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

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how well oxytocin, a hormone often linked to social bonding, can reduce chronic pain in people with Hypermobile Ehlers-Danlos Syndrome (hEDS). Participants will receive either oxytocin or a placebo through an IV in a carefully controlled sequence. The trial seeks premenopausal women with hEDS who have experienced significant pain in multiple joints for at least three months. As a Phase 1/Phase 2 trial, this research aims to understand how the treatment works and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking research.

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.

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

Research has shown that oxytocin is usually well-tolerated. In past studies, participants received both low and high doses of oxytocin without any reported side effects. These findings suggest that oxytocin might be safe for humans, but further research is necessary to confirm this. The current trial is investigating whether oxytocin can help with chronic pain in individuals with Hypermobile Ehlers-Danlos Syndrome, though the research is still in its early stages. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Ehlers-Danlos syndrome?

Unlike the standard treatments for Ehlers-Danlos Syndrome, which often involve pain management with medications like NSAIDs or physical therapy, the study drug oxytocin offers a unique approach. Oxytocin is a hormone that, beyond its well-known role in childbirth and social bonding, may affect connective tissue properties, potentially addressing a core issue in Ehlers-Danlos Syndrome. Researchers are excited because oxytocin could directly target the connective tissue abnormalities that characterize this condition, offering a novel mechanism of action compared to current options.

What evidence suggests that oxytocin might be an effective treatment for chronic pain in Ehlers-Danlos syndrome?

Research has shown that oxytocin, a hormone aiding social connections, might also reduce chronic pain in individuals with Hypermobile Ehlers-Danlos syndrome. Early studies on humans suggest that oxytocin can lower pain sensitivity, potentially helping people feel less pain. Although clinical data remains limited, initial results are promising and suggest that oxytocin could effectively manage pain in this condition. Participants in this trial will receive both placebo and oxytocin in a fixed sequence to evaluate its effectiveness. ^{4 5 6 7 8}

Who Is on the Research Team?

Brendan Lee, MD, PhD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Placebo-Oxytocin sequence Experimental Treatment 2 Interventions

In this single blind fixed sequence study participants were treated with Placebo infusion: IV 0.9% NaCl, rate is 200ml over 40 minutes once a day for three consecutive days (one per day) and a after a washout of at least a month 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)

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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]

Citations

1. withpower.com withpower.com/trial/phase-2-ehlers-danlos-syndrome-4-2022-ff804

Oxytocin for Ehlers-Danlos Syndrome (EDS-OXY Trial) 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6994142/

Targetable cellular signaling events mediate vascular ... Moreover, treatment with a specific oxytocin receptor antagonist (35) led to enhanced postpartum survival (~90%) (Figure 5C), directly implicating oxytocin ...

3. patents.google.com patents.google.com/patent/CA3196923A1/en

Oxytocin treatment for hypermobile ehlers-danlos syndrome Preliminary research with humans offers consistent evidence to suggest that oxytocin decreases pain sensitivity. oxytocin on chronic pain and its functional ...

4. trials.arthritis.org trials.arthritis.org/trials/NCT05405257

Oxytocin for Hypermobile Ehlers-Danlos Syndrome Study Purpose. The purpose of this pilot study is to evaluate effect of IV oxytocin on chronic pain in patients with Hypermobile Ehlers Danlos syndrome.

5. obgyn.onlinelibrary.wiley.com obgyn.onlinelibrary.wiley.com/doi/full/10.1034/j.1600-0412.2002.810403.x

Pregnancy and the Ehlers–Danlos syndrome: a retrospective ... Preterm delivery occurred in 21% of the affected mothers compared with 40% of the nonaffected women with an affected infant; the women with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05405257?cond=Ehlers-Danlos%20syndrome%20OR%20%22Danlos%20disease%22%20OR%20%22%20Danlos%20Disease,%20Ehlers%22%20OR%20%22%20danlos%20ehlers%20syndrome%22%20OR%20%22%20Disease,%20Ehlers%20Danlos%22%20OR%20%22%20Disease,%20Ehlers-Danlos%22%20OR%20%22%20Dystrophia%20mesodermalis%20congenita%22%20OR%20%22%20EDS%22%20OR%20%22%20Ehler%20Danlos%20Syndrome%22%20OR%20%22%20Ehlers%20Danlos%20Disease%22%20OR%20%22%20ehlers%20danlos%20syndrome%22%20OR%20%22%20Ehlers-Danlos%20Disease%22%20OR%20%22%20Ehlers-Danlos%20syndromes%22%20OR%20%22%20elastic%20skin%22%20OR%20%22%20Fibrodysplasia%20elastica%20generalisata%22%20OR%20%22%20Hereditary%20collagen%20dysplasia%22%20OR%20%22%20Meekeren-Ehlers-Danlos%20syndrome%22%20OR%20%22%20skin%20elastic%22%20OR%20%22%20Syndrome,%20Ehlers-Danlos%22&aggFilters=status:not%20rec&viewType=Table&rank=5

Oxytocin for Hypermobile Ehlers-Danlos Syndrome Data collected at the beginning of a clinical study for all participants and for each arm or comparison group. These data include demographics, such as age, sex ...

7. ctv.veeva.com ctv.veeva.com/study/oxytocin-for-hypermobile-ehlers-danlos-syndrome

Oxytocin for Hypermobile Ehlers-Danlos Syndrome (EDS-OXY) The purpose of this pilot study is to evaluate effect of IV oxytocin on chronic pain in patients with Hypermobile Ehlers Danlos syndrome.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6134354/

Hypermobile Ehlers–Danlos syndrome and pregnancy - PMC Overall, pregnancy is well tolerated in hEDS. Possible complications are mainly attributable to joint hypermobility, skin and tissue fragility and abnormal ...