Clotting Factors Analysis for Heavy Menstrual Bleeding

Overseen By Women's Health Research Unit Department of Ob/Gyn

Age: 18 - 65

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: Oregon Health and Science University

Must not be taking: Hormonal contraceptives, Antifibrinolytics, Anticoagulants

Disqualifiers: Pregnancy, Lactating, Bleeding disorder, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates the role of blood clotting factors in menstrual bleeding. Researchers aim to identify differences in these factors between individuals with heavy menstrual bleeding and those with regular periods. Participants will provide daily samples of menstrual blood for one cycle and undergo a single endometrial biopsy (a small tissue sample from the uterus). This trial suits individuals who experience either heavy or regular menstrual bleeding without using hormonal contraceptives or certain medications. As a Phase 1 and Phase 2 trial, the research focuses on understanding how the treatment works and measuring 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 stop using hormonal contraceptives, copper IUDs, antifibrinolytics, and anticoagulants before participating.

What prior data suggests that this sample collection and endometrial biopsy is safe?

Research shows that an endometrial biopsy is a safe procedure often used to examine the tissue lining the uterus, particularly when irregular bleeding occurs. Studies have found it effective for women with and without bleeding disorders.

Most patients handle the procedure well, though some might experience mild discomfort or cramping. Serious complications are rare. In this study, the procedure will collect samples from participants with both heavy and regular menstrual bleeding to help researchers learn about differences in clotting factors.

Collecting samples involves a simple process of gathering menstrual blood, which is non-invasive and safe. Overall, available evidence considers the procedures in this study safe and well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it aims to uncover insights into the clotting factors involved in heavy menstrual bleeding, which could lead to more targeted treatments in the future. Unlike standard treatments like hormonal therapies or tranexamic acid, which mainly address symptoms, this trial focuses on understanding the underlying biological mechanisms. By analyzing daily menstrual blood samples and conducting endometrial biopsies, researchers hope to identify specific factors that contribute to heavy bleeding, paving the way for more effective and personalized interventions.

What evidence suggests that this sample collection and endometrial biopsy is effective for analyzing heavy menstrual bleeding?

Research shows that an endometrial biopsy is a safe and effective way to examine the lining of the uterus. Doctors often use this method to investigate unusual uterine bleeding, such as heavy periods, to determine the cause. Studies have found that this type of biopsy can successfully identify issues in the uterine lining that might lead to heavy menstrual bleeding. In this trial, participants with heavy menstrual bleeding will undergo an endometrial biopsy to help understand and manage their condition. Although the study remains in its early stages, endometrial biopsies have already proven helpful in understanding and managing abnormal bleeding. This suggests the treatment could provide valuable information about heavy menstrual bleeding. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for menstruating individuals aged 18-45 who experience heavy menstrual bleeding. It aims to understand the role of certain proteins and cells in period bleeding by comparing them with those from individuals without heavy periods.

Exclusion Criteria

I have a diagnosed condition causing heavy menstrual bleeding.

I am willing to abstain from sex for two weeks before my biopsy.

I have a bleeding disorder or I'm on blood thinners.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Sample Collection

Participants provide daily samples of menstrual blood for a single cycle and undergo a single endometrial biopsy for HEEC culture

4 weeks

Daily sample collection, 1 visit for biopsy

Analysis

Coagulation factors are measured in menstrual blood and mRNA for these factors is quantified from cultured HEECs

4 weeks

Follow-up

Participants are monitored for changes in the Pictorial Blood Loss Assessment Charts and mRNA copies from HEEC culture

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sample Collection and Endometrial Biopsy

Trial Overview The study involves collecting samples and performing an endometrial biopsy to analyze blood clotting factor proteins like PAI-1, tPA, TFPI, and how they interact with cells called HEECs during menstrual bleeding.

How Is the Trial Designed?

Group I: Heavy Menstrual Bleeding Active Control 1 Intervention

Participants with heavy menstrual bleeding will provide daily samples of menstrual blood for a single cycle and undergo a single endometrial biopsy for HEEC culture.

