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| Name | Class |
|---|---|
| Autism Speaks | OTHER |
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The investigators propose to conduct this pilot study to evaluate oxytocin as a supplemental treatment for improving social difficulties in individuals with autism.
The proposed pilot study is an essential first step toward rigorously evaluating oxytocin treatment of individuals with autism. The biologic actions of oxytocin on social cognition and prosocial behaviors and the clinical, genetic and epigenetic evidence for involvement of the oxytocin system in the pathophysiology of some cases of autism strongly suggest that supplemental oxytocin therapy could significantly improve the social disabilities involved in autism. Many people feel that these social difficulties are the most characteristic and central feature of autism. Overall, this study aims to determine the tolerability, accessibility, and feasibility of an oxytocin pilot study.
This study will consent up to 30 subjects in order to randomize up to 25 subjects into a 2-month (8 weeks) randomized double-blind, placebo-controlled initial treatment period, a subsequent 2-month (8 weeks) period in which all participants receive oxytocin, and up to three post-treatment visits that occur at week 28 (±2 weeks),an interim visit anytime between week 16 and week 76 only for those patients who plan to start oxytocin on their own outside of study treatment and who will experience a lag time between week 16 (end of open label treatment) and when outside oxytocin treatment will begin, and some time before week 76. The investigators hope that this study will help to inform future study designs in determining whether a short term or long term treatment trial is necessary to observe significant effects. This will also help to develop systematic preliminary safety measures.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Intervention: Drug: placebo |
|
| Oxytocin | Active Comparator | Intervention: Drug: Syntocinon® Nasal Spray |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oxytocin | Drug | Subjects will use the Syntocinon® Nasal Spray (oxytocin) twice daily for 8 weeks if they are randomized to that arm in the Randomized Phase. All subjects will use the Syntocinon® Nasal Spray twice daily for 8 weeks in the Open Label Phase. Subjects ages 3-10 years old will be titrated up to a maximum dose of 24 International units (IU). Subjects ages 11-17 years old will be titrated up to a maximum dose of 32IU. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Could Tolerate Twice Daily Oxytocin | This study will help to determine tolerability of intranasal oxytocin treatment in children with autism by measuring the ability of at least 80% of the sample to tolerate twice daily intranasal administration of oxytocin. | Week 0 to week 8 |
| Number of Participants Who Could Tolerate Twice Daily Oxytocin | This study will help to determine tolerability of intranasal oxytocin treatment in children with autism by measuring the ability of at least 80% of the sample to tolerate twice daily intranasal administration of oxytocin. | Week 0 to week 16 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Mean Plasma Oxytocin Level During Period 1 - Double Blind Phase | Blood samples will be collected to obtain proof of concept data regarding changes in afternoon plasma oxytocin levels | Week 0 to week 8 |
| Change in Mean Weight |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Linmarie Sikich, M.D. | University of North Carolina, Chapel Hill | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of North Carolina Chapel Hill | Chapel Hill | North Carolina | 27599 | United States |
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This study is a 2 sequence (arm) study with 2 periods - double-blind (0-8 weeks) and open label (8-16 weeks). The sequences are 1: oxytocin-oxytocin and 2: placebo-oxytocin. 1 participant from sequence 1 did not enter period 2 due to withdrawal due to adverse events.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sequence 1: Oxytocin-oxytocin | 8 weeks of double blind oxytocin followed by 8 weeks of open label oxytocin |
| FG001 | jSequence 2: Placebo-oxytocin | 8 weeks of of double blind placebo followed by 8 weeks of open-label oxytocin; this is the control group |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1: Double Blind Treatment |
|
| ||||||||||||||||||
| Period 2: Open Label Treatment |
|
The one participant in the oxytocin group who dropped out after 2 days is not included in the demographics or outcome analyses since no post baseline data other than AEs was obtained. This participant is included in the AE analysis.
