Coagulation and Fibrinolysis of Estradiol in Transwomen

December 19, 2022 updated by: Jenna Sarvaideo, Medical College of Wisconsin

Coagulation Activation and Fibrinolysis With Sublingual Versus Oral Versus Transdermal Estradiol in Transgender Women

The specific aim for our study is to measure coagulation system activation and fibrinolysis following transdermal versus sublingual versus oral estradiol versus in transgender women.

Hypothesis: Transdermal estradiol will result in less coagulation system activation and no effect on plasminogen activator inhibitor (PAI-1) or tissue-type plasminogen activator (t-PA). Oral estradiol will result in the most coagulation system activation and effect on PAI-1 and t-PA: Oral estradiol > sublingual estradiol > transdermal estradiol.

A prospective crossover study will include ten subjects given estradiol 1 mg daily and instructed to take it orally, sublingually, or transdermal for 2 months with a 2-week washout period between routes of administration. Labs will be measured 7 times during the study.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Subjects will report to our Adult Translational Research Unit for labs at baseline (2 weeks after HRT washout if needed). Both fibrinolysis and testosterone labs have a diurnal variation. Therefore, fasting labs will be drawn at approximately 8 AM. Five subjects will start oral estradiol and 5 will start sublingual estradiol for 8 weeks. Froedtert's Pharmacy Investigational Drug Service will provide the study estradiol. There will be a 2-week washout period between treatment periods. Fasting labs will be drawn at approximately 8 AM prior to Treatment Period 2. The groups will switch therapy. Those that took oral estradiol during Treatment Period 1 will take sublingual estradiol for 8 weeks. Those that took sublingual estradiol during Treatment Period 1 will take oral estradiol for 8 weeks. Finally, all subjects will start the transdermal for 8 weeks for Treatment Period 3. Final set of labs will be drawn at approximately 8 AM 2 weeks after Treatment Period 3. The investigators will call subjects every 2 weeks to assess their adherence to the treatment protocol and remind them of the importance of allowing the tablet to dissolve when taking estradiol sublingually.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Froedtert Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • 18 years or older
  • Gender identity of male to female or transwoman

Exclusion Criteria:

  • Liver disease
  • History of blood clot
  • Bleeding disorder
  • Active or recent (e.g., within the past year) stroke
  • Myocardial infarction,
  • History of orchiectomy
  • History of breast cancer,
  • Known sensitivity or allergy to any components of the medications used
  • Currently taking a potent CYP3A4 inhibitor or inducer.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Sublingual Estradiol
Sublingual estradiol administered for 8 weeks
Drug: Estradiol Tablets
Oral estradiol will be taken sublingually, 1 mg BID for 8 weeks
Other Names:
  • Sublingual estradiol tablets
Drug: Estradiol Tablets
Oral estradiol 1 mg BID for 8 weeks
Other Names:
  • Oral Estradiol tablets
Active Comparator: Oral Estradiol
Oral estradiol administered for 8 weeks
Drug: Estradiol Tablets
Oral estradiol will be taken sublingually, 1 mg BID for 8 weeks
Other Names:
  • Sublingual estradiol tablets
Drug: Estradiol Tablets
Oral estradiol 1 mg BID for 8 weeks
Other Names:
  • Oral Estradiol tablets
Active Comparator: Transdermal Estradiol
Transdermal estradiol administered for 8 weeks
Drug: Transdermal patch
Estradiol patch therapy for 8 weeks
Other Names:
  • Transdermal estradiol patch

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Coagulation system activation and fibrinolysis due to estradiol administration
Time Frame: 8 months
Comparison of morning fasting labs (fibrinogen, von-Willebrand Factor (vWF) ristocetin cofactor, vWF antigen, D-dimer, protein C activity, free protein S activity, Factors VII, VIII, IX, thrombin generation, plasminogen activator inhibitor (PAI-1), tissue-type plasminogen activator (t-PA) and t-PA activity) in transgender women taking estradiol via different routes of administration. Our hypothesis is that transdermal estradiol will result in less coagulation system activation and no effect on PAI-1 or t-PA. Oral estradiol will result in the most coagulation system activation and will effect PAI-1 and t-PA: Oral estradiol > sublingual estradiol > transdermal estradiol.
8 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Thrombotic risk due to estradiol administration
Time Frame: 8 months
Thrombotic risk will be assessed in transgender women by measuring estrone and thrombin generation and comparing them between the different routes of estradiol administration (transdermal versus sublingual versus oral).
8 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical College of Wisconsin

Investigators

  • Principal Investigator: Jenna Sarvaideo, DO, Medical College of Wisconsin

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 7, 2021

Primary Completion (Actual)

November 23, 2022

Study Completion (Actual)

November 23, 2022

Study Registration Dates

First Submitted

April 16, 2022

First Submitted That Met QC Criteria

May 19, 2022

First Posted (Actual)

May 24, 2022

Study Record Updates

Last Update Posted (Estimate)

December 21, 2022

Last Update Submitted That Met QC Criteria

December 19, 2022

Last Verified

December 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRO00036346

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

All individual participant data that underlie results in a publication.

IPD Sharing Time Frame

starting 3 months after publication

IPD Sharing Access Criteria

IPD will be shared if PI is directly contacted and asked for the above information.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)
  • Clinical Study Report (CSR)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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