Group II: Regular Mensural Bleeding Active Control 1 Intervention

Participants with normal menstrual bleeding will provide daily samples of menstrual blood for a single cycle and undergo a single endometrial biopsy for HEEC culture.

Sample Collection and Endometrial Biopsy is already approved in United States, European Union for the following indications:

Approved in United States as Endometrial Biopsy for:

• Abnormal uterine bleeding
• Postmenopausal bleeding
• Endometrial hyperplasia
• Cancer screening

Approved in European Union as Endometrial Biopsy for:

• Heavy menstrual bleeding
• Irregular uterine bleeding
• Postmenopausal bleeding
• Endometrial hyperplasia
• Cancer screening

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

Published Research Related to This Trial

The Pipelle endometrial sampling method demonstrated a high success rate of 82.76% in a study of 87 patients in Kazakhstan, with the highest success observed in women of reproductive age experiencing abnormal uterine bleeding (93.19%).

Factors such as the indication for the biopsy, patients' age, BMI, and menopausal status significantly influenced the success rate, highlighting the need for careful consideration of these factors in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pipelle endometrial sampling success rates in Kazakhstani settings: results from a prospective cohort analysis. Terzic, M., Aimagambetova, G., Bapayeva, G., et al.[2022]

Women aged 20-35 with light menstrual bleeding of unknown cause showed significantly lower endometrial receptivity scores compared to a control group, indicating potential issues with their uterine lining.

These women also experienced lower conception rates (60% vs. 72.1%) and higher rates of early spontaneous abortion (34.4% vs. 18.1%), suggesting that light menstrual bleeding may negatively impact fertility outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endometrial receptivity and conception outcome among women with light menstrual bleeding of unidentified etiology. Gao, Y., Hong, X., Wang, Z., et al.[2018]

Pipelle endometrial sampling is highly accurate, with a 90% agreement in histologic results compared to curettage, and successfully identified all cases of endometrial cancer in the study of 176 patients.

In postmenopausal patients with abnormal uterine bleeding, the combination of Pipelle sampling and sonographic measurement of endometrial thickness resulted in 100% sensitivity and specificity, indicating its effectiveness in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The accuracy of endometrial Pipelle sampling with and without sonographic measurement of endometrial thickness. Goldchmit, R., Katz, Z., Blickstein, I., et al.[2016]

In women with dysfunctional uterine bleeding (DUB), higher levels of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor Type 1 (PAI-1) were found in the endometrium compared to women with normal menstruation, indicating a potential mechanism for increased menstrual blood loss.

A significant positive correlation was observed between endometrial t-PA activity and menstrual blood loss, suggesting that elevated t-PA activity may contribute to heavier menstrual bleeding in DUB cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endometrial fibrinolytic enzymes in women with normal menstruation and dysfunctional uterine bleeding. Gleeson, N., Devitt, M., Sheppard, BL., et al.[2019]

The study suggests that measuring glycodelin A (GdA) levels in endometrial secretion samples can effectively assess endometrial maturation, providing a less invasive alternative to traditional tissue biopsies.

This method correlates well with hormone levels (estradiol and progesterone) and may help in evaluating conditions related to conception without interfering with the implantation process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The feasibility of a less invasive method to assess endometrial maturation--comparison of simultaneously obtained uterine secretion and tissue biopsy. van der Gaast, MH., Macklon, NS., Beier-Hellwig, K., et al.[2022]

In a study of 1120 premenopausal women with heavy menstrual bleeding, those with a BMI of 30 or higher had a sevenfold increased risk of abnormal endometrial findings, including hyperplasia with atypia and carcinoma.

The study suggests that all women with a BMI ≥30 experiencing heavy menstrual bleeding should undergo an endometrial biopsy, regardless of their age, as BMI is a significant risk factor for endometrial abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Could body mass index be an indicator for endometrial biopsy in premenopausal women with heavy menstrual bleeding? Guraslan, H., Dogan, K., Kaya, C., et al.[2022]

Menstruation is a complex process regulated by hormones and involves a balance of coagulation and fibrinolysis to control bleeding; abnormalities in these processes can lead to heavy menstrual bleeding (HMB).

