Aspirin for Endometriosis

Overseen By Sue Slimak, RN

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Penn State University

Must be taking: Aspirin

Must not be taking: Antihypertensives, Diuretics, Digoxin

Disqualifiers: Cardiovascular disease, Diabetes, Hypertension, 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: 1

Duration: 1 day

96 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to compare neurovascular regulation in women with endometriosis and healthy women. The main questions it aims to answer are: * Do women with endometriosis have greater blood pressure and pain responses to a stimulus than healthy women? * Do women with endometriosis have greater platelet activity than healthy women? Participants will take aspirin and/or placebo and will: * perform hand grip exercise and cold pressor tests * undergo iontophoresis and blood draw Researchers will compare women with and without endometriosis to see if there is a difference in neurovascular regulation.

Will I have to stop taking my current medications?

The trial requires that you stop taking any current medications that could affect cardiovascular responses, such as blood pressure medications or diuretics.

What evidence supports the effectiveness of aspirin as a drug for endometriosis?

Aspirin is known for its pain-relieving and anti-inflammatory effects, which may help with endometriosis symptoms. It has been used effectively in other conditions like preeclampsia and coronary artery disease, suggesting potential benefits for endometriosis. ^{1 2 3 4 5}

Is aspirin generally safe for humans?

Aspirin, also known as acetylsalicylic acid, is widely used and generally considered safe for most people when taken as directed. It is commonly used to relieve pain and reduce inflammation, but like any medication, it can have side effects, such as stomach upset or increased bleeding risk, especially at higher doses. ^{6 7 8 9 10}

How does the drug aspirin differ from other treatments for endometriosis?

Aspirin is unique in its potential use for endometriosis due to its anti-inflammatory and antiplatelet properties, which are well-documented in other conditions like cardiovascular diseases and preeclampsia. Unlike standard endometriosis treatments, aspirin's ability to inhibit platelet aggregation and reduce inflammation might offer a novel approach to managing symptoms. ^{1 2 3 4 11}

Eligibility Criteria

This trial is for women aged 18-45, with or without endometriosis. It's not suitable for those who are pregnant, breastfeeding, have a high BMI or certain health conditions like cardiovascular disease, diabetes, severe liver or kidney issues, hypertension/hypotension, Raynaud's syndrome; those on medications affecting blood pressure; smokers; recent hormone therapy users; and individuals with skin allergies.

Inclusion Criteria

I was born with a uterus.

With and without endometriosis

Exclusion Criteria

Currently pregnant or breastfeeding

Allergy or hypersensitivity to investigational agents

I have been diagnosed with a heart condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single dose of aspirin or placebo and perform hand grip exercise and cold pressor tests, undergo iontophoresis and blood draw

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

Treatment Details

Interventions

• Aspirin
• Placebo

Trial Overview The study tests how aspirin affects blood pressure and pain in response to stress in women with endometriosis compared to healthy women. Participants will take aspirin or a placebo and undergo exercises and tests to measure neurovascular regulation differences between the two groups.

Participant Groups

Group I: Aspirin Experimental Treatment 1 Intervention

one dose of aspirin

Group II: Placebo Placebo Group 1 Intervention

Placebo pill

Aspirin is already approved in European Union, United States, Canada, China for the following indications:

Approved in European Union as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in United States as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in Canada as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in China as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention

Who Is Running the Clinical Trial?

Penn State University

Lead Sponsor

Trials

380

Recruited

131,000+

Findings from Research

Aspirin (ASA) significantly inhibits the growth of endometrial cancer cells (Ishikawa cells) in vitro, with growth inhibition ranging from 21% to 88% at concentrations of 1-5 mM over 96 hours.

The mechanism of action includes inducing apoptosis and reducing bcl-2 expression, with higher concentrations of ASA leading to increased apoptosis and a shift in the cell cycle from the resting phase to the S phase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aspirin effects on endometrial cancer cell growth. Arango, HA., Icely, S., Roberts, WS., et al.[2019]

A systematic review of studies indicates that low-dose aspirin (80-150 mg daily) taken in the first trimester (before 16 weeks) may effectively reduce the severity of preeclampsia in at-risk pregnancies.

In contrast, studies administering aspirin later in pregnancy showed mixed results, suggesting that the timing and dosage of aspirin are crucial for its effectiveness in preventing preeclampsia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The Role of Aspirin in Preeclampsia Prevention: State of the Art]. Campos, A.[2018]

Aspirin is considered safe for use during pregnancy at daily doses not exceeding 100mg and has been shown to effectively prevent pre-eclampsia and fetal growth restriction in high-risk patients.

However, aspirin has not demonstrated benefits for preventing vascular placental disease in low-risk patients or for unexplained recurrent miscarriages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Aspirin: Indications and use during pregnancy]. Belhomme, N., Doudnikoff, C., Polard, E., et al.[2018]

In a study of 189 subjects, only those who underwent surgical extraction while taking 81 mg of aspirin (ASA) showed bleeding after 24 hours, indicating a potential risk associated with surgical procedures.

However, the study concluded that patients taking daily aspirin could safely undergo simple dental extractions without significant bleeding risks, as no bleeding was observed in the other groups after 48 hours and 5 days post-operation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of aspirin on bleeding after extraction of teeth. Nooh, N.[2022]

In a study of 206 patients undergoing coronary artery bypass grafting (CABG), continuing aspirin (ASA) until the day of surgery significantly increased bleeding rates and the need for blood transfusions compared to stopping ASA 4 days prior to surgery.

