Oxytocin Nasal Spray for Autism

(BOX Trial)

Recruiting at 1 trial location

Overseen By Sarah Smith, DNP

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must not be taking: Bone medications

Disqualifiers: Fragile X, Tuberous sclerosis, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 21

Duration: 12 months

96 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if giving oxytocin through a nasal spray can improve bone health in children with autism. Children with autism often have weaker bones and lower levels of oxytocin. The study aims to see if oxytocin can help make their bones stronger. Oxytocin has been investigated for its potential to treat social deficits in autism spectrum disorders, with various studies exploring its effects on social behavior and brain function.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those taking medications that may impact bone health, except for calcium or vitamin D supplements.

What data supports the effectiveness of the drug oxytocin nasal spray for autism?

Research suggests that oxytocin nasal spray may help improve social interaction in children with autism, as one study found significant improvements in social responsiveness compared to a placebo. However, the effectiveness of oxytocin for autism is still being explored, and larger trials are needed to confirm these findings. ^{1 2 3 4 5}

Is intranasal oxytocin nasal spray safe for humans?

Intranasal oxytocin nasal spray is generally considered safe for humans, with common mild side effects like nasal discomfort, tiredness, irritability, diarrhea, and skin irritation. Severe side effects are rare, and studies suggest it is well tolerated in both children and adults. ^{1 2 6 7 8}

How is the oxytocin nasal spray different from other autism treatments?

The oxytocin nasal spray is unique because it targets social deficits in autism by delivering oxytocin directly to the brain through the nose, which is different from other treatments that may not focus on these core symptoms. Additionally, there are no approved drugs specifically for treating the core symptoms of autism, making this approach novel. ^{1 2 3 4 9}

Research Team

Elizabeth A Lawson, MD

Principal Investigator

Neuroendocrine Unit Massachusetts General Hospital

Eligibility Criteria

This trial is for children aged 6-18 with Autism Spectrum Disorder who can give informed assent/consent and have a parent/guardian to consent. They must be within the 10th-85th BMI percentiles, not on certain medications or have conditions affecting bone density, and cannot be pregnant or refuse contraception if sexually active.

Inclusion Criteria

BMI between the 10th-85th percentiles

Availability of parent/guardian to provide informed consent

Expert clinical diagnosis of ASD confirmed using the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 Checklist and a Social Communication Questionnaire (SCQ)-Lifetime

Exclusion Criteria

I have a history of heart issues, including coronary disease or heart failure.

I have a genetic condition like Fragile X or tuberous sclerosis.

I have a condition that could cause low bone density.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive intranasal oxytocin or placebo for 12 months

12 months

Visits at baseline, week 2, and months 6, 12

Open-label extension

All participants receive intranasal oxytocin for 6 months

6 months

Visit at month 18

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Phone calls every two weeks for the first two months and monthly thereafter

Treatment Details

Interventions

• Intranasal oxytocin spray
• Intranasal Oxytocin spray
• Intranasal placebo spray

Trial Overview The study tests intranasal oxytocin's effects on bone health in autistic children versus a placebo. Participants will use the spray twice daily for a year, then all receive oxytocin for another six months. The trial includes regular visits and calls, physical exams, EKGs, lab tests for bone metabolism markers, diet/exercise questionnaires, and imaging of bones.

Participant Groups

Group I: 1. Intranasal Oxytocin Experimental Treatment 2 Interventions

Intranasal oxytocin spray (30 IU twice daily) for 12 months in the double-blinded phase followed by intranasal oxytocin spray (30 IU twice daily) for 6-months in the open-label phase

Group II: 2. Placebo Placebo Group 2 Interventions

Intranasal placebo spray (30 IU twice daily (total 60 IU per day) for 12 months followed by intranasal oxytocin spray (30 IU twice daily) for 6-months in the open-label phase

Intranasal oxytocin spray is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Pitocin for:

• Induction of labor
• Control of postpartum hemorrhage

Approved in European Union as Syntocinon for:

• Induction of labor
• Control of postpartum hemorrhage

Approved in Canada as oxytocin for:

• Induction of labor
• Control of postpartum hemorrhage

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Elizabeth Austen Lawson

Lead Sponsor

Trials

4

Recruited

200+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

University of Virginia

Collaborator

Trials

802

Recruited

1,342,000+

Findings from Research

A new formulation of intranasal oxytocin, TTA-121, showed an inverted U-shaped dose-response relationship for improving core symptoms of autism spectrum disorder, with the most effective dose being lower than previously expected at 6 U/day.

In a trial involving 109 adult males with high-functioning autism, TTA-121 significantly reduced the reciprocity score on the Autism Diagnostic Observation Schedule compared to placebo, particularly in the per protocol analysis, suggesting potential efficacy that warrants further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of a novel nasal oxytocin spray with enhanced bioavailability on autism: a randomized trial. Yamasue, H., Kojima, M., Kuwabara, H., et al.[2022]

A systematic review of five randomized controlled trials involving 223 participants found that long-term use of intranasal oxytocin in treating autism spectrum disorder (ASD) is generally well tolerated, with common side effects like nasal discomfort and tiredness not significantly linked to the treatment.