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| ID | Title | Description |
|---|---|---|
| BG000 | Sequence 2:Placebo-oxytocin | Intervention: Drug: placebo Placebo: Placebo Nasal Spray |
| BG001 | Sequence 1: Oxytocin-oxytocin | Intervention: Drug: Syntocinon® Nasal Spray Oxytocin: Subjects will use the Syntocinon® Nasal Spray (oxytocin) twice daily for 8 weeks if they are randomized to that arm in the Randomized Phase. All subjects will use the Syntocinon® Nasal Spray twice daily for 8 weeks in the Open Label Phase. Subjects ages 3-10 years old will be titrated up to a maximum dose of 24 international units (IU). Subjects ages 11-17 years old will be titrated up to a maximum dose of 32IU. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants Who Could Tolerate Twice Daily Oxytocin | This study will help to determine tolerability of intranasal oxytocin treatment in children with autism by measuring the ability of at least 80% of the sample to tolerate twice daily intranasal administration of oxytocin. | This is over period 1, the double blind phase (week 0 to week 8) only | Posted | Count of Participants | Participants | Week 0 to week 8 |
|
Period 1 0-8 weeks comparing sequence 1 and 2, Period 2 comparing sequence1 and 2
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Sequence 1: Oxytocin:Oxytocin Period 1weeks 0-8 | Intervention: Drug: Syntocinon® Nasal Spray Oxytocin: Subjects will use the Syntocinon® Nasal Spray (oxytocin) twice daily for 8 weeks if they are randomized to that arm in the Randomized Phase. All subjects will use the Syntocinon® Nasal Spray twice daily for 8 weeks in the Open Label Phase. Subjects ages 3-10 years old will be titrated up to a maximum dose of 24IU. Subjects ages 11-17 years old will be titrated up to a maximum dose of 32IU. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Croup | Respiratory, thoracic and mediastinal disorders | MedDRA (11.0) | Systematic Assessment | unanticipated, unrelated |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| # of participants with any adverse event | General disorders | MedDRA (11.0) | Systematic Assessment |
This was a very small study with a very heterogeneous sample. Further the two groups included very different proportions of intellectually disabled non-verbal participants which may influence assessment of benefit.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Linmarie Sikich, MD | Duke University Center for Autism and Brain Development | 9196810026 | linmarie.sikich@duke.edu |
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| ID | Term |
|---|---|
| D001321 | Autistic Disorder |
| ID | Term |
|---|---|
| D000067877 | Autism Spectrum Disorder |
| D002659 | Child Development Disorders, Pervasive |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D010121 | Oxytocin |
| ID | Term |
|---|---|
| D010909 | Pituitary Hormones, Posterior |
| D010907 | Pituitary Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
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|
|
| Placebo | Drug | Placebo Nasal Spray |
|
changes during period 1
| between weeks 0 and 8 |
| Change in Mean Total Social Social Responsiveness Scale (SRS) T-score | The 65-item SRS is a standardized measure of the core symptoms of autism. Each item is scored on a 4-point Likert scale. The raw score of each individual item is summed to create a total raw score. The total raw score is then translated into a total T-scores (which are the equivalent of standard scores). Total T-scores results are as follows: 59 and below: within normal limits, 60-65: Mild range of impairment 66-75: Moderate range of impairment 76 or higher: Severe range of impairment. | 0-8 weeks, blinded treatment, period 1 |
| Change in Mean Autism Diagnostic Observation Schedule (ADOS) Total Score | The ADOS is a semi-structured assessment used to assess and diagnose individuals suspected of having autism of varying ages, developmental levels, and language skills (from no speech to verbally fluent). The ADOS includes four modules, each requiring just 35-40 minutes to administer. The individual being evaluated is given just one of 4 modules, depending on his or her expressive language level and chronological age. The rater will observe social and communication behaviors during various activities in the appropriate module. A rater then uses a 0-3 scale to rate each type of behavior. A select number of individual items will be summed for a total score representing communication and reciprocal social interaction. In scoring all 3's are collapsed to a 2. A higher score indicates more severe impairment. Ranges of scores are as follows: Module 1: 0-24, Module 2: 0-24, Module 3: 0-22, Module 4: 0-22. | Baseline to 16 Weeks |
