Oxytocin for Chronic Pain

Overseen By Regina Curry, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Wake Forest University Health Sciences

Must not be taking: Benzodiazepines, Pain medications

Disqualifiers: Neuropathy, Chronic pain, Diabetes, 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: 2

Duration: 1 day per visit, with visits separated by at least 48 hours

38 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how oxytocin, a naturally occurring hormone, might help manage chronic pain by affecting the parasympathetic nervous system. The parasympathetic nervous system helps the body relax and conserve energy, potentially aiding in pain relief. Participants will receive an injection of either oxytocin or a placebo to compare effects. Individuals with knee arthritis, well-managed blood pressure, and not on daily pain medication might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that participants do not take benzodiazepines or pain medications daily. If you are on these medications, you would need to stop taking them to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that oxytocin, a hormone naturally found in the body, is under study for its effects on pain relief. The results are mixed regarding its effectiveness in reducing pain, but researchers are testing it for potential benefits.

Regarding safety, oxytocin is already used in hospitals, often to assist with childbirth. This provides some understanding of its effects and possible risks. For instance, it can cause uterine contractions, which are important during labor but not a concern for those who are not pregnant.

In this trial, oxytocin is administered as an injection into the muscle. Past studies and medical use suggest that this method is generally safe. However, like any treatment, some individuals might experience side effects.

Although specific information about side effects from available studies is limited, the fact that oxytocin is already approved for other uses suggests it might be well-tolerated. Participants in this trial will be closely monitored for any side effects to ensure safety. ^{1 2 3 4 5}

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

Most treatments for chronic pain, like NSAIDs and opioids, work by reducing inflammation or blocking pain signals. But oxytocin works differently, targeting social and emotional pathways in the brain to potentially enhance mood and reduce pain perception. This hormone, often associated with affection and bonding, offers a novel approach as it might help manage pain with fewer side effects. Researchers are excited about oxytocin because it could offer a safer, more holistic way to address chronic pain, especially for those who don't respond well to conventional therapies.

What evidence suggests that this trial's treatments could be effective for chronic pain?

Research suggests that oxytocin, one of the treatments under study in this trial, might help reduce chronic pain. Some studies have shown that oxytocin can lower pain for individuals with back and abdominal pain. However, a review of other studies found that oxytocin did not significantly lessen pain. Despite these mixed results, additional research indicates oxytocin could improve pain and quality of life for those with chronic pain. Overall, there is some promising evidence, but results have varied. Participants in this trial will receive either oxytocin or a placebo in different sequences to further investigate its effects. ^{1 2 3 5 6}

Who Is on the Research Team?

James C Eisenach, MD

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with good health, normal blood pressure or controlled hypertension, and a BMI under 40. It's open to both healthy volunteers and those with knee arthritis. Women of childbearing age must use effective birth control. People can't join if they have certain health risks, are pregnant/nursing/recently pregnant, suffer from chronic pain or diabetes, take daily benzodiazepines/pain meds, or have specific eye conditions.

Inclusion Criteria

My blood pressure and heart rate are within the normal range without medication.

My blood pressure is normal or controlled, and my heart rate is between 45-100 bpm.

I am using effective birth control or abstaining from sex.

Exclusion Criteria

You have had a strong allergic reaction to any ingredient in Pitocin®.

I have neuropathy, chronic pain, diabetes, or take daily pain medication.

I have eye conditions or have had eye surgery that affects my vision or causes tremors.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an intramuscular injection of placebo or oxytocin, with pupil diameter measured every 2.5 minutes for 180 minutes

1 day per visit, with visits separated by at least 48 hours

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Oxytocin
• Placebo

Trial Overview The study tests the impact of oxytocin (a hormone) given by muscle injection on the 'rest and digest' nervous system activity through pupil response in people with chronic pain/osteoarthritis versus a placebo.

How Is the Trial Designed?

Group I: Placebo, Then Oxytocin Experimental Treatment 2 Interventions

Subjects in this arm will receive Intramuscular placebo injection first then oxytocin injection

Group II: Oxytocin First, then Placebo Experimental Treatment 2 Interventions

Subjects in this arm will receive Intramuscular injection of Oxytocin (Pitocin®) first then placebo injection.

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

Approved in United States as Pitocin for:

• Induction of labor
• Augmentation of labor
• Control of postpartum bleeding

Approved in European Union as Syntocinon for:

• Induction of labor
• Augmentation of labor
• Control of postpartum bleeding

Approved in Canada as Oxytocin for:

• Induction of labor
• Augmentation of labor
• Control of postpartum bleeding

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

In a study involving 25 male volunteers, the oxytocin analogue carbetocin demonstrated significant anti-nociceptive effects, reducing pain sensitivity in response to electrical stimuli and decreasing the area of capsaicin-induced allodynia.

Carbetocin was shown to effectively increase pain thresholds and reduce pain responses, suggesting its potential as a therapeutic option for managing pain in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-nociceptive effects of oxytocin receptor modulation in healthy volunteers-A randomized, double-blinded, placebo-controlled study. Biurrun Manresa, JA., Schliessbach, J., Vuilleumier, PH., et al.[2021]

Oxytocin, a neuropeptide hormone, shows promise as a potential treatment for chronic pain due to its role in modulating both psychological and physiological processes related to pain.

