AutismPhase 2NCT00490802
Intranasal Oxytocin in the Treatment of Autism
A Phase 2 study testing Oxytocin in people with Autism, run by Evdokia Anagnostou at 1 site in United States.
Trial summary
The purpose of this study is to learn whether or not the drug called oxytocin is helpful in improving mood and social functioning in adults with autism. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Autism
- What is being tested?
- Oxytocin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2006to Apr 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male or female outpatients 18 to 60 years of age.
- Meet Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. The diagnosis will be confirmed with Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule .
- Have a Clinician's Global Impression-Severity score ≥ 4 (moderately ill) at Screening and Baseline.
- If already receiving stable nonpharmacologic educational, behavioral, and/or dietary interventions, have continuous participation during the preceding 3 months prior to Screening and will not electively initiate new or modify ongoing interventions for the duration of the study.
- Have normal physical examination and laboratory test results at Screening. If abnormal, the finding(s) must be deemed clinically insignificant by the Investigators.
- The patient must be able to speak and understand English sufficiently to understand the nature of the study and to allow for the completion of all study assessments.
- Have a normal Intelligence Quotient (>70) supported by the Wechsler Abbreviated Scales of Intelligence.
Who cannot join
- Patients born prior to 35 weeks gestational age.
- Patients with any primary psychiatric diagnosis other than autism at Screening: a history of attention deficit hyperactivity disorder, bipolar disorder, psychosis, posttraumatic stress disorder, schizophrenia, or major depressive disorder.
- Patients with a medical history of neurological disease, including, but not limited to, epilepsy/seizure disorder (except simple febrile seizures), movement disorder, tuberous sclerosis, fragile X, and any other known genetic syndromes, or known abnormal magnetic resonance imaging/structural lesion of the brain.
- Pregnant female patients.
- Patients with a medical condition that might interfere with the conduct of the study, confound interpretation of the study results, or endanger their own well-being. Patients with evidence or history of malignancy or any significant hematological, endocrine, cardiovascular (including any rhythm disorder), respiratory, renal, hepatic, or gastrointestinal disease.
- Patients taking psychoactive medication(s) (e.g., stimulants, antidepressants, antipsychotics, antiepileptics, anxiolytics, clonidine).
Show all 9Show fewer
- Patients who plan to initiate or change nonpharmacologic interventions during the course of the study.
- Patients unable to tolerate venipuncture procedures for blood sampling.
- Patients who, in the Investigator's opinion, might not be suitable for the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Mount Sinai School of Medicine
New York, New York, 10029-6574
About this study
The purpose of this study is to learn whether or not the drug called oxytocin is helpful in improving mood and social functioning in adults with autism.
Read the detailed description
Autism is a developmental disorder characterized by abnormalities in speech and communication, impaired social functioning, and repetitive behaviors and restricted interests. A number of researchers have suggested that the neuropeptide oxytocin may be implicated in the etiology of autism.
Given the likely possibility of dysregulated oxytocin in autism, the goal of this pilot study is to investigate the long-term therapeutic effects of oxytocin in the treatment of autism. One practical issue with oxytocin is that it does not exist in a pill form. Only the intravenous form is available in the United States and this form may or may not pass the blood-brain barrier. In addition, intravenous oxytocin is not practical for treatment studies. One alternative is intranasal oxytocin; this form of administration is known to pass the blood-brain barrier, and it is easy for participants to self-administer. Although not available in the United States, we are in the process of receiving an Investigational New Drug exemption for its use and can import it from Europe.
Thus, this pilot investigation will explore daily intranasal oxytocin in the treatment of autism. Also, there are very few, if any, outcome measures to assess social functioning in the "real world" in the context of clinical trials; yet, this is a major target for intervention, especially in autism. Thus, a final goal of this study will be to explore the use of Event Contingent Recording to index changes in social functioning and affect. Event Contingent Recording is a methodology developed by personality/social psychologists, which allows participants to report on symptoms, affect, and behavior close in time to experience. In addition, to enabling more sensitive assessments, this methodology allows for the assessment of more diverse (e.g., at home versus work) and more detailed measurements of mood and behavior.
