Oxytocin for Knee Osteoarthritis

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, SSRIs, MAOIs

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the hormone oxytocin can reduce pain in people with severe knee arthritis. Participants will receive oxytocin through an IV and then undergo a gentle heat test on their skin to measure pain relief. The study aims to determine if oxytocin can relieve pain for arthritis sufferers. Participants should be healthy volunteers or have knee arthritis severe enough to consider joint replacement. As a Phase 2 trial, this research measures oxytocin's effectiveness in an initial, smaller group, offering participants a chance to contribute to potential advancements in arthritis pain management.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you take certain medications daily, like benzodiazepines or pain medications, or if you are on specific drugs like thiazide diuretics, SSRIs, or MAOIs.

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

Research has shown that oxytocin, a hormone naturally found in the body, has been tested for safety in treating conditions like knee osteoarthritis. Studies, particularly those involving older adults, indicate that oxytocin is generally well-tolerated. In some trials, participants used oxytocin as a nasal spray for a month and reported no major safety issues.

The FDA has approved oxytocin for other uses, such as assisting with childbirth, suggesting it is relatively safe for humans. However, it's important to remember that everyone’s body can react differently. While the hormone is considered safe, some people might experience mild side effects like headaches or nausea. These side effects are uncommon but worth mentioning.

Overall, research suggests that oxytocin is a safe option. However, as with any treatment, joining a trial carries a small chance of unexpected effects. Discussing any concerns with the medical team running the trial is always a good idea. ^{1 2 3 4 5}

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

Unlike the standard treatments for knee osteoarthritis, like NSAIDs or corticosteroid injections, oxytocin is being explored for its potential to alleviate pain through a novel mechanism. Oxytocin, often known as the "love hormone," is primarily recognized for its role in social bonding, but researchers are intrigued by its potential anti-inflammatory and pain-relieving properties. This treatment could offer a new pathway for managing pain without the side effects associated with long-term use of current medications.

What evidence suggests that oxytocin might be an effective treatment for knee osteoarthritis?

Research suggests that oxytocin, the treatment under study in this trial, might help alleviate knee osteoarthritis pain. Studies on rats have shown that oxytocin can maintain bone strength and prevent breakdown, benefiting joint health. Other research has indicated that oxytocin could reduce pain in older adults with knee osteoarthritis. This hormone, naturally produced in the brain, is believed to aid pain relief by altering the body's pain perception. Although more human studies are needed, these early findings suggest oxytocin could be a useful treatment for managing osteoarthritis pain. ^{3 6 7 8 9}

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 a BMI under 40, either healthy or suffering from severe knee arthritis. Healthy participants must have normal blood pressure and heart rate without medication; those with arthritis can be on blood pressure meds. Women of childbearing age should use effective birth control.

Inclusion Criteria

Generally in good health as determined by the Principal Investigator based on prior medical history, American Society of Anesthesiologists physical status 1, 2, or 3

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.

Exclusion Criteria

Hypersensitivity, allergy, or significant reaction to any ingredient of Pitocin®

I felt little to no pain when my lower calf was heated up to 47°C.

I have a history of heart rhythm problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Participants receive an intravenous infusion of oxytocin for 30 minutes

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pain assessment 65 minutes after infusion

1 day

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Oxytocin

Trial Overview

The study tests the pain-reducing effects of oxytocin, given through an IV, in response to sustained heat applied to the skin. Participants will rate their pain during this process to help develop a model for peripheral analgesia using oxytocin.

How Is the Trial Designed?

Group I: Verbal pain score at 7 minutes Experimental Treatment 1 Intervention

Verbal pain score is recorded at the end of 5 minutes of heating the skin. In this arm the first score is obtained at 7 minutes after starting the intervention, then every 15 minutes for 60 minutes

Group II: Verbal pain score at 5 minutes Experimental Treatment 1 Intervention

Verbal pain score is recorded at the end of 5 minutes of heating the skin. In this arm the first score is obtained at 5 minutes after starting the intervention, then every 15 minutes for 60 minutes

Group III: Verbal pain score at 2 minutes Experimental Treatment 1 Intervention

Verbal pain score is recorded at the end of 5 minutes of heating the skin. In this arm the first score is obtained at 2 minutes after starting the intervention, then every 15 minutes for 60 minutes

Group IV: Verbal pain score at 10 minutes Experimental Treatment 1 Intervention

Verbal pain score is recorded at the end of 5 minutes of heating the skin. In this arm the first score is obtained at 10 minutes after starting the intervention, then every 15 minutes for 60 minutes

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+

Published Research Related to This Trial

Oxytocin is widely used to augment labor in low-risk first-time mothers, with a survey indicating that 38% of such labors in the UK are treated with intravenous syntocinon.

There is significant variation in the dosing and administration of syntocinon across Scottish obstetric units, which raises concerns about potential risks to both mothers and fetuses due to misuse, highlighting the need for standardized guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variations in oxytocin regimes in Scottish labour wards in 1998. Arnott, N., Harrold, AJ., Lynch, P.[2004]

In a study involving ovariectomized (OVX) rats, oxytocin (OT) treatment for eight weeks helped maintain bone mass density (BMD) and prevented bone degeneration compared to OVX rats without treatment.

