Oxytocin Nasal Spray for Chronic Pain

Recruiting at 2 trial locations

Overseen By David Flusk

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Memorial University of Newfoundland

Must be taking: Pain management

Must not be taking: Nasal sprays

Disqualifiers: Pregnancy, Cancer, Severe depression, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 10 weeks

336 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

No, you won't have to stop taking your current medications. The trial requires that you have been on stable medication for pain management for at least 3 months and that there are no anticipated changes during the 10 weeks of the trial.

What evidence supports the effectiveness of the drug oxytocin nasal spray for chronic pain?

While there is no direct evidence for oxytocin nasal spray in chronic pain, studies on nasal sprays for pain relief, like fentanyl and butorphanol, show that nasal delivery can be effective for rapid pain relief. This suggests that nasal sprays, in general, might be a promising way to deliver pain-relieving drugs. ^{1 2 3 4 5}

How does the oxytocin nasal spray drug for chronic pain differ from other treatments?

The oxytocin nasal spray for chronic pain is unique because it uses oxytocin, a hormone often associated with social bonding, as a potential pain reliever, and it is administered through the nose, which is less common for pain treatments. This contrasts with other pain treatments like fentanyl, which is a strong opioid and can be delivered in various forms, including nasal sprays, but primarily targets opioid receptors for pain relief. ^{1 6 7 8 9}

What is the purpose of this trial?

One in five Canadians live with chronic pain, defined as pain that lasts longer than 3-months. Living with chronic pain has a detrimental impact on physical health, emotional health, and quality of life. Current treatments rarely result in pain relief and often do not meaningfully improve physical or emotional function. Further, medication used to treat pain often causes unwanted symptoms. There is a need to develop new treatments to help manage chronic pain. The use of a nasal spray containing manufactured oxytocin may improve pain management. Oxytocin is produced in the human body and has been shown to impact the pain pathway in animals. Our project tests whether the use of a nasal spray containing oxytocin will improve pain and function in men and women who live with chronic pain. Men and women with chronic nerve, muscle, or pelvic pain will be recruited in Vancouver, Calgary, and St. John's. Each person will be assigned to complete three interventions in a random order. Each intervention involves using a nasal spray twice per day over a 2-week period. The nasal spray will contain a small dose of oxytocin during one intervention and a medium dose during the second intervention. The nasal spray during the final intervention will have no oxytocin. This final intervention is a control intervention that will allow us to measure the effect of simply taking a nasal spray (i.e., the impact of expectation). Participants and researchers will not know which interventions involve the use of oxytocin. Participants will rate their pain and function each day throughout each task. The investigators will calculate each person's score on pain and function. The investigators will test whether participants report less pain and better function when they use oxytocin compared to the control. The results of this project may improve pain, function, and quality of life among those who live with chronic pain.

Research Team

Joshua Rash, PhD

Principal Investigator

Memorial University of Newfoundland

Eligibility Criteria

Adult men and premenopausal women with chronic pain in muscles, nerves, or the pelvic region can join this trial. They must have moderate pain levels and be on stable pain medication for at least 3 months. Participants should not be pregnant, planning pregnancy, or have significant depression or certain medical conditions like heart issues or nasal pathology.

Inclusion Criteria

My pain level is moderate, between 4 and 8 on a scale of 10.

I have been on a stable pain medication plan for 3+ months with no changes expected.

I have primary pain in my back, neck, or shoulder.

Exclusion Criteria

I have diabetes insipidus.

You are allergic to oxytocin.

I have or had cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo three 2-week interventions using intranasal oxytocin or placebo, with a 2-week wash-out period between each intervention

10 weeks

Daily self-administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• 24-IU oxytocin
• 48-IU oxytocin
• Placebo

Trial Overview The study tests if a nasal spray containing oxytocin can improve chronic pain management compared to a placebo. Participants will use two different doses of oxytocin sprays and one placebo spray across three sessions without knowing which they're receiving. Their daily pain and function ratings will help determine the effectiveness of oxytocin.

Participant Groups

Group I: Crossover sequence 2: placebo first Experimental Treatment 3 Interventions

Patients receive 2-weeks courses of placebo, 24-IU oxytocin, 48-IU oxytocin.

Group II: Crossover sequence 1: Oxytocin first Experimental Treatment 3 Interventions

Patients receive 2-weeks courses of 24-IU oxytocin, placebo, 48-IU oxytocin.

Who Is Running the Clinical Trial?

Memorial University of Newfoundland

Lead Sponsor

Trials

73

Recruited

1,836,000+

University of British Columbia

Collaborator

Trials

1,506

Recruited

2,528,000+

University of Calgary

Collaborator

Trials

827

Recruited

902,000+

Findings from Research

In a pilot study involving 24 gynecological patients, nasal fentanyl spray provided rapid and effective postoperative pain relief comparable to intravenous fentanyl, with analgesia onset within 5 minutes.

Both formulations of nasal fentanyl were generally well-tolerated, with no significant differences in side effects compared to intravenous administration, although a majority of patients still preferred the intravenous route.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new formulation of nasal fentanyl spray for postoperative analgesia: a pilot study. Paech, MJ., Lim, CB., Banks, SL., et al.[2019]

Transnasal butorphanol (TB) significantly improved pain relief measures, such as the visual analogue scale (VAS) and Clinical Global Impression scores, in patients after uvulopalatopharyngoplasty (UPPP) for obstructive sleep apnea, indicating its efficacy for postoperative pain management.