While some severe adverse events were reported, such as aggression and seizures, the overall safety profile suggests that intranasal oxytocin is safe for use in the ASD population, warranting further research to assess its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review and meta-analysis of reported adverse events of long-term intranasal oxytocin treatment for autism spectrum disorder. Cai, Q., Feng, L., Yap, KZ.[2018]

In a double-blind, placebo-controlled trial involving 50 male participants aged 12 to 18 with autism spectrum disorders, oxytocin nasal spray showed no significant improvement in social behavior compared to placebo after 8 weeks of treatment.

Despite the lack of clinical efficacy, caregivers who believed their children received oxytocin reported perceived improvements, suggesting that expectations may influence treatment outcomes; however, oxytocin was well tolerated with no increased side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of a course of intranasal oxytocin on social behaviors in youth diagnosed with autism spectrum disorders: a randomized controlled trial. Guastella, AJ., Gray, KM., Rinehart, NJ., et al.[2015]

In a 24-week placebo-controlled trial involving 290 children and adolescents with autism spectrum disorder, intranasal oxytocin therapy did not show significant improvements in social functioning compared to placebo, with a negligible difference in the primary outcome measure.

The safety profile of intranasal oxytocin was comparable to that of the placebo, as the incidence and severity of adverse events were similar between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder. Sikich, L., Kolevzon, A., King, BH., et al.[2022]

In a clinical trial involving 31 young children with autism, oxytocin nasal spray significantly improved social responsiveness compared to a placebo, suggesting its potential as an effective early intervention.

The treatment was well tolerated, with common side effects including thirst, urination, and constipation, indicating that oxytocin may be a safe option for improving social interactions in young children with autism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: a randomized clinical crossover trial. Yatawara, CJ., Einfeld, SL., Hickie, IB., et al.[2022]

Intranasal oxytocin has been studied in 261 children across various trials, primarily focusing on autism spectrum disorder (ASD) and Prader-Willi syndrome (PWS), but results for efficacy in ASD are mixed and there is currently no evidence supporting its benefit for PWS.

Adverse events related to intranasal oxytocin are mostly mild, with few moderate or severe cases reported, indicating a generally safe profile; however, monitoring and reporting of these events are inconsistent, highlighting the need for improved adherence and safety protocols in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of the Safety, Efficacy and Mechanisms of Delivery of Nasal Oxytocin in Children: Therapeutic Potential for Autism and Prader-Willi Syndrome, and Recommendations for Future Research. DeMayo, MM., Song, YJC., Hickie, IB., et al.[2018]

A study involving 95 generally healthy older men found that chronic intranasal oxytocin (OT) administration for 4 weeks was safe and well-tolerated, with no significant adverse effects on cardiovascular or metabolic health.

The incidence and severity of adverse events were low and similar between the OT and placebo groups, suggesting that OT does not increase the risk of side effects in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of chronic intranasal oxytocin in older men: results from a randomized controlled trial. Rung, JM., Horta, M., Tammi, EM., et al.[2023]

This study is the first double-blind randomized controlled trial examining the side effects of intranasal oxytocin in 100 elementary school-aged children, showing that it is likely safe with no significant side effects reported.

Most side effects were mild and resolved within 24 hours, indicating that intranasal oxytocin is well tolerated in children aged 8-12 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No side-effects of single intranasal oxytocin administration in middle childhood. Verhees, MWFT., Houben, J., Ceulemans, E., et al.[2019]

TTA-121, a new intranasal oxytocin formulation, delivers significantly more oxytocin to the brain compared to the standard Syntocinon formulation, with a 3.6-fold increase in brain concentration after administration in rabbits.

The study suggests that TTA-121 effectively targets brain areas associated with social behavior, potentially enhancing its therapeutic effects for autism spectrum disorder, as indicated by increased radioactivity in regions linked to pharmacological action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebral and extracerebral distribution of radioactivity associated with oxytocin in rabbits after intranasal administration: Comparison of TTA-121, a newly developed oxytocin formulation, with Syntocinon. Ishii, D., Kageyama, M., Umeda, S.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Effect of a novel nasal oxytocin spray with enhanced bioavailability on autism: a randomized trial. [2022]

2. Australia pubmed.ncbi.nlm.nih.gov

Systematic review and meta-analysis of reported adverse events of long-term intranasal oxytocin treatment for autism spectrum disorder. [2018]

3. England pubmed.ncbi.nlm.nih.gov

The effects of a course of intranasal oxytocin on social behaviors in youth diagnosed with autism spectrum disorders: a randomized controlled trial. [2015]

4. United States pubmed.ncbi.nlm.nih.gov

Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder. [2022]

5. England pubmed.ncbi.nlm.nih.gov

The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: a randomized clinical crossover trial. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

A Review of the Safety, Efficacy and Mechanisms of Delivery of Nasal Oxytocin in Children: Therapeutic Potential for Autism and Prader-Willi Syndrome, and Recommendations for Future Research. [2018]

7. Germany pubmed.ncbi.nlm.nih.gov

Safety and tolerability of chronic intranasal oxytocin in older men: results from a randomized controlled trial. [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

No side-effects of single intranasal oxytocin administration in middle childhood. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Cerebral and extracerebral distribution of radioactivity associated with oxytocin in rabbits after intranasal administration: Comparison of TTA-121, a newly developed oxytocin formulation, with Syntocinon. [2022]