- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04531943
Feminizing Hormone Therapy and the Rectal Mucosa Immune Environment in Transgender Women
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Transgender women who have receptive anal intercourse with men (TGWSM; assigned male sex at birth and taking/planning to take feminizing hormone therapy) are at high risk of HIV, and many HIV infections occur due to exposure to the rectal mucosa. In this study, the researchers will examine the biologic effects of feminizing hormone therapy on the mucosal immune milieu of the rectum. A better understanding of rectal HIV transmission among TGWSM will lead to the development of improved biomedical prevention interventions.
Historically, TGWSM have been grouped with men who have sex with men (MSM) in HIV prevention studies due to presumed similar risks of rectal HIV exposure despite their unique psychosocial, biologic, and prevention needs. From a biologic perspective, many TGWSM use feminizing hormone therapy with uncertain rectal mucosal effects. The effects of endogenous and exogenous hormones in the human and animal-model female genital tract has been described with estrogen generally being seen as hindering HIV transmission and progesterone facilitating transmission; however, few studies report effects on the rectal mucosa. In addition, the intestinal mucosa is known to be steroidogenic, and colonic epithelial cells express estrogen receptor β, suggesting that exogenous hormone therapy likely has an effect on the rectal mucosa that could influence HIV transmission. For this project, the researchers will build upon our successful translational mucosal immunology program with a highly successful clinical research and retention infrastructure that was designed to understand factors that may influence rectal HIV transmission and propose to examine the effects of feminizing hormone therapy on the rectal mucosal resident cellular populations, transcriptome, and microbiome in TGWSM. In the rectal mucosa, the researchers will compare HIV target cell availability, the transcriptome, and microbiome in a cross-sectional cohort of 1) TGWSM on using feminizing hormone therapy (n=300) and 2) cisgender MSM (n=150). The researchers will also examine HIV target cell availability, the transcriptome, and microbiome in a longitudinal study of TGWSM (n=70) before and after initiating feminizing hormone therapy.
Two cohorts of HIV-negative TGWSM will be enrolled in this study. Cohort 1 will be a cross-sectional study where the researchers will enroll 300 TGWSM who are on feminizing hormone therapy and a control group of 150 sexually active cisgender men (assigned male sex at birth and currently identify as male) who have sex with men. Individuals in Cohort 1 will participate in study activities for up to 12 weeks. Cohort 2 is a longitudinal study where 70 TGWSM who are naïve to feminizing hormone therapy or have not taken feminizing hormone therapy for > 6 months and plan to initiate feminizing hormone therapy will be enrolled. Individuals in Cohort 2 will participate in study activities for 18 months.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Colleen Kelley, MD, MPH
- Phone Number: 404-712-1370
- Email: colleen.kelley@emory.edu
Study Locations
-
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Georgia
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Atlanta, Georgia, United States, 30030
- Recruiting
- Hope Clinic
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
INCLUSION CRITERIA
Cohort 1, TGWSM using feminizing hormone therapy
- Assigned male sex at birth and currently using feminizing hormone therapy
- Aged 18-59 years
- Able to provide informed consent in the official language of the study site's country
- HIV negative
- Receptive anal intercourse with a person assigned male sex at birth at least once in lifetime
Taking feminizing hormone therapy for at least the last 6 months with no change in dose for the last 3 months (i.e. no increase or decrease)
Feminizing hormone therapy is defined as use of oral, patch, topical, or injection estrogen therapy with or without progesterone therapy in people who were assigned male sex at birth but take feminizing hormones to affirm their current gender identity
- Approximately half of the cohort to be using estrogen therapy alone and half using estrogen+progesterone
- Anti-androgen therapy is permissive, but dose must also be stable for the last 3 months at the time of enrollment
- Willing to undergo peripheral blood and rectal biopsy sampling
- Willing to abstain from receptive anal intercourse for 72 hours before and for 1 week after rectal biopsy procedure
- Willing to answer sexual behavior questions
Cohort 1, Cisgender Males
- Assigned male sex at birth, currently identify as male gender (i.e. cisgender), man who has sex with men aged 18-59 years
- Able to provide informed consent in the official language of the study site's country
- HIV negative
- Receptive anal intercourse with a person assigned male sex at birth at least once in lifetime
- No history of taking supplemental steroids including testosterone replacement therapy in the last 12 months
- Willing to undergo peripheral blood and rectal biopsy sampling
- Willing to abstain from receptive anal intercourse for 72 hours before and for 1 week after rectal biopsy procedure.