Current research indicates that oxytocin may effectively alter the pain experience, but more studies are needed to fully understand its mechanisms and therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxytocin and the modulation of pain experience: Implications for chronic pain management. Tracy, LM., Georgiou-Karistianis, N., Gibson, SJ., et al.[2015]

Oxytocin analogues have been developed that are more stable and can effectively penetrate the brain, showing strong potential as non-addictive alternatives for pain relief compared to traditional opioids.

These new oxytocin analogues demonstrate potent pain relief in mice, suggesting they could be a promising option for treating acute and chronic pain while avoiding the negative side effects associated with opioids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Structure-Based Design of Glycosylated Oxytocin Analogues with Improved Selectivity and Antinociceptive Activity. Szabó, LZ., Tanguturi, P., Goodman, HJ., et al.[2023]

This trial aims to evaluate the efficacy of intranasal oxytocin as a non-addictive treatment for chronic pain, involving adults with various pain conditions across three Canadian provinces, using a placebo-controlled, triple-blind design.

Participants will self-administer different doses of oxytocin nasal spray over two weeks, with primary outcomes focused on pain relief and secondary outcomes including emotional function and sleep disturbance, providing a comprehensive assessment of oxytocin's potential analgesic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the efficacy of intranasal oxytocin on pain and function among individuals who experience chronic pain: a protocol for a multisite, placebo-controlled, blinded, sequential, within-subjects crossover trial. Rash, JA., Campbell, TS., Cooper, L., 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]

This trial will evaluate the efficacy of intranasal oxytocin in improving pain and function in 50 women with chronic pelvic musculoskeletal pain, focusing on its potential to decrease pain sensitivity due to the presence of oxytocin receptors in the uterus.

The study is designed as a double-blind, placebo-controlled crossover trial, which will assess the safety and side effects of oxytocin over a 14-day period, providing valuable insights into its use as an adjuvant treatment for chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol for a placebo-controlled, within-participants crossover trial evaluating the efficacy of intranasal oxytocin to improve pain and function among women with chronic pelvic musculoskeletal pain. Rash, JA., Toivonen, K., Robert, M., et al.[2022]

In a study involving 21 women with chronic pelvic pain, intranasal oxytocin showed a significant reduction in pain severity compared to placebo, with about one in three women experiencing a clinically meaningful improvement.

The treatment was well-tolerated, with no significant difference in adverse effects between oxytocin and placebo, suggesting it could be a safe adjuvant option for managing chronic pelvic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal oxytocin as a treatment for chronic pelvic pain: A randomized controlled feasibility study. Flynn, MJ., Campbell, TS., Robert, M., et al.[2021]

Chronic pain is a significant issue that not only affects physical health but also mental well-being, often leading to anxiety and depression, and poses an economic burden due to the need for ongoing medical treatment.

Preliminary evidence suggests that oxytocin may be a promising candidate for pain relief, potentially offering a safer and more effective alternative to traditional analgesics like opioids and NSAIDs, which have serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The analgesic effects of oxytocin in the peripheral and central nervous system. Xin, Q., Bai, B., Liu, W.[2022]

LIT-001, a non-peptide full agonist of the oxytocin receptor, shows promise in reducing inflammatory pain in a rat model, indicating its potential as a new pain treatment option.

Unlike oxytocin, which has a very short half-life and poor absorption, LIT-001 offers a longer-lasting analgesic effect, suggesting it could overcome some of the limitations of traditional oxytocin use in pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Nonpeptide Oxytocin Receptor Agonist for a Durable Relief of Inflammatory Pain. Hilfiger, L., Zhao, Q., Kerspern, D., et al.[2023]

Positive verbal suggestions significantly enhanced expectations of pain relief and induced placebo analgesia in 108 female participants, demonstrating that the way treatment is communicated can influence outcomes.

Oxytocin administration did not enhance the placebo effect or expectations for pain or itch relief, suggesting that while verbal suggestions are effective, oxytocin may not play a role in boosting placebo responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancing Placebo Effects in Somatic Symptoms Through Oxytocin. Skvortsova, A., Veldhuijzen, DS., Van Middendorp, H., et al.[2019]

Citations

1. mdpi.com mdpi.com/2075-1729/14/2/253

Oxytocin Modulation in Mindfulness-Based Pain ... Following Mindfulness-Based Pain Management, oxytocin levels significantly increased in chronic pain patients, that was not observed in the patient wait-list ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10187080/

Evaluating the efficacy of oxytocin for pain management Meta-analysis of three studies indicated that exogenous oxytocin administration did not result in a significant reduction in pain intensity ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4276444/

Oxytocin – A Multifunctional Analgesic for Chronic Deep ... The present article reviews the existent human and basic science data related to the direct and indirect effects of oxytocin on pain.

4. tandfonline.com tandfonline.com/doi/abs/10.1080/24740527.2023.2191114

Evaluating the efficacy of oxytocin for pain management Narrative review provided encouraging evidence that exogenous oxytocin administration reduced pain sensitivity among individuals with back pain, abdominal pain, ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04903002

Evaluating the Efficacy of Intranasal Oxytocin on Chronic ... The results of this project may improve pain, function, and quality of life among those who live with chronic pain.

6. mayoclinic.org mayoclinic.org/drugs-supplements/oxytocin-intravenous-route-intramuscular-route/description/drg-20065254

Oxytocin (intravenous route, intramuscular route) Oxytocin can be very useful for helping labor. However, there are certain risks with using it. Oxytocin causes contractions of the uterus. In ...