Research indicates that undiagnosed bleeding disorders, such as von Willebrand disease, can cause HMB, and treatments like tranexamic acid and DDAVP can effectively reduce menstrual blood loss by enhancing haemostasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endometrial haemostasis and menstruation. Davies, J., Kadir, RA.[2022]

In a study of 200 women at high risk for endometrial cancer, the Tao Brush was found to provide significantly more adequate endometrial samples compared to the Pipelle device, indicating its superior efficacy in this context.

Women preferred the Tao Brush over the Pipelle for endometrial sampling, suggesting better acceptability, particularly in postmenopausal women, where the Tao Brush should be considered as a preferred option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors affecting adequacy of Pipelle and Tao Brush endometrial sampling. Williams, AR., Brechin, S., Porter, AJ., et al.[2022]

In a study of 101 patients with abnormal uterine bleeding, the most common finding on Pipelle biopsy was proliferative endometrium, observed in 52.5% of cases, indicating that this is a prevalent condition among women experiencing such symptoms.

The Pipelle biopsy method was effective in identifying endometrial pathologies, particularly when the issues were widespread rather than localized, although it has some limitations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Morphological study of Pipelle biopsy specimens in cases of abnormal uterine bleeding. Khadim, MT., Zehra, T., Ashraf, HM.[2015]

A new visual assessment technique for measuring menstrual blood loss was validated, showing high predictive values for identifying menorrhagia, with positive and negative predictive values of 85.9% and 84.8%, respectively, based on a study of 288 women and 489 menstrual episodes.

This method outperformed women's subjective assessments and anemia indicators in predicting menorrhagia, suggesting it can improve treatment quality by providing a more accurate diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A simple visual assessment technique to discriminate between menorrhagia and normal menstrual blood loss. Janssen, CA., Scholten, PC., Heintz, AP.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5879845/

Abnormal Uterine Bleeding- evaluation by Endometrial ... Endometrial aspiration is a simple, safe, and effective method to sample endometrium in cases of AUB avoiding risk of anesthesia and is less time-consuming.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2590161325000043

Endometrial biopsy in younger women with abnormal ... In our study, ET > 15 mm was associated with a statistically significant increased risk of EH/EC and can be considered as a tool to triage AUB patients at high ...

3. aafp.org aafp.org/pubs/afp/issues/2020/0501/p551.html

Endometrial Biopsy: Tips and Pitfalls Endometrial biopsy is a safe and efficient method to evaluate the endometrium for a variety of indications, most commonly abnormal uterine bleeding and ...

4. cureus.com cureus.com/articles/116217-a-histopathological-study-of-endometrial-biopsy-samples-in-abnormal-uterine-bleeding

A Histopathological Study of Endometrial Biopsy Samples ... In this study, 71.25% presented with the complaint of menorrhagia. This was the most common presenting complaint in both reproductive and ...

5. mdpi.com mdpi.com/2077-0383/13/14/4048

Results of Endometrial Biopsy and Its Impact on Survival ... In this study, the term AUB refers exclusively to intermenstrual bleeding and postmenopausal bleeding. Heavy uterine bleeding was not added to ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2468784723000557

Review Endometrial biopsy: Indications, techniques and ... An adequate tissue sampling is mandatory when performing an EB. Blind methods should not be first choice in patients with suspected endometrial malignancy.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9731800/

A Histopathological Study of Endometrial Biopsy Samples ... It was observed that menorrhagia was the most common bleeding pattern accounting for 71.25% cases. Hypomenorrhea was the least common bleeding ...

8. mountsinai.org mountsinai.org/health-library/tests/endometrial-biopsy

Endometrial biopsy Information | Mount Sinai - New York Learn about Endometrial biopsy, find a doctor, complications, outcomes, recovery and follow-up care for Endometrial biopsy.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6142441/

Heavy menstrual bleeding: work-up and management - PMC In a study comparing the procedure in 41 women with bleeding disorders with 111 women without, the procedure was found to be equally successful in both groups.