Sexually Transmitted Diseases
Conditions
Keywords
Prevention, STI, Post-exposure prophylaxis, HIV, PEP
Brief summary
The goal of this project is to collect data regarding the ability of various oral doses of doxycycline to penetrate mucosal tissues in men and women to inform the combination of doxycycline with antiretrovirals (ARVs) for the development of single-dose event-driven multipurpose prevention strategies to protect against HIV and sexually transmitted infections (STIs). This study is of importance in the field of research because it allows the exploration of new dosing strategies that would permit a single event-driven oral dose of medications that could provide protection from HIV as well as other STIs. The study population that this study seeks to enroll are healthy people assigned male or female sex at birth and not using gender-affirming hormone therapy and are willing to undergo study procedures. Recruitment: Both face-to-face and online engagements will be conducted to recruit study participants. Face-to-face locations include bars and nightclubs, community organizations serving study populations, sports events, and community venues, and online engagements include dating sites, social networks, and craigslist, amongst other social medial platforms.
Detailed description
The incidence of bacterial STIs is increasing and studies have recently shown that Doxy-PEP can reduce the incidence of bacterial STIs among men who have sex with men (MSM) and Doxy-PEP is being explored for STI prevention among women. A better understanding of mucosal drug penetration of doxycycline will inform the design of future studies to prevent STIs in various populations. The purpose of this study is to understand how well doxycycline taken by mouth gets to the tissues of the rectum and vagina. Researchers think doxycycline could be used to treat sexually transmitted infections (STIs) caused by bacteria. To understand better, they want to see how well doxycycline reaches the tissues affected by STIs. The study procedures include the collection of past and present medical history, and biological specimen sampling such as blood, rectal and vaginal fluids, tissue biopsies, and urine. Study participants will also be administered an investigational agent (doxycycline not yet approved for this indication). The duration of this clinical trial for study participants will be approximately 8 weeks.
Interventions
DRUGDoxycycline
Doxycycline is used to treat or prevent infections that are strongly suspected to be caused by bacteria; it is an antimicrobial drug indicated for bacterial infections such as sexually transmitted infections. Doxycycline (DOX) will be given orally at 100 and 200 mg doses.
Sponsors
Centers for Disease Control and Prevention
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 59 Years
Healthy volunteers
Yes
Inclusion criteria
* Aged 18-59 years * Assigned male sex or female sex at birth * In good general health * Not currently taking doxycycline or other tetracycline-derived antibiotics and no plans to initiate during the study * For HIV-positive people, on stable antiretroviral therapy with an undetectable viral load and CD4 count\> 300ul/ml * Willing to use condoms consistently for the duration of the study * Able to provide informed consent * No plans for relocation in the next 4 months * Not pregnant and does not plan on getting pregnant for the duration of the study * Willing to undergo peripheral blood, urine, rectal or vaginal secretion collection, and a rectal or vaginal and cervical biopsy procedure * Willing to use study products as directed
Exclusion criteria
* Current or chronic history of liver disease * Continued need for, or use during the 90 days before enrollment, of the following medications: 1. Systemic immunomodulatory agents 2. Supraphysiologic doses of steroids (short course steroids less than 7 days duration, allowable at the discretion of the investigators) 3. Chemotherapy or radiation for treatment of malignancy 4. Experimental medications, vaccines, or biologicals * Intent to use doxycycline or other tetracycline-derived antibiotics during the study, outside of the study procedures * 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 * Known allergic reaction to study drugs. * Significant laboratory abnormalities at baseline visit for rectal biopsies, including but not limited to: 1. Hgb ≤ 10 g/dL 2. PTT \> 1.5x ULN or INR \> 1.5x ULN 3. Platelet count \<100,000
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Doxycycline Concentrations in Rectal Tissues | Day 2 | Rectal biopsies were collected 24 hours after administration of the initial dose of doxycycline |
| Doxycycline Concentrations in Vaginal Tissues | Day 2 | Vaginal biopsies collected 24 hours after administration of the initial dose of doxycycline |
| Doxycycline Concentrations in Rectal Tissues After the Fifth Dose of Doxycycline | Day 15 | Self-collected swabs and rectal biopsies were collected 24 hours after administration of the fifth dose of doxycycline |
| Doxycycline Concentrations in Vaginal Tissues Collected 24 Hours After the Fifth Dose of Doxycycline | Day 15 | Self-collected swabs and vaginal biopsies were collected 24 hours after administration of the fifth dose of doxycycline |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes in Doxycycline Concentrations in Rectal Secretions in Participants Taking 5 Doses of Doxycycline. | Throughout study up to 3 months after fifth dose | Self-collected and staff assisted vaginal swabs will be collected at each in person visit |
| Changes in Blood Doxycycline Concentrations in Participants Taking 5 Doses of Doxycycline. | Throughout study up to 3 months after fifth dose | Blood samples will be taken at each in person visit |
| Changes in Doxycycline Concentrations in Penile Secretions in Participants Taking 5 Doses of Doxycycline. | Throughout study up to 3 months after fifth dose | Staff-Assisted urethral and glans swabs will be collected |
| Changes in Urine Doxycycline Concentrations in Participants Taking 5 Doses of Doxycycline. | Throughout study up to 3 months after fifth dose | Urine samples will be taken at each in person visit |
| Changes in Doxycycline Concentrations in Throat Secretions in Participants Taking 5 Doses of Doxycycline. | Throughout study up to 3 months after fifth dose | Self-collected swab samples will be collected 24 hours after administration of the first dose. |
| Changes in Doxycycline Concentrations in Vaginal Secretions in Participants Taking 5 Doses of Doxycycline. | Throughout study up to 3 months after fifth dose | Self-collected vaginal swabs will be collected at each in person visit |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from Emory Healthcare System in Atlanta, Georgia, USA. Participant enrollment began May 31, 2023, and all follow-up was completed by December 24, 2024.