The results showed that OVX rats treated with OT had similar bone health markers, including osteocyte and osteoblast numbers, to sham-operated rats, suggesting that OT may have a protective antiosteoporotic effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protective Effect of Oxytocin Against Bone Loss in a Female Rat Model of Osteoporosis. Moghazy, H., Abdeen Mahmoud, A., Elbadre, H., et al.[2022]

Oxytocin is widely used during labor and delivery in Canada for inducing labor and controlling postpartum bleeding, but it is classified as a high-alert medication due to the risk of significant patient harm if misused.

Adverse effects from oxytocin can impact both mothers (such as arrhythmias and uterine hyperstimulation) and fetuses (including bradycardia and hypoxia), highlighting the need for careful management and monitoring during its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aggregate analysis of oxytocin incidents. [2016]

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]

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]

Oxytocin (OT) was found to stimulate the production of key cartilage components in vitro, suggesting it plays a role in promoting chondrogenesis, which is important for cartilage health.

In a clinical study involving 82 participants, lower serum levels of OT were significantly associated with hand osteoarthritis (OA), indicating that reduced OT may contribute to the development of OA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxytocin Controls Chondrogenesis and Correlates with Osteoarthritis. Roux, CH., Pisani, DF., Gillet, P., et al.[2021]

Oxytocin (OT) is produced not only in the brain but also by osteoblasts in the bone marrow, suggesting it plays a significant role in bone formation and may help regulate conditions like osteoarthritis (OA) where its levels are reduced.

OT has potential therapeutic benefits for OA due to its stimulatory effects on cartilage formation and its ability to mediate pain relief, making it a promising candidate for treating joint-related issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship between Oxytocin and Osteoarthritis: Hope or Despair? Ferrero, S., Amri, EZ., Roux, CH.[2021]

A case study highlights an allergic reaction to Syntocinon, a synthetic form of oxytocin, during a Caesarean section, indicating potential safety concerns with its use.

This incident underscores the importance of monitoring for allergic reactions when administering Syntocinon in surgical settings, even though it is commonly used to aid in uterine contraction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anaphylactoid reaction to oxytocin in pregnancy. Slater, RM., Bowles, BJ., Pumphrey, RS.[2019]

Carbetocin is as effective as syntometrine in preventing primary postpartum hemorrhage, with no significant difference in hemoglobin drop or the need for additional oxytocic injections among 329 women studied.

Carbetocin has a lower incidence of adverse effects such as nausea, vomiting, and hypertension compared to syntometrine, making it a safer alternative for managing the third stage of labor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised trial of carbetocin versus syntometrine in the management of the third stage of labour. Leung, SW., Ng, PS., Wong, WY., et al.[2021]

In a study involving 3497 women, the use of intramuscular oxytocin alone was found to be equally effective as oxytocin combined with ergometrine (Syntometrine) in reducing the risk of postpartum hemorrhage, indicating no significant advantage of the combination treatment.

However, the combination of oxytocin and ergometrine was associated with increased side effects such as nausea, vomiting, and elevated blood pressure, suggesting that routine use of this combination may not be beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised controlled trial of oxytocin alone versus oxytocin and ergometrine in active management of third stage of labour. McDonald, SJ., Prendiville, WJ., Blair, E.[2019]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8584067/

Relationship between Oxytocin and Osteoarthritis: Hope or ...

They found that leptin expression was higher in patients with knee OA and metabolic syndrome than in those with knee OA without metabolic syndrome [80]. These ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39920837/

Understanding Cognition, Oxytocin, and Pain in Elders (UCOPE)

This study will establish preliminary effectiveness of a novel intervention in middle to older aged adults with knee osteoarthritis pain.

3.

withpower.com

withpower.com/trial/phase-3-osteoarthritis-knee-10-2020-b6777

Oxytocin for Knee Osteoarthritis · Info for Participants

In a study involving ovariectomized (OVX) rats, oxytocin (OT) treatment for eight weeks helped maintain bone mass density (BMD) and prevented bone degeneration ...

4.

trialsjournal.biomedcentral.com

trialsjournal.biomedcentral.com/articles/10.1186/s13063-024-08715-4

Understanding Cognition, Oxytocin, and Pain in Elders (UCOPE)

This study will establish preliminary effectiveness of a novel intervention in middle to older aged adults with knee osteoarthritis pain.

5.

mdpi.com

mdpi.com/1422-0067/24/11/9750

The Association between Oxytocin and Lower Limb ...

This study aimed to investigate the serum OT level in hip and/or knee OA patients and to study its association with disease progression.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8429960/

Molecular Classification of Knee Osteoarthritis - PMC

Defining and evaluating a novel outcome measure representing end-stage knee osteoarthritis: data from the Osteoarthritis Initiative. Clin ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9718290/

A review of current clinical trials and developments

A placebo-controlled phase II study for TPX-100, showed that treatment was safe and improved knee function, with reduction in pain and disease ...

8.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04427540

Oxytocin Pharmacokinetics After Intramuscular Injection

In this study people with knee arthritis so severe that a joint replacement is needed are recruited for a one day study. Participants will come to the Clinical ...

9.

trials.arthritis.org

trials.arthritis.org/trials/NCT03878589

Understanding Cognition, Oxytocin & Pain in Elders

This study will test the efficacy and safety of self-administered intranasal OT over 4-weeks in older individuals with knee osteoarthritis. Relative to placebo ...