Finally, a portion of this study aims to perform gene expression profiling using fresh whole blood to explore the molecular mechanisms underlying oxytocin therapy and oxytocin efficacy in adults with high functioning autism or Asperger's syndrome. The systemic effects of oxytocin therapy and the molecular basis for a positive treatment response to oxytocin are not well understood. An understanding of the former may help predict those persons who may suffer side-effects from treatment and the latter may help provide easily accessible peripheral biomarkers that could predict treatment response.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OxytocinDrug
Also called Syntocinon
Intranasal Oxytocin
PlaceboDrug
Placebo Comparator
| Study group | Role | What they receive |
|---|---|---|
| Intranasal Oxytocin | Experimental | Subjects were given 24 IU intranasal oxytocin twice daily, in the morning and afternoon for 6 weeks. Receives: Drug: Oxytocin |
| Placebo | Placebo comparator | Subjects were given placebo twice daily, in the morning and afternoon for 6 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Global Impressions Scale - Improvement - Social
The Clinical Global Impressions Scale - Improvement - Social is a well validated measure employing a 7-point scale of clinical global impression of improvement ( 1- very much improved, 2 - much improved, 3 - minimally improved, 4 - no change, 5 - minimally worse, 6 - much worse, 7 - very much worse) that the clinician fills out after considering all the available information on the participant including the parent history, the examination in clinic, reports from the school and other sources. Therefore the score is filtered through the judgment of the clinician evaluator.
The Week 6 Improvement Ratings were used to categorize patients as clinically improved (≤2) or not (>2). Sixteen of the 19 patients (84%) had data at Week 6. For the remaining three subjects, Week 6 ratings were imputed using expectation-maximization methods and the earlier Clinical Global Impression ratings. In all three cases the imputed ratings were >2 and the patients were classified as not improved.
Measured: 6 Weeks
Repetitive Behavior Scale - Revised
The Repetitive Behavior Scale - Revised was developed to capture the breadth of repetitive behaviors that are specific to autism and is a parent report measure. In particular, it consists of 43-items that tap six repetitive behavior subtypes: Stereotyped, Self-injurious, Compulsive, Ritualistic, Sameness, and Restricted Interests.
Two scores were calculated (higher-order vs. lower-order repetitive behaviors) in an effort to decrease the number of variables analyzed. This is based on previous factor analysis that produced these two factors: higher order (ritualistic, sameness, compulsive and restricted subscales) and lower order (stereotypy and self-injury).
- The higher order behaviors have 29 items that can be endorsed with a maximum score of 87 and a minimum score of 0
- The lower order behaviors have 14 items that can be endorsed, with a maximum score of 42 and a minimum score of 0
In both cases, a lower score represents a positive response.
Measured: 6 Weeks
Diagnostic Analysis of Nonverbal Accuracy, Paralanguage Test
The Diagnostic Analysis of Nonverbal Accuracy is a measure of emotion recognition across multiple modalities. It consists of five subtests: the Adult Facial Expression Test, the Child Facial Expression Test, the Adult Paralanguage Test, the Child Paralanguage Test, and the Adult Posture Test. The Diagnostic Analysis of Nonverbal Accuracy has established reliability and validity for children as young as 3 and adults as old as 100. The subtests of the test vary on four basic core emotions: happiness, sadness, anger, and fear, and the test provides measures of both high intensity and low intensity emotional reactions. We utilized both the Child Paralanguage and Adult Paralanguage Tests, therefore the minimum score that can be obtained is 0 and the maximum is 48. A higher score represents a positive response.
Measured: 6 Weeks
Secondary outcomes (2)
Yale-Brown Obsessive-Compulsive Scale
The Yale-Brown Obsessive-Compulsive Scale is a clinician-rated questionnaire measuring the time spent, distress, interference, resistance, and control in relation to obsessions and compulsions based on a 5-point scale. This scale has excellent reliability and validity and is used as the gold standard to measure treatment challenges in all Obsessive-Compulsive Disorder clinical trials. The Yale-Brown Obsessive-Compulsive Scale Compulsion Subscale has been shown to be a reliable and valid scale in Autism Spectrum Disorder, and in measuring change in treatment studies of autism. The minimum score that can be obtained is 0 and the maximum score is 20. A lower score represents a positive response.
Measured: 6 Weeks
Social Responsiveness Scale
The Social Responsiveness Scale has been developed to measure autism related symptoms and focuses more on social function than social cognition. The Social Responsiveness Scale has been modified for adults by and we have obtained permission to use the adult scale, although it is not commercially available yet. The Social Responsiveness Scale measures social behaviors such as social awareness, information processing, and social motivation and yields a quantitative score that has been useful in endophenotype studies of Autism Spectrum Disorder. The minimum score that can be obtained is a 0 and the maximum raw score for subscales is 66, maximum total raw score is 153. A lower score represents a positive response.
