Feminizing Hormone Therapy and the Rectal Mucosa Immune Environment in Transgender Women

NCT04531943 | Completed FDA Drug

• 3 other identifiers: IRB00112414R01AI147839R21AI157911
• Study Type: observational
• Target: 285
• Locations: 1 country
• Sites: 1

Brief Summary

The overarching goal of this research study is to achieve a better understanding of the rectal mucosal effects of feminizing hormones in people assigned male sex at birth and currently taking feminizing hormones who have sex with men. Better understanding the rectal mucosa in this population will allow for the optimization of current biomedical HIV prevention interventions and enhance design of future interventions, including an effective HIV vaccine. This study will recruit approximately 520 transgender women who have receptive anal intercourse with men (TGWSM) and cis-gender men into one of two cohorts. Cohort 1 is a cross-sectional study and Cohort 2 is a longitudinal study; enrollment into each cohort is based on participant characteristics.

Conditions

HIV Prevention

Keywords

Transgender women

Outcome Measures

Primary Outcomes (8)

• Percent of Rectal Mucosal Cluster of Differentiation 4 (CD4+) T Cells Expressing C-C Chemokine Receptor Type 5 (CCR5) in Cohort 1

  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)

• Change in Percent of Rectal Mucosal CD4+ T cells expressing CCR5 in Cohort 2

  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.

  Baseline and up to 12 months after initiation of feminizing hormone therapy

• Production of p24 from Rectal Mucosal Explant Challenge in Cohort 1

  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.

  Day 1 (day of rectal mucosal sampling)

• Change in Production of p24 from Rectal Mucosal Explant Challenge in Cohort 2

  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.

  Baseline and up to 12 months after initiation of feminizing hormone therapy

• Relative abundance of Prevotellaceae in Cohort 1

  The median relative abundance of Prevotellaceae measured from rectal mucosal secretions will be compared between groups in Cohort 1.

  Day 1 (day of rectal mucosal sampling)

• Change in Relative abundance of Prevotellaceae in Cohort 2

  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.

  Baseline and up to 12 months after initiation of feminizing hormone therapy

• Relative abundance of Bacteroidaceae in Cohort 1

  The median relative abundance of Bacteroidaceae measured from rectal mucosal secretions will be compared between groups in Cohort 1.

  Day 1 (day of rectal mucosal sampling)

• Change in Relative abundance of Bacteroidaceae in Cohort 2

  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.

  Baseline and up to 12 months after initiation of feminizing hormone therapy

Study Arms (4)

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.

Drug: Estrogen

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.

Drug: Estrogen plus Progesterone

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.

Drug: Estrogen; Drug: Estrogen plus Progesterone

Interventions

Estrogen DRUG

Feminizing hormone therapy consisting of estrogen alone, as prescribed by the participant's healthcare provider.

TGWSM Initiating Feminizing Hormone Therapy; TGWSM Using Estrogen

Estrogen plus Progesterone DRUG

Feminizing hormone therapy consisting of estrogen and progesterone, as prescribed by the participant's healthcare provider.

TGWSM Initiating Feminizing Hormone Therapy; TGWSM Using Estrogen plus Progesterone

Eligibility Criteria

• Age: 18 Years - 59 Years
• Gender Eligibility Details: Participants are assigned male sex at birth and currently using feminizing hormones (Cohort 1, Group 1) or planning to begin using feminizing hormones (Cohort 2). Cisgender males are also enrolling.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

A total of 520 HIV-negative TGWSM and cisgender MSM will be enrolled into one of two cohorts.

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Emory University: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Hope Clinic

Atlanta, Georgia, 30030, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood and rectal mucosa samples will be collected.

MeSH Terms

Interventions

Estrogens; Progesterone

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Progesterone Congeners; Gonadal Steroid Hormones

Study Officials

• Colleen Kelley, MD, MPH

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 26, 2020
• First Posted: August 31, 2020
• Study Start: October 1, 2020
• Primary Completion: April 4, 2024
• Study Completion: April 4, 2024
• Last Updated: June 17, 2025

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will be made available to researchers providing a methodologically sound proposal, beginning 9 months and ending 36 months following publication.
• Access Criteria: Proposals should be directed to colleen.kelley@emory.edu. To gain access, data requestors will need to sign a data access agreement.

Locations

US (1)