Participants by arm
| Arm | Count |
|---|---|
| Doxycycline 100 mg Doxycycline 100mg Participants will receive the first assigned dose of Doxycycline at the clinic on days 0 and 3 at the clinic. The other three doses of the medication will be taken at home on days 7 and 1
Doxycycline: Doxycycline is used to treat or prevent infections that are strongly suspected to be caused by bacteria; it is an antimicrobial drug indicated for bacterial infections such as sexually transmitted infections. Doxycycline (DOX) will be given orally at 100 and 200 mg doses. | 26 |
| Doxycycline 200 mg Doxycycline - 200 mg Participants will receive the first assigned dose of Doxycycline at the clinic on days 0 and 3 at the clinic. The other three doses of the medication will be taken at home on days 7 and 10
Doxycycline: Doxycycline is used to treat or prevent infections that are strongly suspected to be caused by bacteria; it is an antimicrobial drug indicated for bacterial infections such as sexually transmitted infections. Doxycycline (DOX) will be given orally at 100 and 200 mg doses. | 19 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 4 | 4 |
| Overall Study | Physician Decision | 3 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 2 |
Baseline characteristics
| Characteristic | Doxycycline 100 mg | Doxycycline 200 mg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants | 19 Participants | 45 Participants |
| Age, Continuous | 40.7 years STANDARD_DEVIATION 12.1 | 35.4 years STANDARD_DEVIATION 9.2 | 38.5 years STANDARD_DEVIATION 11.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 18 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 9 Participants | 22 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 6 Participants | 14 Participants |
| Region of Enrollment United States | 26 Participants | 19 Participants | 45 Participants |
| Sex: Female, Male Female | 7 Participants | 10 Participants | 17 Participants |
| Sex: Female, Male Male | 19 Participants | 9 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 19 |
| other Total, other adverse events | 0 / 26 | 0 / 19 |
| serious Total, serious adverse events | 0 / 26 | 0 / 19 |
Outcome results
Primary
Doxycycline Concentrations in Rectal Tissues
Rectal biopsies were collected 24 hours after administration of the initial dose of doxycycline
Time frame: Day 2
Population: Participants who completed the corresponding study visit and provided samples for processing.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Doxycycline 100 mg | Doxycycline Concentrations in Rectal Tissues | 0.863 µg/g |
| Doxycycline 200 mg | Doxycycline Concentrations in Rectal Tissues | 2.193 µg/g |
Primary
Doxycycline Concentrations in Rectal Tissues After the Fifth Dose of Doxycycline
Self-collected swabs and rectal biopsies were collected 24 hours after administration of the fifth dose of doxycycline
Time frame: Day 15
Population: Participants who completed the corresponding study visit and provided samples for processing.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Doxycycline 100 mg | Doxycycline Concentrations in Rectal Tissues After the Fifth Dose of Doxycycline | 0.951 µg/g |
| Doxycycline 200 mg | Doxycycline Concentrations in Rectal Tissues After the Fifth Dose of Doxycycline | 1.612 µg/g |
Primary
Doxycycline Concentrations in Vaginal Tissues
Vaginal biopsies collected 24 hours after administration of the initial dose of doxycycline
Time frame: Day 2
Population: Participants who completed the corresponding study visit and provided samples for processing
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Doxycycline 100 mg | Doxycycline Concentrations in Vaginal Tissues | 0.592 µg/g |
| Doxycycline 200 mg | Doxycycline Concentrations in Vaginal Tissues | 1.214 µg/g |
Primary
Doxycycline Concentrations in Vaginal Tissues Collected 24 Hours After the Fifth Dose of Doxycycline
Self-collected swabs and vaginal biopsies were collected 24 hours after administration of the fifth dose of doxycycline
Time frame: Day 15
Population: Participants who completed the corresponding study visit and provided samples for processing.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Doxycycline 100 mg | Doxycycline Concentrations in Vaginal Tissues Collected 24 Hours After the Fifth Dose of Doxycycline | 0.590 µg/g |
| Doxycycline 200 mg | Doxycycline Concentrations in Vaginal Tissues Collected 24 Hours After the Fifth Dose of Doxycycline | 1.534 µg/g |
Other Pre-specified
Changes in Blood Doxycycline Concentrations in Participants Taking 5 Doses of Doxycycline.
Blood samples will be taken at each in person visit
Time frame: Throughout study up to 3 months after fifth dose
Other Pre-specified
Changes in Doxycycline Concentrations in Penile Secretions in Participants Taking 5 Doses of Doxycycline.
Staff-Assisted urethral and glans swabs will be collected
Time frame: Throughout study up to 3 months after fifth dose
Other Pre-specified
Changes in Doxycycline Concentrations in Rectal Secretions in Participants Taking 5 Doses of Doxycycline.
Self-collected and staff assisted vaginal swabs will be collected at each in person visit
Time frame: Throughout study up to 3 months after fifth dose
Other Pre-specified
Changes in Doxycycline Concentrations in Throat Secretions in Participants Taking 5 Doses of Doxycycline.
Self-collected swab samples will be collected 24 hours after administration of the first dose.
Time frame: Throughout study up to 3 months after fifth dose
Other Pre-specified
Changes in Doxycycline Concentrations in Vaginal Secretions in Participants Taking 5 Doses of Doxycycline.
Self-collected vaginal swabs will be collected at each in person visit
Time frame: Throughout study up to 3 months after fifth dose
Other Pre-specified
Changes in Urine Doxycycline Concentrations in Participants Taking 5 Doses of Doxycycline.
Urine samples will be taken at each in person visit
Time frame: Throughout study up to 3 months after fifth dose