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TREAT: Transgender Estradiol Affirming Therapy

Sponsor
Washington University School of Medicine (Other)
Overall Status
Recruiting
CT.gov ID
NCT05010707
Collaborator
(none)
45
Enrollment
1
Location
3
Arms
35
Anticipated Duration (Months)
1.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this open label, pilot, randomized clinical trial is to evaluate the effectiveness, safety and tolerability of estrogen use in transgender female and the degree of testosterone suppression achieved in this population when placed on gender affirming pharmacological therapy.

Condition or Disease Intervention/Treatment Phase
  • Drug: Transdermal patch
  • Diagnostic Test: Pro-thrombotic markers
  • Diagnostic Test: Metabolic markers
  • Diagnostic Test: Hormone Profile
  • Drug: Sublingual Tablet
  • Drug: Sublingual Tablet
  • Drug: Spironolactone
 Phase 3

Detailed Description

Transgender patients suffer from poor mental and medical health outcomes compared to their cisgender peers. Given the widespread acknowledgment of the health care needs of transgender people, priority should be given to those actions that will ensure safe and appropriate care in health centers.

The current hormone therapy is not uniform and depends on the health care system, cost considerations, and differences in the regional availability of estrogens and antiandrogens. A typical regimen includes estrogen to provide feminizing effects in conjunction with therapy to block testosterone (antiandrogens or gonadotropin-releasing hormone [GnRH] analogs). Estrogen also inhibits testosterone secretion.

Ethinyl estradiol was previously the mainstay of most estrogen-directed therapies; this is no longer the case due to its increased risk of cardiovascular death and increased incidence of deep venous thrombosis. 17-beta estradiol, which can be provided in tablet, patch, and injection, is currently the preferred formulation.

This open label, pilot, randomized clinical trial will evaluate the effectiveness and safety of gender affirming hormone therapy with estrogen and the degree of testosterone suppression achieved in transgender female patients when placed on daily sublingual 17-beta estradiol, twice daily sublingual 17-beta estradiol, or transdermal 17-beta estradiol. All patients will also receive spironolactone as antiandrogen.

One of the major complications from estradiol GAHT is thromboembolism. The investigators will also determine the effects of the different estradiol regimens on thrombosis markers. These studies will be the first to determine if the dosing regimen of estradiol affects risk markers in transgender women.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
45 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Participants who agreed to be in the study will undergo block randomization into three groups: daily sublingual 17 beta estradiol twice daily sublingual 17 beta estradiol transdermal 17 beta estradiol All patients will also receive spironolactone as antiandrogen.Participants who agreed to be in the study will undergo block randomization into three groups:daily sublingual 17 beta estradiol twice daily sublingual 17 beta estradiol transdermal 17 beta estradiol All patients will also receive spironolactone as antiandrogen.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Effectiveness and Safety of Different Estradiol Replacement Therapies in Transgender Female
Actual Study Start Date :
Aug 2, 2021
Anticipated Primary Completion Date :
Jul 1, 2024
Anticipated Study Completion Date :
Jul 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Transdermal estradiol plus spironolactone

Starting dose will be 100 mcg/24hrs Plan to increase by 100 mcg/24hrs every month to a max dose of 400 mcg/24hrs Goal is to achieve a serum estradiol level between 100-200 pg/mL and to suppress testosterone to cisgender female levels All patients will also receive spironolactone. Spironolactone will be started at 50 mg daily and will increase to standard dose.

Drug: Transdermal patch
Participants will be prescribed the medication and dosed based on their hormonal profile. Goal is achieve estradiol level between 100-200 pg/mL and to suppress testosterone to cisgender female levels

Diagnostic Test: Pro-thrombotic markers
Once participants are started on gender affirming hormone therapy, pro-thombotic markers will be checked at baseline and every 6 months. Pro-thrombotic markers will include: Factor II, Factor IX, Factor XI, Von Willebrand factor, Protein C, Protein S, activated Protein C resistance.

Diagnostic Test: Metabolic markers
Once participants are started on gender affirming hormone therapy, metabolic markers will be checked at baseline and every 6 months. Markers will include: Insulin level, fasting glucose, body mass index, waist circumference.

Diagnostic Test: Hormone Profile
Once participants are started on gender affirming hormone therapy, hormonal levels will be checked every 4 weeks until estradiol and testosterone levels are within goal as established by standard of care.

Drug: Spironolactone
All patients will also receive spironolactone. Spironolactone will be started at 50 mg daily and will increase to standard dose.
Active Comparator: Daily sublingual estradiol plus spironolactone

Starting dose will be 2 mg daily Plan to increase every month by 2 mg daily Goal is to achieve serum estradiol level between 100-200 pg/mL mL and to suppress testosterone to cisgender female levels. All patients will also receive spironolactone. Spironolactone will be started at 50 mg daily and will increase to standard dose. Spironolactone will be started at 50 mg daily and will increase to standard dose.