Despite the increased bleeding and longer hospital stays in patients who continued ASA, there was no difference in serious postoperative complications like myocardial infarction or stroke, suggesting that stopping ASA before surgery may be safer without compromising outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Sustained Use of Aspirin until the Time of Surgery on Outcomes following Coronary Artery Bypass Grafting: A Randomized Clinical Trial. Sharifi, M., Kamali, A., Ghandi, Y.[2018]

In a study involving 40 female rabbits with experimentally induced peritoneal endometriosis, intralesional injection of 20% aspirin led to significant destruction of endometriosis foci, showing its potential as an effective treatment.

Histopathological analysis revealed that aspirin-treated groups exhibited extensive necrosis and significantly smaller remaining endometriosis areas compared to control groups, indicating a strong therapeutic effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of peritoneal endometriosis treatment using intralesional acetylsalicylic acid injection in rabbits. Saad-Hossne, R., Barretto, AB., Siqueira, JM., et al.[2019]

Low-dose aspirin treatment in endometriosis rat models significantly increased the expression of progesterone receptors and leukemia inhibitory factor (LIF), which are important for improving endometrial receptivity during the implantation window.

The study suggests that low-dose aspirin may help overcome progesterone resistance in endometriosis, potentially enhancing pregnancy rates in affected individuals, making it a promising treatment option for endometriosis-related infertility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose aspirin can downregulate progesterone resistance and increase the expression of LIF in endometriosis during the implantation window. Wang, L., Zhang, J., Zhang, H., et al.[2022]

Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) significantly increase the expression of the MRP4 transporter in human endometriotic epithelial cells, which is linked to the regulation of inflammation in endometriosis.

The increase in MRP4 expression due to NSAID treatment is dependent on the activation of the PPARa receptor, and this process is associated with higher levels of PGE2, suggesting a mechanism by which these drugs may influence endometriosis pathology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-steroidal anti-inflammatory drugs increase MRP4 expression in an endometriotic epithelial cell line in a PPARa dependent manner. Massimi, I., Pulcinelli, FM., Piscitelli, VP., et al.[2019]

Celecoxib significantly inhibited the proliferation of endometrial epithelial cells (EECs) and induced apoptosis in both control and endometriosis patients, indicating its potential as a therapeutic option for endometriosis.

The drug also reduced COX-2 activity and vascular endothelial growth factor (VEGF) secretion in EECs from endometriosis patients, suggesting that celecoxib may help manage endometrial growth through its anti-inflammatory properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a selective cyclooxygenase-2 inhibitor on endometrial epithelial cells from patients with endometriosis. Olivares, C., Bilotas, M., Buquet, R., et al.[2019]

Ursolic acid (UA) has been identified as a natural inhibitor of COX-2, significantly reducing cell viability and proliferation in human endometriotic stromal cells, while promoting apoptosis in a dose-dependent manner.

UA also decreases the production of COX-2 and prostaglandin E2 (PGE2), as well as vascular endothelial growth factor (VEGF), thereby inhibiting angiogenesis, which is crucial for the progression of endometriosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suppressive Effects of Ursolic Acid on Human Endometriotic Stromal Cells Survival. Li, J., Zeng, Z., Chang, Y., et al.[2023]

Aspirin, celebrating its 100-year anniversary, is now recognized for its crucial role in treating cardiovascular and cerebrovascular diseases by irreversibly inhibiting thromboxane A2, which helps prevent blood clots.

While aspirin effectively reduces risks in patients with existing heart and brain conditions, its use for primary prevention is controversial due to a lack of overall mortality reduction and potential serious side effects, such as increased bleeding, especially at higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Acetylsalicylic acid in the treatment of cardiovascular and cerebrovascular diseases]. Landmark, K.[2013]

References

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

Aspirin effects on endometrial cancer cell growth. [2019]

2. Portugal pubmed.ncbi.nlm.nih.gov

[The Role of Aspirin in Preeclampsia Prevention: State of the Art]. [2018]

3. France pubmed.ncbi.nlm.nih.gov

[Aspirin: Indications and use during pregnancy]. [2018]

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

The effect of aspirin on bleeding after extraction of teeth. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Effect of Sustained Use of Aspirin until the Time of Surgery on Outcomes following Coronary Artery Bypass Grafting: A Randomized Clinical Trial. [2018]

6. Brazil pubmed.ncbi.nlm.nih.gov

Evaluation of peritoneal endometriosis treatment using intralesional acetylsalicylic acid injection in rabbits. [2019]

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

Low-dose aspirin can downregulate progesterone resistance and increase the expression of LIF in endometriosis during the implantation window. [2022]

8. Italy pubmed.ncbi.nlm.nih.gov

Non-steroidal anti-inflammatory drugs increase MRP4 expression in an endometriotic epithelial cell line in a PPARa dependent manner. [2019]

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

Effects of a selective cyclooxygenase-2 inhibitor on endometrial epithelial cells from patients with endometriosis. [2019]

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

Suppressive Effects of Ursolic Acid on Human Endometriotic Stromal Cells Survival. [2023]

11. Norway pubmed.ncbi.nlm.nih.gov

[Acetylsalicylic acid in the treatment of cardiovascular and cerebrovascular diseases]. [2013]