| Change in Mean Aberrant Behavior Checklist (ABC)-Social Withdrawal Subscale Score Over Both Periods | Efficacy measures included the Aberrant Behavior Checklist -Social Withdrawal subscale scor. The ABC which focuses on problem behaviors in five subdomains, including irritability, attention, repetitive behaviors, unusual speech, and lethargy. A modified version of the lethargy subscale was used. Typically the Lethargy subscale includes 16 items, however, for our purposes 3 items that were specifically related to lethargy (i.e.: listlessness) were removed so that the focus could primarily be on aberrant social behavior. Differences in only the Social Withdrawal domain were assessed.The is the sum of items, each rated among 0 = Not at all; 1 = Slight in degree; 2 = Moderately serious; and 3 = Severe in degree. The ABC- Social Withdrawal total score ranges from 0 to 39. Higher values represent greater severity of illness. | Baseline to 16 Weeks |
| Change in Mean Pervasive Developmental Disorder Behavior Inventory - Screening Version (PDDBI-SV) Total Score Over Both Periods | The PDDBI-SV examines both adaptive and maladaptive behaviors related to autism. It has normative scores for children between 2-11 years. For children 12 years and older, the norms (11 years, 11 months) will be used. Each item is scored on a scale from 0-3. For the first 9 items, the total of individual items is summed. For items 10-18, the scores are reversed and then summed (i.e.: 0=3, 1 =2, 2=2, 3 = 0). Then the total of 0-9 and then the reversed scored items 10-18 are summed for a final total score. Higher scores indicate more impairment. The range of total scores is 0-54. ASD/Social deficits unlikely: 0-6, More information needed/borderline: 7-10, autism spectrum disorder (ASD)/social deficits likely (mild):11-14, ASD/social deficits likely (moderate): 15-29, ASD/social deficits likely (severe): 30-37, ASD/social deficits likely (extreme): 38 or higher. | Baseline to 16 Weeks |
| Change in Mean Systolic Blood Pressure During Period 1 | Change in mean systolic blood pressure during double blind phase | Week 0 to 8 |
| Mean Change in Prolactin Levels Over Period 1 | Serum prolactin levels were collected and analyzed in participants | Week 0 to 8 |
| Mean Change in Temperature During Period 1 | Temperature was collected on each participant via oral or temporal thermometer. The mean change in each group was assessed. | Week 0 to 8 |
| NOT COMPLETED |
|
|
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Non-verbal | Count of Participants | Participants |
|
| Intelligence Quotient (IQ) <70 | Count of Participants | Participants |
|
|
|
|
| Primary | Number of Participants Who Could Tolerate Twice Daily Oxytocin | This study will help to determine tolerability of intranasal oxytocin treatment in children with autism by measuring the ability of at least 80% of the sample to tolerate twice daily intranasal administration of oxytocin. | all participants who recieved oxytocin at any time | Posted | Count of Participants | Participants | Week 0 to week 16 |
|
|
|
| Secondary | Change in Mean Plasma Oxytocin Level During Period 1 - Double Blind Phase | Blood samples will be collected to obtain proof of concept data regarding changes in afternoon plasma oxytocin levels | participants with oxytocin plasma levels at baseline and week 8 | Posted | Mean | Standard Deviation | picograms/mL (pg/mL) | Week 0 to week 8 |
|
|
|
| Secondary | Change in Mean Weight | changes during period 1 | The subject who discontinued after 2 days did not have repeat assessments and is excluded from these analyses | Posted | Mean | Standard Error | pounds | between weeks 0 and 8 |
|
|
|
| Secondary | Change in Mean Total Social Social Responsiveness Scale (SRS) T-score | The 65-item SRS is a standardized measure of the core symptoms of autism. Each item is scored on a 4-point Likert scale. The raw score of each individual item is summed to create a total raw score. The total raw score is then translated into a total T-scores (which are the equivalent of standard scores). Total T-scores results are as follows: 59 and below: within normal limits, 60-65: Mild range of impairment 66-75: Moderate range of impairment 76 or higher: Severe range of impairment. | All participants with at least one post baseline assessment, 1 person from sequence 1 discontinued due to no post baseline measures | Posted | Mean | Standard Error | T-scores | 0-8 weeks, blinded treatment, period 1 |
|
|
|
|
| Secondary | Change in Mean Autism Diagnostic Observation Schedule (ADOS) Total Score | The ADOS is a semi-structured assessment used to assess and diagnose individuals suspected of having autism of varying ages, developmental levels, and language skills (from no speech to verbally fluent). The ADOS includes four modules, each requiring just 35-40 minutes to administer. The individual being evaluated is given just one of 4 modules, depending on his or her expressive language level and chronological age. The rater will observe social and communication behaviors during various activities in the appropriate module. A rater then uses a 0-3 scale to rate each type of behavior. A select number of individual items will be summed for a total score representing communication and reciprocal social interaction. In scoring all 3's are collapsed to a 2. A higher score indicates more severe impairment. Ranges of scores are as follows: Module 1: 0-24, Module 2: 0-24, Module 3: 0-22, Module 4: 0-22. | 1 patient without post baseline measures is not included | Posted | Mean | Standard Error | scores on a scale | Baseline to 16 Weeks |