Diagnostic Test: Pro-thrombotic markers
Once participants are started on gender affirming hormone therapy, pro-thombotic markers will be checked at baseline and every 6 months. Pro-thrombotic markers will include: Factor II, Factor IX, Factor XI, Von Willebrand factor, Protein C, Protein S, activated Protein C resistance.

Diagnostic Test: Metabolic markers
Once participants are started on gender affirming hormone therapy, metabolic markers will be checked at baseline and every 6 months. Markers will include: Insulin level, fasting glucose, body mass index, waist circumference.

Diagnostic Test: Hormone Profile
Once participants are started on gender affirming hormone therapy, hormonal levels will be checked every 4 weeks until estradiol and testosterone levels are within goal as established by standard of care.

Drug: Sublingual Tablet
Participants will be prescribed the medication and dosed based on their hormonal profile. Participants will take dose as once daily medication. Goal is achieve estradiol level between 100-200 pg/mL and to suppress testosterone to cisgender female levels
Other Names:
  • Once daily dosing

    • Drug: Spironolactone
    All patients will also receive spironolactone. Spironolactone will be started at 50 mg daily and will increase to standard dose.
    Active Comparator: Twice daily sublingual estradiol plus spironolactone

    Starting dose will be 1 mg twice daily Plan to increase every month by 2 mg daily divided BID Goal is to achieve serum estradiol level between 100-200 pg/mL mL and to suppress testosterone to cisgender female levels All patients will also receive spironolactone. Spironolactone will be started at 50 mg daily and will increase to standard dose. Spironolactone will be started at 50 mg daily and will increase to standard dose.

    Diagnostic Test: Pro-thrombotic markers
    Once participants are started on gender affirming hormone therapy, pro-thombotic markers will be checked at baseline and every 6 months. Pro-thrombotic markers will include: Factor II, Factor IX, Factor XI, Von Willebrand factor, Protein C, Protein S, activated Protein C resistance.

    Diagnostic Test: Metabolic markers
    Once participants are started on gender affirming hormone therapy, metabolic markers will be checked at baseline and every 6 months. Markers will include: Insulin level, fasting glucose, body mass index, waist circumference.

    Diagnostic Test: Hormone Profile
    Once participants are started on gender affirming hormone therapy, hormonal levels will be checked every 4 weeks until estradiol and testosterone levels are within goal as established by standard of care.

    Drug: Sublingual Tablet
    Participants will be prescribed the medication and dosed based on their hormonal profile. Participants will take dose as twice daily medication. Goal is achieve estradiol level between 100-200 pg/mL and to suppress testosterone to cisgender female levels
    Other Names:
  • Twice daily dosing

    • Drug: Spironolactone
    All patients will also receive spironolactone. Spironolactone will be started at 50 mg daily and will increase to standard dose.

    Outcome Measures

    Primary Outcome Measures

    1. Degree of testosterone suppression by measuring total testosterone level in transgender female patients undergoing hormonal affirming therapy [Change from baseline total testosterone level at 6,12,18, and 24 months]

    Secondary Outcome Measures

    1. Coagulation factors II, IX, XI, Protein C, Protein S, von Willebrand factor, and activated protein C resistance in transgender female patients undergoing [Change from baseline factor II, IX, XI, Protein C, Protein S, von Willebrand factor, and activated protein C resistance level at 6,12,18, and 24 months]

    2. von Willebrand factor in transgender female patients undergoing [Change from baseline von Willebrand factor antigen level at 6,12,18, and 24 months]

    3. Llipid panel [Changes from baseline lipid panel at 12 and 24 months]

    4. Homeostatic Model Assessment for Insulin Resistance [Change from baseline HOMA-IR at 6,12,18, and 24 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 30 Years
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
    • Female transgender patients between the ages of 18 to 30 years of age who are seen at the Washington University Transgender Center. Patients must have met the eligibility and readiness criteria for gender-affirming hormone therapy.
    Exclusion Criteria:

    • GnRH agonist for the last 12 months

    • History of liver disease

    • Dyslipidemia requiring treatment

    • Cigarette smoking

    • Body mass index >30 kg/m2

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Washington University Transgender Center Saint Louis Missouri United States 63112

    Sponsors and Collaborators

    • Washington University School of Medicine

    Investigators

    • Principal Investigator: Ginger Nicol, MD, Washington University School of Medicine

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Ginger E Nicol, Associate Professor of Child & Adolescent Psychiatry, Washington University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT05010707
    Other Study ID Numbers:
    • 202104092
    First Posted:
    Aug 18, 2021
    Last Update Posted:
    Aug 18, 2021
    Last Verified:
    Aug 1, 2021
    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
    Keywords provided by Ginger E Nicol, Associate Professor of Child & Adolescent Psychiatry, Washington University School of Medicine
    Transgender female
    Gender affirming hormone therapy
    Estrogen therapy
    Additional relevant MeSH terms:
    Spironolactone
    Hormones

    Study Results

    No Results Posted as of Aug 18, 2021