- Willing to answer sexual behavior questions.
Cohort 2, Longitudinal study with TGWSM planning to initiate feminizing hormone therapy
- Assigned male sex at birth with plans to start feminizing hormone therapy
- Aged 18-59 years
- Able to provide informed consent in the official language of the study site's country
- Naïve to feminizing hormone therapy or no use in the last 6 months, including anti-androgen therapy.
- HIV negative
- Receptive anal intercourse with a person assigned male sex at birth at least once in lifetime
Plans to initiate feminizing hormone therapy in next 6 months.
- Feminizing hormone therapy is defined as use of oral, patch, topical, or injection estrogen therapy with or without progesterone therapy in people who were assigned male sex at birth but take feminizing hormones to affirm their current gender identity.
- Anti-androgen therapy is permissive, but participants must also be initiating estrogen therapy to be eligible.
- Willing to undergo peripheral blood and rectal biopsy sampling
- Willing to abstain from receptive anal intercourse for 72 hours before and for 1 week after rectal biopsy procedure.
- Willing to answer sexual behavior questions.
EXCLUSION CRITERIA
- History of inflammatory bowel disease or other inflammatory, infiltrative, infectious or vascular condition involving the lower gastrointestinal tract that, in the judgment of the investigators, may be worsened by study procedures or may significantly distort the anatomy of the distal large bowel
Significant laboratory abnormalities at baseline visit for rectal biopsies, including but not limited to:
- Hemoglobin (Hgb) ≤ 10 g/dL
- Partial thromboplastin time (PTT) > 1.5x upper limit of normal (ULN) or international normalised ratio (INR) > 1.5x ULN
- Platelet count <100,000
Any known medical condition that, in the judgment of the investigators, increases the risk of local or systemic complications of endoscopic procedures or pelvic examination, including but not limited to:
- Uncontrolled or severe cardiac arrhythmia
- Recent major abdominal, cardiothoracic, or neurological surgery in the last 12 months
- History of uncontrolled bleeding diathesis
- History of colonic, rectal, or vaginal perforation, fistula, or malignancy
- History or evidence on clinical examination of ulcerative, suppurative, or proliferative lesions of the anorectal mucosa.
Use of systemic (oral/IV) antibiotics within the 4 weeks prior to rectal mucosal sampling.
- Participants may be screened/enrolled who do not meet this criterion, but rectal mucosal sampling will be deferred for at least 4 weeks from last systemic antibiotic use.
Continued need for, or use during the 14 days prior to enrollment, of the following medications:
- Aspirin or more than 4 doses of nonsteroidal anti-inflammatory drugs (NSAIDs)
- Warfarin, heparin (low-molecular weight or unfractionated), platelet aggregation inhibitors, or fibrinolytic agents
- Any form of rectally administered agent besides products (lubricants or douching) used for sexual intercourse
Continued need for, or use during the 90 days prior to enrollment, of the following medications:
- Systemic immunomodulatory agents
- Supraphysiologic doses of steroids with the exception of short course steroids <7 days duration at the discretion of the investigator and feminizing hormone therapy as detailed in inclusion criteria
- Experimental medications, vaccines, or biologicals
- Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the study requirements.
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Other
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
TGWSM Using Estrogen
Cohort 1 participants are in the cross-sectional study and will attend two study visits, participating in study activities for up to 12 weeks.
Blood samples and rectal mucosal samples will be obtained.
This group of participants in Cohort 1 consists of TGWSM currently using feminizing hormone therapy consisting of only estrogen.
|
Feminizing hormone therapy consisting of estrogen alone, as prescribed by the participant's healthcare provider.
|
TGWSM Using Estrogen plus Progesterone
Cohort 1 participants are in the cross-sectional study and will attend two study visits, participating in study activities for up to 12 weeks.
