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

38 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is a study of participants that will receive an intravenous (IV) infusion of oxytocin (naturally occurring hormone that is made in the brain). In this study healthy volunteers and people with knee arthritis so severe that they may need joint replacement are recruited for a one day study. Each study participant will have an IV catheter placed. After placement of the IV catheter oxytocin will be given by IV infusion. Investigators will perform some tests to evaluate how oxytocin changes perceptions on the skin. Investigators will study a painful perception by placing a probe on the skin and heating it to 113 -117 degrees Fahrenheit (F) for 5 minutes. Each study participant will score any pain that is experienced on a 0 to 10 scale, and most people find that pain rises during the 5 minutes, but remains mild, usually around only 1 or 2 on the 0 to 10 scale. The 5 minute heating temperature will be determined according to the subjects pain rating during the screening visit. The main goal of the study is to determine the effect of oxytocin during and after a fixed rate intravenous infusion on reduction in pain to a sustained heat stimulus in order to generate a model for peripheral analgesia.

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 oxytocin generally safe for use in humans?

Oxytocin, also known as Syntocinon, has been widely used in obstetrics with no side effects observed in a large study of 3,342 patients. However, there have been reports of allergic reactions and potential serious issues if misused, especially during labor, which can affect both the mother and baby. ^{1 2 3 4 5}

How is the drug oxytocin unique for treating knee osteoarthritis?

Oxytocin is unique for treating knee osteoarthritis because it may help with bone and cartilage health by promoting chondrogenesis (the formation of cartilage) and has potential pain-relieving effects, unlike traditional treatments that often focus only on pain relief. Additionally, oxytocin can be administered intranasally, which is a non-invasive method compared to other treatments. ^{1 6 7 8 9}

What data supports the effectiveness of the drug oxytocin for knee osteoarthritis?

Research suggests that oxytocin may help with bone health and has a role in reducing inflammation, which is important in osteoarthritis. It also seems to help with pain relief, making it a potential option for treating osteoarthritis. ^{1 4 7 9 10}

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: Oxytocin Experimental Treatment 1 Intervention

Oxytocin administered by IV infusion

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

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]

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 (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]

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]

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]

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]

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]

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]

Citations

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

Synthetic oxytocin. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Variations in oxytocin regimes in Scottish labour wards in 1998. [2004]

3. Iran pubmed.ncbi.nlm.nih.gov

Protective Effect of Oxytocin Against Bone Loss in a Female Rat Model of Osteoporosis. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Relationship between Oxytocin and Osteoarthritis: Hope or Despair? [2021]

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

Randomised controlled trial of oxytocin alone versus oxytocin and ergometrine in active management of third stage of labour. [2019]

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

A randomised trial of carbetocin versus syntometrine in the management of the third stage of labour. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Anaphylactoid reaction to oxytocin in pregnancy. [2019]

8. Canada pubmed.ncbi.nlm.nih.gov

Aggregate analysis of oxytocin incidents. [2016]

9. England 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. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Oxytocin Controls Chondrogenesis and Correlates with Osteoarthritis. [2021]