Picture of the Eyes and Nose of an Actor. | DB w24 | 49.92 percentage of correct responses | Standard Deviation 13.84 |
Other Pre-specified
Social Responsiveness Scale-2 (SRS-2) Social Motivation Subscale Score
The SRS-Social Motivation subscale was developed to provide a quantitative measure of social impairments typically observed in ASD in children 3-18 years. Reported as T-score with a range of 38-90 for both boys and girls. Higher score indicates more severe clinical condition. Lower value in change indicates more improvement.
Time frame: Open Label: weeks 24, 48
Population: Open Label phase participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxytocin Nasal Spray | Social Responsiveness Scale-2 (SRS-2) Social Motivation Subscale Score | Open Label week 24 | 88.5 T-score | Standard Error 1.37 |
| Oxytocin Nasal Spray | Social Responsiveness Scale-2 (SRS-2) Social Motivation Subscale Score | Open Label week 48 | 87.9 T-score | Standard Error 1.83 |
| Placebo Nasal Spray | Social Responsiveness Scale-2 (SRS-2) Social Motivation Subscale Score | Open Label week 24 | 86.6 T-score | Standard Error 1.37 |
| Placebo Nasal Spray | Social Responsiveness Scale-2 (SRS-2) Social Motivation Subscale Score | Open Label week 48 | 83.0 T-score | Standard Error 1.81 |