Intranasal Oxytocin for Caregiver Stress

Overseen By Minjoo Kang, MEd

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Nebraska

Must not be taking: Antipsychotics, SSRIs, Corticosteroids

Disqualifiers: Severe liver disease, Seizure disorder, CNS disease, others

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

Compensation: Varies

Number of Visits: 3

Duration: 3 weeks

32 Participants Needed

Trial Summary

What is the purpose of this trial?

The overall aim of this study is to determine the efficacy and safety of intranasal oxytocin (OXT) to improve the quality of life and reduce chronic stress levels in the caregivers to the persons with dementia. Randomized, double-blind, placebo-controlled clinical trial of intranasal oxytocin (12 or 24 IU) will be conducted by daily administration (once a day) for 21 days (3 weeks).

Will I have to stop taking my current medications?

If you are currently taking antipsychotic medications, selective serotonin reuptake inhibitors (SSRIs), or corticosteroid creams/pills, you will need to stop taking them to participate in this trial.

What data supports the effectiveness of the drug intranasal oxytocin for caregiver stress?

Research shows that intranasal oxytocin can increase oxytocin levels in the brain, which is linked to stress relief and improved social behaviors. In older adults, a 10-day trial of intranasal oxytocin improved feelings of gratitude and reduced fatigue, suggesting potential benefits for stress management. ^{1 2 3 4 5}

Is intranasal oxytocin safe for humans?

Intranasal oxytocin has been studied in various groups, including older men, children, and individuals with autism, and is generally considered safe with mild side effects like nasal discomfort and tiredness. Severe side effects are rare, and studies suggest it is well-tolerated in both adults and children. ^{3 6 7 8 9}

How is the drug intranasal oxytocin unique for treating caregiver stress?

Intranasal oxytocin is unique because it is delivered through the nose, allowing it to reach the brain more effectively than other methods, and it specifically targets stress relief by reducing cortisol levels, a stress hormone, during stressful situations. ^{2 3 10 11 12}

Research Team

Soonjo Hwang, MD

Principal Investigator

University of Nebraska

Eligibility Criteria

This trial is for caregivers of individuals with dementia. Participants should be in good general health and able to undergo an MRI scan. Specific details about who can join are not provided, but typically there would be age limits and other health requirements.

Inclusion Criteria

Right-handed

I am a woman aged 50 or older.

Capacity to read and write in English

Exclusion Criteria

Metal in the body (i.e., hearing aid, cardiac pacemaker, bone plates, braces, non-removable piercing/implants, etc.), claustrophobia, or any other condition that would preclude MRI scanning

Mini-mental status exam score of 25 or lower which suggests possible cognitive issues

History of or current drug or alcohol abuse

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 daily for 21 days

3 weeks

Daily administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Intranasal Oxytocin

Trial Overview The study tests if a nasal spray containing oxytocin (at two different doses: 12IU or 24IU) can improve life quality and reduce stress compared to a placebo. It's double-blind, meaning neither the researchers nor participants know who gets oxytocin or placebo.

Participant Groups

Group I: Oxytocin Intranasal Spray 12 International Unit (IU) Active Control 2 Interventions

Nasal spray of Oxytocin 12 International Unit (12IU) liquid solution as 2 puffs of daily dose (every morning) for 3 weeks. Functional magnetic resonance imaging (fMRI) scan pre- and post-administration.

Group II: Oxytocin Intranasal Spray 24 International Unit (IU) Active Control 2 Interventions

Nasal spray of Oxytocin 24 International Unit (12IU) liquid solution as 2 puffs of daily dose (every morning) for 3 weeks. Functional magnetic resonance imaging (fMRI) scan pre- and post-administration.

Group III: Intranasal Spray Placebo Placebo Group 2 Interventions

Nasal Spray of placebo liquid solution as 2 puffs of daily dose (every morning) for 3 weeks. Functional magnetic resonance imaging (fMRI) scan pre- and post-administration.

Who Is Running the Clinical Trial?

University of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

Findings from Research

Oxytocin (OXT) can be effectively delivered to the brain through nasal administration, achieving higher brain concentrations compared to intravenous delivery, despite lower plasma levels.

The study found that the nasal bioavailability of OXT is approximately 2%, and its therapeutic effects, such as stress relief, were observed only after intranasal application, highlighting the potential of this route for treating conditions like autism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delivery of Oxytocin to the Brain for the Treatment of Autism Spectrum Disorder by Nasal Application. Tanaka, A., Furubayashi, T., Arai, M., et al.[2019]

Intranasal administration of oxytocin (OT) effectively increases its concentration in the cerebrospinal fluid (CSF) and plasma, suggesting it can reach central nervous system targets.

Both delivery methods (intranasal spray and nebulizer) were effective in elevating CSF OT levels, with the nasal spray showing greater increases in plasma OT concentration compared to the nebulizer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CSF and blood oxytocin concentration changes following intranasal delivery in macaque. Dal Monte, O., Noble, PL., Turchi, J., et al.[2021]

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]

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]

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]

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]

References

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

Short communication: pharmacokinetics of oxytocin administered intranasally to beef cattle. [2021]

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

Delivery of Oxytocin to the Brain for the Treatment of Autism Spectrum Disorder by Nasal Application. [2019]

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

Oxytocin interference in the effects induced by inhalation of 7.5% CO(2) in healthy volunteers. [2013]

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

Effects of a 10-day oxytocin trial in older adults on health and well-being. [2013]

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

CSF and blood oxytocin concentration changes following intranasal delivery in macaque. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

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

7. 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]

8. 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]

9. Germany pubmed.ncbi.nlm.nih.gov

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

10. England pubmed.ncbi.nlm.nih.gov

Evidence for intranasal oxytocin delivery to the brain: recent advances and future perspectives. [2019]

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

Coping style moderates the effect of intranasal oxytocin on the mood response to interpersonal stress. [2018]

12. England pubmed.ncbi.nlm.nih.gov

Intranasal oxytocin attenuates the cortisol response to physical stress: a dose-response study. [2013]