The study demonstrated that TB is safe for use in patients undergoing oropharyngeal surgery, with no major complications reported during the trial involving 12 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transnasal butorphanol for pain relief after uvulopalatopharyngoplasty - a hospital-based,randomized study. Huang, HC., Lee, LA., Fang, TJ., et al.[2013]

A study involving 108 patients with severe postepisiotomy pain found that both 25 mg and 50 mg doses of ketoprofen were effective in providing pain relief, showing similar efficacy to 500 mg of dipyrone.

All active treatments significantly outperformed placebo, with over 75% of patients in the active groups rating their pain relief as 'good' or 'excellent', and no adverse events were reported, indicating a good safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analgesic efficacy of liquid ketoprofen compared to liquid dipyrone and placebo administered orally as drops in postepisiotomy pain. Olson, NZ., Sunshine, A., Zighelboim, I., et al.[2015]

Intranasal fentanyl spray (INFS) provided significantly faster 'meaningful' pain relief for cancer-related breakthrough pain compared to oral transmucosal fentanyl citrate (OTFC), with a median onset time of 11 minutes for INFS versus 16 minutes for OTFC.

Patients preferred INFS over OTFC due to its ease of use and effectiveness, achieving greater pain intensity reductions at earlier time points, while both treatments were well tolerated with nausea being the most common side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of intranasal fentanyl spray with oral transmucosal fentanyl citrate for the treatment of breakthrough cancer pain: an open-label, randomised, crossover trial. Mercadante, S., Radbruch, L., Davies, A., et al.[2014]

Intranasal fentanyl is rapidly absorbed and offers a promising method for pain management, particularly for breakthrough pain in cancer patients, with advantages over oral forms such as faster onset and easier administration.

New formulations of fentanyl nasal sprays, like PecFent and Instanyl, are designed to minimize runoff and improve absorption, making them more effective while also requiring lower volumes for effective dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nasal delivery of fentanyl. Watts, P., Smith, A., Perelman, M.[2018]

Using Merocele nasal packs soaked with levobupivacaine significantly reduced postoperative pain levels in patients after septoplasty compared to saline-soaked packs, as measured by visual analogue scale (VAS) scores at multiple time points up to 12 hours post-surgery.

Patients receiving levobupivacaine required less supplemental analgesia, indicating that this method not only alleviates pain effectively but also enhances overall patient comfort after the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of topical levobupivacaine in control of postoperative pain after septoplasty. Yilmaz, S., Kocaman Akbay, B., Yildizbaş, S., et al.[2018]

The FDA has approved a new nasal spray formulation of fentanyl, called Lazanda-Archimedes, specifically for managing breakthrough pain in adult cancer patients who are already tolerant to opioid therapy.

This approval adds to the existing forms of fentanyl available in the US, which include intravenous, intrathecal, epidural, transdermal, and oral transmucosal options, providing more flexibility in pain management for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fentanyl nasal spray (Lazanda) for pain. [2013]

Intranasal ketorolac has been shown to significantly reduce pain in adult patients, with one phase III study reporting a mean pain intensity difference score of 83.3 compared to 37.2 for placebo, indicating its efficacy as a non-opioid analgesic.

The drug is well-tolerated, with most adverse events related to the administration route, and it has a rapid absorption time of 0.50-0.75 hours, making it a viable option for short-term pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of intranasal ketorolac tromethamine for the short-term management of moderate to moderately severe pain that requires analgesia at the opioid level. He, A., Hersh, EV.[2013]

Fentanyl-TTS (transdermal system) effectively manages postoperative pain, providing continuous analgesic release for 72 hours, although patients may require additional analgesics during the first 12 hours due to a lag in effect.

While fentanyl-TTS shows efficacy, it carries a risk of respiratory depression in up to 9% of patients, along with other side effects like nausea (62%) and local skin reactions (39%), highlighting the need for careful monitoring during use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Fentanyl-TTS for postoperative pain therapy. A new alternative?]. Donner, B., Zenz, M., Tryba, M., et al.[2013]

References

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

A new formulation of nasal fentanyl spray for postoperative analgesia: a pilot study. [2019]

2. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

Transnasal butorphanol for pain relief after uvulopalatopharyngoplasty - a hospital-based,randomized study. [2013]

3. Germany pubmed.ncbi.nlm.nih.gov

Analgesic efficacy of liquid ketoprofen compared to liquid dipyrone and placebo administered orally as drops in postepisiotomy pain. [2015]

4. England pubmed.ncbi.nlm.nih.gov

A comparison of intranasal fentanyl spray with oral transmucosal fentanyl citrate for the treatment of breakthrough cancer pain: an open-label, randomised, crossover trial. [2014]

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

Nasal delivery of fentanyl. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Efficacy of topical levobupivacaine in control of postoperative pain after septoplasty. [2018]

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

Fentanyl nasal spray (Lazanda) for pain. [2013]

8. England pubmed.ncbi.nlm.nih.gov

A review of intranasal ketorolac tromethamine for the short-term management of moderate to moderately severe pain that requires analgesia at the opioid level. [2013]

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

[Fentanyl-TTS for postoperative pain therapy. A new alternative?]. [2013]