Measured: 6 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2007 (estimated)
- Study startJun 2006
- Primary completionSep 2011
- Study completionApr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for AutismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Evdokia Anagnostou
- Collaborators
- Icahn School of Medicine at Mount Sinai
- Responsible party
- Sponsor-investigator, Evdokia Anagnostou, Anagnostou, Evdokia, M.D.
- Investigators
- Evdokia Anagnostou, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00490802
- Sponsor's protocol ID
- 06-0230 0001 02 PS
- Status last verified
- Oct 2015
- First submitted
- 22 Jun 2007
- Last updated
- 23 Oct 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.
PubMed 37811711Anagnostou E, Soorya L, Chaplin W, Bartz J, Halpern D, Wasserman S, Wang AT, Pepa L, Tanel N, Kushki A, Hollander E. Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: a randomized controlled trial. Mol Autism. 2012 Dec 5;3(1):16. doi: 10.1186/2040-2392-3-16.
PubMed 23216716
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intranasal Oxytocin in the Treatment of Autism
- ClinicalTrials.gov ID
- NCT00490802
- Acronym / sponsor ID
- 06-0230 0001 02 PS
- Conditions
- Autism
- Keywords
- Autism, Treatment, Oxytocin, Adults, Autism Spectrum Disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Evdokia Anagnostou
- Collaborators
- Icahn School of Medicine at Mount Sinai
- Study start
- Jun 2006
- Primary completion
- Sep 2011 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 25 Jun 2007 (estimated)
- Results
- Posted 5 Nov 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to learn whether or not the drug called oxytocin is helpful in improving mood and social functioning in adults with autism.
Detailed description
Autism is a developmental disorder characterized by abnormalities in speech and communication, impaired social functioning, and repetitive behaviors and restricted interests. A number of researchers have suggested that the neuropeptide oxytocin may be implicated in the etiology of autism.
Given the likely possibility of dysregulated oxytocin in autism, the goal of this pilot study is to investigate the long-term therapeutic effects of oxytocin in the treatment of autism. One practical issue with oxytocin is that it does not exist in a pill form. Only the intravenous form is available in the United States and this form may or may not pass the blood-brain barrier. In addition, intravenous oxytocin is not practical for treatment studies. One alternative is intranasal oxytocin; this form of administration is known to pass the blood-brain barrier, and it is easy for participants to self-administer. Although not available in the United States, we are in the process of receiving an Investigational New Drug exemption for its use and can import it from Europe.
Thus, this pilot investigation will explore daily intranasal oxytocin in the treatment of autism. Also, there are very few, if any, outcome measures to assess social functioning in the "real world" in the context of clinical trials; yet, this is a major target for intervention, especially in autism. Thus, a final goal of this study will be to explore the use of Event Contingent Recording to index changes in social functioning and affect. Event Contingent Recording is a methodology developed by personality/social psychologists, which allows participants to report on symptoms, affect, and behavior close in time to experience. In addition, to enabling more sensitive assessments, this methodology allows for the assessment of more diverse (e.g., at home versus work) and more detailed measurements of mood and behavior.
Finally, a portion of this study aims to perform gene expression profiling using fresh whole blood to explore the molecular mechanisms underlying oxytocin therapy and oxytocin efficacy in adults with high functioning autism or Asperger's syndrome. The systemic effects of oxytocin therapy and the molecular basis for a positive treatment response to oxytocin are not well understood. An understanding of the former may help predict those persons who may suffer side-effects from treatment and the latter may help provide easily accessible peripheral biomarkers that could predict treatment response.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intranasal Oxytocin | Experimental | Drug: OxytocinSubjects were given 24 IU intranasal oxytocin twice daily, in the morning and afternoon for 6 weeks. |
| Placebo | Placebo comparator | Drug: PlaceboSubjects were given placebo twice daily, in the morning and afternoon for 6 weeks. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Male or female outpatients 18 to 60 years of age.
- Meet Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. The diagnosis will be confirmed with Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule .
- Have a Clinician's Global Impression-Severity score ≥ 4 (moderately ill) at Screening and Baseline.
- If already receiving stable nonpharmacologic educational, behavioral, and/or dietary interventions, have continuous participation during the preceding 3 months prior to Screening and will not electively initiate new or modify ongoing interventions for the duration of the study.
- Have normal physical examination and laboratory test results at Screening. If abnormal, the finding(s) must be deemed clinically insignificant by the Investigators.
