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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a nasal spray containing oxytocin can improve bone health in children with autism. Oxytocin is a hormone that may positively affect bone density. Participants will receive either the intranasal oxytocin spray or a placebo (a non-active spray) for 12 months, followed by oxytocin for an additional 6 months. Children with an autism diagnosis, aged 6 to 18, and with a BMI above the 5th percentile may be suitable for this study. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant findings.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that oxytocin nasal spray is generally safe for people with autism. Studies indicate it is well-tolerated and does not cause major side effects. A detailed review found no link between oxytocin nasal spray and harmful effects, even in large clinical trials. These findings suggest it is likely safe for children and teenagers. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for autism?

Unlike the standard treatments for autism, which often include behavioral therapy and medications like antipsychotics and stimulants, the oxytocin nasal spray offers a novel approach by targeting social functioning directly through a hormone. Oxytocin is sometimes called the "love hormone" because it's linked to social bonding and trust, and researchers believe it might improve social interaction in people with autism. This treatment is delivered intranasally, making it non-invasive and easy to administer. Researchers are excited because this could provide a new, more direct way to address social challenges in autism, potentially offering improvements in social engagement and communication.

What evidence suggests that intranasal oxytocin might be an effective treatment for autism?

Research shows that a nasal spray with oxytocin, which participants in this trial may receive, might help children with autism who struggle with social skills. Studies have found that this treatment can enhance their interaction and communication with others. Some research also suggests it could similarly benefit teenagers with autism. However, its effect on repetitive behaviors remains unclear. Overall, while the results are promising, more studies are needed to fully understand how oxytocin can benefit people with autism. ^{1 2 4 6 7}

Who Is on the Research Team?

Elizabeth A Lawson, MD

Principal Investigator

Neuroendocrine Unit Massachusetts General Hospital

Are You a Good Fit for This Trial?

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

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

Availability of parent/guardian to provide informed consent

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6465037/

Intranasal oxytocin for autism spectrum disorders (ASD) - PMC To assess the efficacy of intranasal oxytocin in improving social interaction and communication deficit, and other clinical outcomes in autism spectrum ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2103583

Intranasal Oxytocin in Children and Adolescents with ... Experimental studies and small clinical trials have suggested that treatment with intranasal oxytocin may reduce social impairment in ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01908205

Intranasal Oxytocin for the Treatment of Children and ... In this context, we propose a randomized placebo controlled trial of intranasal oxytocin in children and adolescents with ASD. Official Title. Intranasal ...

4. nature.com nature.com/articles/s41467-023-44334-4

Chronic oxytocin administration stimulates the ... Clinical efficacy of intranasal administration of oxytocin is increasingly explored in autism spectrum disorder, but to date, the biological ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0306453024001112

The effects of oxytocin administration on social and ... Frequentist meta-analysis suggested oxytocin improves social outcomes in autism. •. Oxytocin's effect on routinized behavior outcomes was inconclusive. •.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0306453011000862

A review of safety, side-effects and subjective reactions to ... This paper reviewed side effects and safety data on the use of intranasal oxytocin in 38 controlled trials conducted over the last 20 years.

7. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/pcn.12627

Systematic review and meta‐analysis of reported adverse ... Results from this systematic review support intranasal oxytocin as well tolerated and safe for use in the ASD population. Larger clinical trials ...