Intranasal Oxytocin for Central Diabetes Insipidus

Overseen By Elizabeth A Lawson, MD, MMSc

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Elizabeth Austen Lawson

Must be taking: Hormone replacement

Disqualifiers: Substance use, Psychosis, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 3 visits

30 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial requires that there be no medication changes within 4 weeks before joining or during the study, so you may need to stop or adjust your current medications before enrolling.

What data supports the effectiveness of the drug oxytocin nasal spray for central diabetes insipidus?

Research on Brattleboro rats with diabetes insipidus shows that oxytocin can reduce symptoms by acting on the kidneys, suggesting it might help in managing diabetes insipidus in humans as well. ^{1 2 3 4 5}

Is intranasal oxytocin safe for use in humans?

Intranasal oxytocin has been studied in various populations, including children and adults, 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, though more research is needed to confirm its safety across different conditions. ^{4 6 7 8 9}

How does the drug oxytocin nasal spray differ from other treatments for central diabetes insipidus?

Oxytocin nasal spray is unique because it acts as a weak agonist of vasopressin, providing antidiuretic effects by influencing the kidneys, which is different from the more commonly used desmopressin that directly mimics the antidiuretic hormone. Additionally, oxytocin is administered intranasally, similar to some forms of desmopressin, but it offers a novel approach by utilizing oxytocin's properties. ^{2 3 10 11 12}

What is the purpose of this trial?

This is a randomized, double-blind, placebo-controlled crossover pilot study of single-dose intranasal oxytocin (4 IU and 24 IU) in 18-60-year-old men and women with central diabetes insipidus to evaluate the effect of oxytocin on anxiety, depression and socioemotional functioning. Following a screening visit to determine eligibility, participants will return for three main study visits. During the main study visits, study participants will receive either oxytocin or placebo, followed by assessments of emotional behavior. Thirty participants will be equally randomized to one of six possible drug orders: 1. 4 IU oxytocin - 24 IU oxytocin - placebo 2. 4 IU oxytocin - placebo - 24 IU oxytocin 3. 24 IU oxytocin - 4 IU oxytocin - placebo 4. 24 IU oxytocin - placebo - 4 IU oxytocin 5. placebo - 4 IU oxytocin - 24 IU oxytocin 6. placebo - 24 IU oxytocin - 4 IU oxytocin

Research Team

Elizabeth A Lawson, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for men and women aged 18-60 with central diabetes insipidus who have had stable hormone replacement therapy without dose changes for six weeks. Participants must not be pregnant, breastfeeding, or have a history of psychosis or substance abuse recently. They should also not be on any investigational drugs or have significant illnesses that could affect the study.

Inclusion Criteria

I have been diagnosed with central diabetes insipidus.

Your thyroid hormone levels are within the normal range.

My hormone replacement dose has been stable for the last six weeks.

Exclusion Criteria

Any significant illness or condition that the Investigator determines could interfere with study participation, data collection, or safety

You have a history of severe mental illness that includes losing touch with reality.

Pregnancy or breastfeeding within the last 8 weeks

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive intranasal oxytocin or placebo during three main study visits, followed by assessments of emotional behavior

3 visits

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Oxytocin nasal spray

Trial Overview The trial tests how intranasal oxytocin (4 IU and 24 IU doses) affects anxiety, depression, and socioemotional functioning in patients with central diabetes insipidus. It's randomized and double-blind, meaning neither researchers nor participants know who gets the real treatment versus placebo during the study.

Participant Groups

Group I: Placebo - 4 IU oxytocin - 24 IU oxytocin Experimental Treatment 1 Intervention

Main visit 1: intranasal placebo; Main visit 2: 4 IU intranasal oxytocin; Main visit 3: 24 IU intranasal oxytocin

Group II: Placebo - 24 IU oxytocin - 4 IU oxytocin Experimental Treatment 1 Intervention

Main visit 1: intranasal placebo; Main visit 2: 24 IU intranasal oxytocin; Main visit 3: 4 IU intranasal oxytocin

Group III: 4 IU oxytocin - placebo - 24 IU oxytocin Experimental Treatment 1 Intervention

Main visit 1: 4 IU intranasal oxytocin; Main visit 2: intranasal placebo; Main visit 3: 24 IU intranasal oxytocin

Group IV: 4 IU oxytocin - 24 IU oxytocin - placebo Experimental Treatment 1 Intervention

Main visit 1: 4 IU intranasal oxytocin; Main visit 2: 24 IU intranasal oxytocin; Main visit 3: intranasal placebo

Group V: 24 IU oxytocin - placebo - 4 IU oxytocin Experimental Treatment 1 Intervention

Main visit 1: 24 IU intranasal oxytocin; Main visit 2: intranasal placebo; Main visit 3: 4 IU intranasal oxytocin

Group VI: 24 IU oxytocin - 4 IU oxytocin - placebo Experimental Treatment 1 Intervention

Main visit 1: 24 IU intranasal oxytocin; Main visit 2: 4 IU intranasal oxytocin; Main visit 3: intranasal placebo

Oxytocin nasal spray is already approved in United States, European Union for the following indications:

Approved in United States as Pitocin for:

• Induction of labor
• Stimulation of uterine contractions

Approved in European Union as Syntocinon for:

• Induction of labor
• Stimulation of uterine contractions

Who Is Running the Clinical Trial?

Elizabeth Austen Lawson

Lead Sponsor

Trials

4

Recruited

200+

Findings from Research

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]

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]

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]

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]

Syntocinon(R), a synthetic form of oxytocin, was found to be as effective as natural oxytocin in a study involving 3,342 obstetrical patients.

The use of Syntocinon(R) showed no significant side effects, such as vasospasm or anaphylactic reactions, suggesting it is safe for clinical use in obstetrics when properly indicated and monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthetic oxytocin. HIBBARD, LT., ANDREWS, AV.[2018]

References

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

DIABETES INSIPIDUS. TREATMENT WITH 8-LYSINE VASOPRESSIN IN A NASAL SPRAY. [2018]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Antidiuretic effects of oxytocin in the Brattleboro rat. [2019]

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

Neurogenic diabetes insipidus: management with dDAVP (1-desamino-8-D arginine vasopressin). [2019]

4. Germany pubmed.ncbi.nlm.nih.gov

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

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

Oxytocin and cardioprotection in diabetes and obesity. [2018]

6. 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]

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

Synthetic oxytocin. [2018]

10. Japan pubmed.ncbi.nlm.nih.gov

Comparison of incidence of hyponatremia between intranasal and oral desmopressin in patients with central diabetes insipidus. [2015]

11. Australia pubmed.ncbi.nlm.nih.gov

Diabetes insipidus treated by DDAVP. [2021]

12. Italy pubmed.ncbi.nlm.nih.gov

[Effectiveness of and tolerability to oral desmopressin in the treatment of central diabetes insipidus]. [2013]