Oxytocin for Ehlers-Danlos Syndrome

(EDS-OXY Trial)

Overseen By Keren Machol, MD, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: Baylor College of Medicine

Must not be taking: Hormonal contraceptives

Disqualifiers: Pregnancy, Lactation, Autoimmune disorders, others

Compensation: Varies

Number of Visits: 6

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stay on a stable regimen for pain control, meaning you should not change your current pain medications during the study.

What data supports the effectiveness of the drug oxytocin for treating Ehlers-Danlos Syndrome?

Research suggests that oxytocin may help manage pain, as it has been studied for its potential to reduce pain perception in conditions like chronic pain and fibromyalgia. However, results are mixed, and in some cases, oxytocin did not show positive effects, indicating that its effectiveness can vary. ^{1 2 3 4 5}

How does the drug oxytocin differ from other treatments for Ehlers-Danlos Syndrome?

Oxytocin is unique because it is a naturally occurring hormone that is being explored for its potential pain-relieving properties, which could be beneficial for managing chronic pain associated with Ehlers-Danlos Syndrome. Unlike traditional pain medications, oxytocin is non-addictive and has few adverse side effects, making it a novel option for pain management. ^{2 6 7 8 9}

What is the purpose of this trial?

This trial is testing if a treatment can help reduce long-term pain in women with a specific condition. The treatment might work by influencing how the body processes pain and emotions. It has been increasingly investigated for its potential in pain relief, with initial studies focusing on its effects during labor and breastfeeding.

Research Team

Brendan Lee, MD, PhD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for premenopausal females over 18 with hypermobile Ehlers-Danlos syndrome who experience chronic pain in multiple joints. Participants must have a stable pain management regimen and agree to use non-hormonal contraception. Excluded are those with certain heart conditions, autoimmune disorders causing joint inflammation, pregnancy, lactation, or allergies to oxytocin.

Inclusion Criteria

I have had pain greater than 4/10 in my back, neck, or joints most days in the last 3 months.

I have had pain greater than 4/10 in my back, neck, or joints most days in the last 3 months.

My pain medication dose is stable and won't increase during the study.

Exclusion Criteria

I have a history of heart rhythm problems, except for harmless fast or slow beats.

Your heart beats too fast or too slow, even when resting.

I have been diagnosed with an autoimmune disorder that causes joint pain.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Period 1

Participants receive either placebo or oxytocin infusion over three consecutive days, with daily subjective pain evaluation and monitoring using ACTIHEART device.

3 weeks

3 visits (in-person)

Washout Period

A one-month period between the two treatment phases to eliminate the effects of the first treatment.

4 weeks

Treatment Period 2

Participants receive the alternate treatment (placebo or oxytocin) over three consecutive days, with daily subjective pain evaluation and monitoring using ACTIHEART device.

3 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of anxiety, depression, and pain levels.

2 weeks

Treatment Details

Interventions

• Oxytocin
• Placebo

Trial Overview The study tests the effect of intravenous oxytocin on chronic pain against a placebo in patients with Hypermobile Ehlers-Danlos Syndrome (hEDS). It's designed to see if oxytocin can reduce their pain levels more effectively than a placebo.

Participant Groups

Group I: Oxytocin Active Control 1 Intervention

Treatment infusion: IV 1IU Oxytocin in 200ml of 0.9% NaCl, rate is 200ml over 40 minutes. Total of three infusions in three consecutive days (one per day)

Group II: Placebo Placebo Group 1 Intervention

Placebo infusion: IV 0.9% NaCl, rate is 200ml over 40 minutes. Total of three infusions in three consecutive days (one per day)

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?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Findings from Research

A systematic review and meta-analysis of 15 studies found that intranasal oxytocin (OXT) did not significantly reduce pain intensity or unpleasantness in human subjects, suggesting limited efficacy as a pain treatment.

The lack of significant results may be due to study designs not being sensitive enough to detect minor analgesic effects of OXT, which could vary based on the type and context of pain experienced.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of intranasal oxytocin on pain perception among human subjects: A systematic literature review and meta-analysis. Lopes, S., Osório, FL.[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]

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]

In a study involving 14 women with fibromyalgia, oxytocin nasal spray did not show significant therapeutic benefits in reducing pain, anxiety, or depression over a 3-week period compared to placebo.

Despite the lack of efficacy, oxytocin was found to be safe, with no reported toxicity, suggesting it could be a low-risk option for further exploration in fibromyalgia treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxytocin nasal spray in fibromyalgic patients. Mameli, S., Pisanu, GM., Sardo, S., et al.[2021]

In a study involving 24 individuals with chronic neck and shoulder pain (CNSP) and 24 healthy controls, intranasal oxytocin increased the perception of pain intensity in women with CNSP, indicating a potential hyperalgesic effect.

The results suggest that oxytocin may interact with sex hormones to influence pain perception, highlighting the need for caution in using oxytocin as a treatment for chronic pain, especially in women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex-specific effects of intranasal oxytocin on thermal pain perception: A randomised, double-blind, placebo-controlled cross-over study. Tracy, LM., Labuschagne, I., Georgiou-Karistianis, N., et al.[2018]

In a double-blind trial involving 29 out-patients over a minimum of 7 weeks, daily administration of 300 IU of synthetic oxytocin significantly improved sexual interest and capability compared to placebo, with statistically significant results (P < 0.05 for sexual interest).

The higher dose of 600 IU did not show any significant therapeutic effects, and both dosages of oxytocin were well tolerated with no reported side effects, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new approach to the hormonal treatment of impotentia erectionis. Lidberg, L., Sternthal, V.[2009]

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]

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]

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]

References

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

Effects of intranasal oxytocin on pain perception among human subjects: A systematic literature review and meta-analysis. [2023]

2. 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]

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

Anti-nociceptive effects of oxytocin receptor modulation in healthy volunteers-A randomized, double-blinded, placebo-controlled study. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Oxytocin nasal spray in fibromyalgic patients. [2021]

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

Sex-specific effects of intranasal oxytocin on thermal pain perception: A randomised, double-blind, placebo-controlled cross-over study. [2018]

6. Germany pubmed.ncbi.nlm.nih.gov

A new approach to the hormonal treatment of impotentia erectionis. [2009]

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

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

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

Synthetic oxytocin. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Anaphylactoid reaction to oxytocin in pregnancy. [2019]