Key exclusion criteria (9 listed)
- Patients born prior to 35 weeks gestational age.
- Patients with any primary psychiatric diagnosis other than autism at Screening: a history of attention deficit hyperactivity disorder, bipolar disorder, psychosis, posttraumatic stress disorder, schizophrenia, or major depressive disorder.
- Patients with a medical history of neurological disease, including, but not limited to, epilepsy/seizure disorder (except simple febrile seizures), movement disorder, tuberous sclerosis, fragile X, and any other known genetic syndromes, or known abnormal magnetic resonance imaging/structural lesion of the brain.
- Pregnant female patients.
- Patients with a medical condition that might interfere with the conduct of the study, confound interpretation of the study results, or endanger their own well-being. Patients with evidence or history of malignancy or any significant hematological, endocrine, cardiovascular (including any rhythm disorder), respiratory, renal, hepatic, or gastrointestinal disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OxytocinAlso: SyntocinonIntranasal Oxytocin | Drug | Intranasal Oxytocin |
| PlaceboPlacebo Comparator | Drug | Placebo |
Primary outcome
Clinical Global Impressions Scale - Improvement - Social
Time frame: 6 Weeks
The Clinical Global Impressions Scale - Improvement - Social is a well validated measure employing a 7-point scale of clinical global impression of improvement ( 1- very much improved, 2 - much improved, 3 - minimally improved, 4 - no change, 5 - minimally worse, 6 - much worse, 7 - very much worse) that the clinician fills out after considering all the available information on the participant including the parent history, the examination in clinic, reports from the school and other sources. Therefore the score is filtered through the judgment of the clinician evaluator. The Week 6 Improvement Ratings were used to categorize patients as clinically improved (≤2) or not (>2). Sixteen of the 19 patients (84%) had data at Week 6. For the remaining three subjects, Week 6 ratings were imputed using expectation-maximization methods and the earlier Clinical Global Impression ratings. In all three cases the imputed ratings were >2 and the patients were classified as not improved.
Repetitive Behavior Scale - Revised
Time frame: 6 Weeks
The Repetitive Behavior Scale - Revised was developed to capture the breadth of repetitive behaviors that are specific to autism and is a parent report measure. In particular, it consists of 43-items that tap six repetitive behavior subtypes: Stereotyped, Self-injurious, Compulsive, Ritualistic, Sameness, and Restricted Interests. Two scores were calculated (higher-order vs. lower-order repetitive behaviors) in an effort to decrease the number of variables analyzed. This is based on previous factor analysis that produced these two factors: higher order (ritualistic, sameness, compulsive and restricted subscales) and lower order (stereotypy and self-injury). 1. The higher order behaviors have 29 items that can be endorsed with a maximum score of 87 and a minimum score of 0 2. The lower order behaviors have 14 items that can be endorsed, with a maximum score of 42 and a minimum score of 0 In both cases, a lower score represents a positive response.
Diagnostic Analysis of Nonverbal Accuracy, Paralanguage Test
Time frame: 6 Weeks
The Diagnostic Analysis of Nonverbal Accuracy is a measure of emotion recognition across multiple modalities. It consists of five subtests: the Adult Facial Expression Test, the Child Facial Expression Test, the Adult Paralanguage Test, the Child Paralanguage Test, and the Adult Posture Test. The Diagnostic Analysis of Nonverbal Accuracy has established reliability and validity for children as young as 3 and adults as old as 100. The subtests of the test vary on four basic core emotions: happiness, sadness, anger, and fear, and the test provides measures of both high intensity and low intensity emotional reactions. We utilized both the Child Paralanguage and Adult Paralanguage Tests, therefore the minimum score that can be obtained is 0 and the maximum is 48. A higher score represents a positive response.
2 secondary outcomes
Yale-Brown Obsessive-Compulsive Scale
Time frame: 6 Weeks
Social Responsiveness Scale
Time frame: 6 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37811711Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.
- Derived from this study: PubMed 23216716Anagnostou E, Soorya L, Chaplin W, Bartz J, Halpern D, Wasserman S, Wang AT, Pepa L, Tanel N, Kushki A, Hollander E. Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: a randomized controlled trial. Mol Autism. 2012 Dec 5;3(1):16. doi: 10.1186/2040-2392-3-16.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Evdokia Anagnostou, MD principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Oxytocin in people with Autism, run by Evdokia Anagnostou at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Nov 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Global Impressions Scale - Improvement - Social (time frame: 6 Weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00490802, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2015.