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

Trial Summary

What is the purpose of this trial?

The purpose of the study is to learn more about the role of blood clotting factor proteins and cells in menstrual (period) bleeding. The investigators are hoping to identify differences in these proteins and cells in the menstrual blood of individuals with heavy periods compared to menstruating individuals who do not have heavy periods.

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 data supports the effectiveness of the treatment Sample Collection and Endometrial Biopsy, Endometrial Sampling, Uterine Biopsy for heavy menstrual bleeding?

Research shows that endometrial sampling, like Pipelle biopsy, is accurate in diagnosing conditions related to abnormal uterine bleeding, which can help guide effective treatment for heavy menstrual bleeding. ^{1 2 3 4 5}

Is endometrial sampling safe for humans?

Pipelle endometrial sampling is considered safe, with studies showing it is less invasive and associated with fewer complications compared to other methods like dilation and curettage. It can be performed in an office setting and is generally well-tolerated by patients. ^{4 5 6 7 8}

How is the treatment of Sample Collection and Endometrial Biopsy unique for heavy menstrual bleeding?

This treatment is unique because it involves collecting samples from the uterus lining (endometrial biopsy) to analyze clotting factors, which can help understand the causes of heavy menstrual bleeding. Unlike other treatments that may focus on medication or surgery, this approach aims to diagnose the underlying issue by examining the tissue directly. ^{1 2 5 9 10}

Eligibility Criteria

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.

Inclusion Criteria

I am between 18-45 years old and have regular menstrual cycles.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Endometrial fibrinolytic enzymes in women with normal menstruation and dysfunctional uterine bleeding. [2019]

2. Pakistan pubmed.ncbi.nlm.nih.gov

Morphological study of Pipelle biopsy specimens in cases of abnormal uterine bleeding. [2015]

3. Germany pubmed.ncbi.nlm.nih.gov

Could body mass index be an indicator for endometrial biopsy in premenopausal women with heavy menstrual bleeding? [2022]

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

The accuracy of endometrial Pipelle sampling with and without sonographic measurement of endometrial thickness. [2016]

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

Factors affecting adequacy of Pipelle and Tao Brush endometrial sampling. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Pipelle endometrial sampling success rates in Kazakhstani settings: results from a prospective cohort analysis. [2022]

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

Endometrial receptivity and conception outcome among women with light menstrual bleeding of unidentified etiology. [2018]

8. Germany pubmed.ncbi.nlm.nih.gov

Endometrial haemostasis and menstruation. [2022]

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

A simple visual assessment technique to discriminate between menorrhagia and normal menstrual blood loss. [2022]

10. England 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. [2022]