|
|
|
| Secondary | Change in Mean Aberrant Behavior Checklist (ABC)-Social Withdrawal Subscale Score Over Both Periods | Efficacy measures included the Aberrant Behavior Checklist -Social Withdrawal subscale scor. The ABC which focuses on problem behaviors in five subdomains, including irritability, attention, repetitive behaviors, unusual speech, and lethargy. A modified version of the lethargy subscale was used. Typically the Lethargy subscale includes 16 items, however, for our purposes 3 items that were specifically related to lethargy (i.e.: listlessness) were removed so that the focus could primarily be on aberrant social behavior. Differences in only the Social Withdrawal domain were assessed.The is the sum of items, each rated among 0 = Not at all; 1 = Slight in degree; 2 = Moderately serious; and 3 = Severe in degree. The ABC- Social Withdrawal total score ranges from 0 to 39. Higher values represent greater severity of illness. | population of participants with all data available for mixed models analysis no data carried forward | Posted | Mean | Standard Error | scores on a scale | Baseline to 16 Weeks |
|
|
|
|
| Secondary | Change in Mean Pervasive Developmental Disorder Behavior Inventory - Screening Version (PDDBI-SV) Total Score Over Both Periods | The PDDBI-SV examines both adaptive and maladaptive behaviors related to autism. It has normative scores for children between 2-11 years. For children 12 years and older, the norms (11 years, 11 months) will be used. Each item is scored on a scale from 0-3. For the first 9 items, the total of individual items is summed. For items 10-18, the scores are reversed and then summed (i.e.: 0=3, 1 =2, 2=2, 3 = 0). Then the total of 0-9 and then the reversed scored items 10-18 are summed for a final total score. Higher scores indicate more impairment. The range of total scores is 0-54. ASD/Social deficits unlikely: 0-6, More information needed/borderline: 7-10, autism spectrum disorder (ASD)/social deficits likely (mild):11-14, ASD/social deficits likely (moderate): 15-29, ASD/social deficits likely (severe): 30-37, ASD/social deficits likely (extreme): 38 or higher. | used only subjects with all data points no data carried forward | Posted | Mean | Standard Error | scores on a scale | Baseline to 16 Weeks |
|
|
|
| Secondary | Change in Mean Systolic Blood Pressure During Period 1 | Change in mean systolic blood pressure during double blind phase | The one subject who discontinued at week 1 did not have follow up data to include in the analysis. | Posted | Mean | Standard Error | millimeters of mercury (mmHg) | Week 0 to 8 |
|
|
|
| Secondary | Mean Change in Prolactin Levels Over Period 1 | Serum prolactin levels were collected and analyzed in participants | Posted | Mean | Standard Error | nanograms per milliliter (ng/mL) | Week 0 to 8 |
|
|
|
| Secondary | Mean Change in Temperature During Period 1 | Temperature was collected on each participant via oral or temporal thermometer. The mean change in each group was assessed. | Posted | Mean | Standard Error | degrees fahrenheit | Week 0 to 8 |
|
|
|
| 0 |
| 12 |
| 1 |
| 12 |
| 12 |
| 12 |
| EG001 | Sequence 2: Placebo: Oxytocin Period 1 Weeks 0-8 | Intervention: Drug: placebo Placebo: Placebo Nasal Spray | 0 | 13 | 0 | 13 | 10 | 13 |
| EG002 | Sequence 1: Oxytocin:Oxytocin Period 2, Weeks 8-16 | evaluates longer term adverse events with oxytocin | 0 | 11 | 0 | 24 | 8 | 11 |
| EG003 | Sequence 2: Placebo:Oxytocin Period 2 | evaluates acute exposure to oxytocin in sequence 2 participants | 0 | 13 | 0 | 13 | 12 | 13 |
|
| # with moderate adverse event | General disorders | MedDRA (11.0) | Systematic Assessment |
|
| # with severe adverse event | General disorders | MedDRA (11.0) | Systematic Assessment |
|
| insomnia | Nervous system disorders | MedDRA (11.0) | Systematic Assessment | includes initial, midcycle and terminal of any severity |
|
| Anger or irritability | Psychiatric disorders | MedDRA (11.0) | Systematic Assessment | any severity |
|
| oppositional | Psychiatric disorders | MedDRA (11.0) | Systematic Assessment | any severity |
|
| mood lability | Psychiatric disorders | MedDRA (11.0) | Systematic Assessment | any severity |
|
| # who withdrew due to AE | General disorders | MedDRA (11.0) | Systematic Assessment |
|
| Aggression | Psychiatric disorders | MedDRA (11.0) | Systematic Assessment | any severity |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (11.0) | Systematic Assessment | any severity |
|
| Agitation | Nervous system disorders | MedDRA (11.0) | Systematic Assessment | anyseverity |
|
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| D006730 |
| Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |