Oxytocin for Sunburn Pain

Overseen By Regina Curry, RN

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Wake Forest University Health Sciences

Must not be taking: Benzodiazepines, Pain medications, SSRIs, MAOIs

Disqualifiers: Skin cancer, Diabetes, Hyponatremia, others

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: 2

Duration: 1 day

36 Participants Needed

Trial Summary

What is the purpose of this trial?

This study aims to answer the question: Does oxytocin increase the pain threshold on thermal heat pain in the presence of vibration on an area of skin exposed to a mild sunburn?

Will I have to stop taking my current medications?

If you are taking benzodiazepines, pain medications daily, or any of the listed medications like thiazide diuretics, lithium, or SSRIs, you may need to stop as these are part of the exclusion criteria. The trial does not specify a washout period, but you should discuss with the trial team to understand any necessary changes to your medication.

Is oxytocin safe for use in humans?

Oxytocin, also known as Syntocinon, has been used safely in thousands of patients for various medical purposes, with no significant side effects reported. Studies show it does not cause genetic damage and has a safety profile similar to other standard treatments. ^{1 2 3 4 5}

How does the drug oxytocin differ from other treatments for sunburn pain?

Oxytocin is unique for sunburn pain because it has antioxidant properties, which may help reduce inflammation and damage caused by oxidative stress, unlike typical sunburn treatments that mainly focus on soothing the skin or reducing pain. ^{6 7 8 9 10}

Research Team

James C Eisenach, M.D.

Principal Investigator

Wake Forest University Health Sciences

Eligibility Criteria

This trial is for men and women aged 18-55, with a BMI under 40, in good health as per the Principal Investigator's assessment. Participants should have light to medium skin tone (Fitzpatrick Scale I-III). Excluded are those with dark complexions, pregnant or breastfeeding individuals, latex allergy sufferers, history of skin cancer or chronic pain conditions like neuropathy or diabetes, certain heart conditions, hyponatremia risk factors or on specific medications.

Inclusion Criteria

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

Fitzpatrick Scale rating I through III

Exclusion Criteria

Dark enough skin complexion that would make it infeasible to determine the minimal erythematous dose of UV-B irradiation. Anyone Fitzpatrick Scale score greater than 3 will be excluded

Pregnancy or currently breast feeding

Subjects with a known latex allergy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive two 30-minute infusions of oxytocin or placebo, separated by 30 minutes, to test the effect on heat pain threshold after UV-B burn

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in heat pain threshold and touch/pain sensitivity using von Frey filament application

2 days

1 visit (in-person)

Treatment Details

Interventions

• Oxytocin

Trial Overview The study investigates if oxytocin can increase the threshold for feeling heat pain after a mild sunburn when combined with vibration therapy. It compares the effects of oxytocin against a placebo in this setting.

Participant Groups

Group I: oxytocin Experimental Treatment 1 Intervention

Two 30 minute infusions of oxytocin, 10 International Units (IU) separated by 30 minutes. To avoid potential unmasking by facial flushing which can occur at the beginning of high rates of oxytocin administration, the first infusion will consist of two steps beginning with a rate of 0.125 IU oxytocin per minute for 5 minutes, then increased to 0.375 IU oxytocin for 25 minutes. The second infusion will be a constant rate of 0.333 IU oxytocin per minute for 30 minutes.

Group II: placebo Placebo Group 1 Intervention

Two 30 minute infusions of placebo separated by 30 minutes. The first infusion will consist of two steps, using an equivalent volume of placebo fluid infusion as in the oxytocin arm. This will consist of a slower rate in the first 5 minutes and more rapid rate for the last 25 min. The second placebo solution infusion will be a constant rate and volume equivalent to that used in the oxytocin arm.

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+

Findings from Research

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]

High concentrations of oxytocin, the active component of Syntocinon, do not show any genotoxic effects in human peripheral blood lymphocyte cultures, indicating it does not cause damage to genetic material.

The study also found no significant changes in the mitotic index, suggesting that oxytocin does not have cytotoxic or mitogenic effects on these cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro cytogenetic analysis of the effects of oxytocin on human peripheral blood lymphocytes. Djelić, N., Soldatović, B., Andjelković, M., et al.[2019]

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]

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]

Carbetocin is likely as effective as oxytocin and syntometrine in preventing postpartum hemorrhage, based on a review of various studies that assessed multiple outcome measures.

The safety profile of carbetocin is similar to that of oxytocin, which is currently the standard treatment for this condition, although further research is necessary to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carbetocin for the prevention of postpartum hemorrhage: a systematic review. Peters, NC., Duvekot, JJ.[2018]

Cisplatin (CP) causes significant renal toxicity in male Wistar albino rats, evidenced by increased levels of urea, creatinine, and lactate dehydrogenase, along with histopathological damage to the kidneys.

Oxytocin (OT) administration significantly mitigated the nephrotoxic effects of CP, likely due to its antioxidant properties, as indicated by improved renal function markers and restored antioxidant enzyme activities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxytocin ameliorates cisplatin-induced nephrotoxicity in Wistar rats. Elberry, AA., Refaie, SM., Kamel, M., et al.[2021]

In a study involving 14 adult rats, oxytocin treatment significantly reduced renal damage caused by cisplatin, as evidenced by improved kidney histology and reduced inflammation markers.

Oxytocin's protective effect was linked to its ability to suppress C-reactive protein and TGF-β levels while enhancing Akt expression, highlighting its potential as a therapeutic agent against cisplatin-induced kidney injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxytocin alleviates cisplatin-induced renal damage in rats. Erbas, O., Anil Korkmaz, H., Oltulu, F., et al.[2022]

Oxytocin (OT) has been shown to significantly reduce nephrotoxicity caused by cisplatin (CP) by decreasing the expression of harmful enzymes like NADPH oxidase and P38 MAPK, which are involved in oxidative stress.

OT also enhances the levels of protective antioxidants in the kidneys, leading to reduced inflammation and tubular damage, ultimately improving kidney function after CP treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxytocin inhibits NADPH oxidase and P38 MAPK in cisplatin-induced nephrotoxicity. Rashed, LA., Hashem, RM., Soliman, HM.[2017]

In a Phase I study involving patients with various solid tumors, nogitecan hydrochloride (topotecan) demonstrated a maximum tolerated dose (MTD) of over 22.5 mg/m2 for single doses and 1.5 mg/m2 per day for a 5-day repeat dosing schedule, with reversible leucopenia identified as the dose-limiting factor.

The pharmacokinetics showed that plasma concentrations of nogitecan increased with dosage, and there was no accumulation during the 5-day dosing, leading to the selection of a 5-day repeat dose of 1.2 mg/m2 per day for further Phase II studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I studies of nogitecan hydrochloride for Japanese. Kobayashi, K., Hino, M., Fukuoka, M., et al.[2013]

The synthesized water-soluble 20(S)-glycinate esters of camptothecin analogues show comparable antitumor activity against breast cancer xenografts to the approved drug CPT-11, indicating their potential as effective cancer treatments.

Unlike CPT-11, these glycinate esters do not require carboxylesterase for activation, which may simplify their use in therapy and reduce potential side effects related to acetylcholinesterase inhibition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Water soluble 20(S)-glycinate esters of 10,11-methylenedioxycamptothecins are highly active against human breast cancer xenografts. Wadkins, RM., Potter, PM., Vladu, B., et al.[2018]

References

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

Synthetic oxytocin. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

In vitro cytogenetic analysis of the effects of oxytocin on human peripheral blood lymphocytes. [2019]

3. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

Carbetocin for the prevention of postpartum hemorrhage: a systematic review. [2018]

6. Saudi Arabia pubmed.ncbi.nlm.nih.gov

Oxytocin ameliorates cisplatin-induced nephrotoxicity in Wistar rats. [2021]

7. Iran pubmed.ncbi.nlm.nih.gov

Oxytocin alleviates cisplatin-induced renal damage in rats. [2022]

8. France pubmed.ncbi.nlm.nih.gov

Oxytocin inhibits NADPH oxidase and P38 MAPK in cisplatin-induced nephrotoxicity. [2017]

9. Japan pubmed.ncbi.nlm.nih.gov

Phase I studies of nogitecan hydrochloride for Japanese. [2013]

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

Water soluble 20(S)-glycinate esters of 10,11-methylenedioxycamptothecins are highly active against human breast cancer xenografts. [2018]