Blood samples and rectal mucosal samples will be obtained.
This group of participants in Cohort 1 consists of TGWSM currently using feminizing hormone therapy consisting of estrogen and progesterone.
|
Feminizing hormone therapy consisting of estrogen and progesterone, as prescribed by the participant's healthcare provider.
|
Cisgender MSM
Cohort 1 participants are in the cross-sectional study and will attend two study visits, participating in study activities for up to 12 weeks.
Blood samples and rectal mucosal samples will be obtained.
This group of participants in Cohort 1 consists of cisgender MSM.
|
|
TGWSM Initiating Feminizing Hormone Therapy
Cohort 2 participants are in the longitudinal portion of the study and are TGWSM who are planning to initiate feminizing hormone therapy.
Individuals in Cohort 2 will participate in study activities for 18 months.
|
Feminizing hormone therapy consisting of estrogen alone, as prescribed by the participant's healthcare provider.
Feminizing hormone therapy consisting of estrogen and progesterone, as prescribed by the participant's healthcare provider.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent of Rectal Mucosal Cluster of Differentiation 4 (CD4+) T Cells Expressing C-C Chemokine Receptor Type 5 (CCR5) in Cohort 1
Time Frame: Day 1 (day of rectal mucosal sampling)
|
The median percentage of rectal mucosal CD4+ T cells that express CCR5 will be compared between groups in Cohort 1.
|
Day 1 (day of rectal mucosal sampling)
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Change in Percent of Rectal Mucosal CD4+ T cells expressing CCR5 in Cohort 2
Time Frame: Baseline and up to 12 months after initiation of feminizing hormone therapy
|
The median percentage of rectal mucosal CD4+ T cells that express CCR5 will be compared in Cohort 2, before hormone therapy begins and after hormone therapy.
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Baseline and up to 12 months after initiation of feminizing hormone therapy
|
Production of p24 from Rectal Mucosal Explant Challenge in Cohort 1
Time Frame: Day 1 (day of rectal mucosal sampling)
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The median production of p24 from rectal mucosal explant challenge experiments as measured by the area under the curve will be compared between groups in Cohort 1.
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Day 1 (day of rectal mucosal sampling)
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Change in Production of p24 from Rectal Mucosal Explant Challenge in Cohort 2
Time Frame: Baseline and up to 12 months after initiation of feminizing hormone therapy
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The median production of p24 from rectal mucosal explant challenge experiments as measured by the area under the curve will be compared in Cohort 2, before hormone therapy begins and after hormone therapy.
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Baseline and up to 12 months after initiation of feminizing hormone therapy
|
Relative abundance of Prevotellaceae in Cohort 1
Time Frame: Day 1 (day of rectal mucosal sampling)
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The median relative abundance of Prevotellaceae measured from rectal mucosal secretions will be compared between groups in Cohort 1.
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Day 1 (day of rectal mucosal sampling)
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Change in Relative abundance of Prevotellaceae in Cohort 2
Time Frame: Baseline and up to 12 months after initiation of feminizing hormone therapy
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The median relative abundance of Prevotellaceae measured from rectal mucosal secretions will be compared in Cohort 2, before hormone therapy begins and after hormone therapy.
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Baseline and up to 12 months after initiation of feminizing hormone therapy
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Relative abundance of Bacteroidaceae in Cohort 1
Time Frame: Day 1 (day of rectal mucosal sampling)
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The median relative abundance of Bacteroidaceae measured from rectal mucosal secretions will be compared between groups in Cohort 1.
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Day 1 (day of rectal mucosal sampling)
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Change in Relative abundance of Bacteroidaceae in Cohort 2
Time Frame: Baseline and up to 12 months after initiation of feminizing hormone therapy
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The median relative abundance of Bacteroidaceae measured from rectal mucosal secretions will be compared in Cohort 2, before hormone therapy begins and after hormone therapy.
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Baseline and up to 12 months after initiation of feminizing hormone therapy
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRB00112414
- R01AI147839 (U.S. NIH Grant/Contract)
- R21AI157911 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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