HIV-1-infectionPhase 1NCT03837015
Estrogen, Probiotics and Vaginal Health to Prevent HIV Infection in ACB Women
A Phase 1 study testing Estring Vaginal Ring and RepHresh Pro-B in people with HIV-1-infection and Bacterial Vaginoses, run by McMaster University at 1 site in Canada.
Trial summary
This study will enrol African, Caribbean and Black (ACB) women who are known to have a more diverse vaginal microbiome, higher rates of bacterial vaginosis with lower numbers of protective lactobacilli, and are at increased risk for HIV. Read more about this study
- Who is it for?
- Ages 18 to 49 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- HIV-1-infection, Bacterial Vaginoses
- What is being tested?
- Estring Vaginal Ring and RepHresh Pro-B
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteCanada
- Study dates
- 4 Nov 2019to 14 Dec 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 49 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- African, Caribbean, Black
- Pre-menopausal women in good general health, as determined by the investigator
- Uterus and cervix present
- Negative pregnancy test
- Currently practicing barrier or non-hormonal forms of contraception, and planning to continue, for the duration of the study (barrier contraceptive, abstinence)
- Willing to undergo a pelvic exam by a female nurse/female doctor
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- Willing to abstain from vaginal intercourse for 48 hours prior to sampling, over the entire course of the study
- Able to understand, comply and consent to protocol requirements and instructions
- Able to attend scheduled study visits and complete required investigations
Who cannot join
- Currently lactating
- Pregnant: suspected, current or in the last 12 months
- Irregular menstrual cycle (less than 6 periods in a year) not related to contraceptive use, pregnancy or breastfeeding
- Post-menopausal
- Hormonal Contraceptive use or other hormonal treatment in the past 3 months
- Current Intra-Uterine Device (IUD) use
Show all 42Show fewer
- Positive test result for Gonorrhea and/or Chlamydia
- Clinically obvious genital ulceration/lesions
- Symptomatic vaginal yeast infection or clinically significant vaginal discharge
- HIV-positive
- Any clinically significant abnormality on screening safety blood tests, that in the opinion of the investigator would preclude enrolment.
- Diagnosed blood clotting disorder
- Any genital tract procedure (e.g. biopsy) within the past 6 months
- Use of oral probiotic supplement, oral antibiotics or oral steroids within the past 30 days
- Current use of any vaginal products (except tampons) such as spermicides, microbicides, douching or drying products, antifungals, or steroids.
- Known intolerance of Lactobacillus-containing probiotic supplements
- Undiagnosed abnormal genital bleeding
- Known, suspected, or history of breast cancer
- Known or suspected estrogen-dependent malignant neoplasia (e.g. endometrial cancer)
- Currently taking immunosuppressive drugs
- Known or suspected hypersensitivity to any component of the Estring or RepHresh Pro-B products
- Diagnosis of endometrial hyperplasia
- Known liver dysfunction or disease; as long as liver function tests have failed to return to normal
- Active or past history of arterial thromboembolic disease (e.g. stroke, myocardial infarction, coronary heart disease)
- Partial or complete loss of vision due to ophthalmic vascular disease
- Porphyria
- Concomitant medication which in the opinion of the investigator may be associated with a significant drug interaction with the estrogen in Estring.
- The conditions below are grounds for exclusion based on the opinion of the investigator:
- Risk factors for estrogen dependent tumours, e.g. first degree heredity for breast cancer
- Diabetes mellitus with or without vascular involvement
- Migraine or (severe) headache
- Epilepsy
- A history of, or risk factors for, thromboembolic disorders
- Systemic lupus erythematosus
- Otosclerosis
- Cholelithiasis
- Leiomyoma (uterine fibroids)
- Endometriosis
- A history of endometrial hyperplasia
- Hypertension
- Asthma
- Diagnosed anemia
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Improving Vaginal Health to Decrease Biological Risk of HIV-1 Infection in Canadian African, Caribbean and Black (ACB) Women: Estrogen and Probiotic Treatment for Vaginal Health
This study will enrol African, Caribbean and Black (ACB) women who are known to have a more diverse vaginal microbiome, higher rates of bacterial vaginosis with lower numbers of protective lactobacilli, and are at increased risk for HIV. The investigators will evaluate the safety, feasibility, effect on the vaginal bacterial microbiome and changes in local immune and inflammatory responses with the administration of vaginal estrogen alone, vaginal estrogen in combination with oral or vaginally administered probiotics, or vaginal probiotics alone.
Read the detailed description
Women are at increased risk of HIV acquisition compared with men. A number of biological factors are associated with increased risk, many of which likely enhance risk by increasing inflammation in the female genital tract. Susceptibility to infections and immune responses in the female genital tract are regulated by hormones: progesterone increases inflammation and HIV susceptibility and estrogen decreases inflammation and enhances colonization with Lactobacilli.
A Lactobacillus dominant vaginal microbiome is associated with increased protection against HIV, while a polymicrobial vaginal flora, as seen in bacterial vaginosis, is associated with increased risk. About 40% of ACB women have a polymicrobial flora.
The goal of this study is to establish a Lactobacillus dominant vaginal microbiome in ACB women, that will be associated with decreased inflammation and decreased susceptibility to HIV, by administering a low level of intravaginal estrogen to increase colonization with Lactobacilli together with a Lactobacillus-containing probiotic.
- Conditions
- HIV-1-infection, Bacterial Vaginoses
- Being tested
- Estring Vaginal Ring, RepHresh Pro-B
- Medical subject headings
- Vaginosis, Bacterial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Estring Vaginal RingDrug
Also called 17 beta-estradiol
Estradiol vaginal ring, containing 2mg estradiol designed for slow release over 30 days
RepHresh Pro-BOther
Probiotic supplement containing 2.5 billion CFU of Lactobacilli reuteri RC-14 and Lactobacilli rhamnosus GR-1, administered vaginally or orally
| Study group | Role | What they receive |
|---|---|---|
| Estring alone | Active comparator | Participants will be given a single packet containing one Estring vaginal ring. Participants will begin using the vaginal ring on day 0 and keep it in place until day 30. Estring should not be removed during the one-month study intervention. Receives: Drug: Estring Vaginal Ring |
| Estring and vaginal RepHresh Pro-B | Active comparator | Participants will be given a single packet containing one Estring vaginal ring. Participants will begin using the vaginal ring on day 0 and keep it in place until day 30. Estring should not be removed during the one-month study intervention. Participants will also be instructed to insert one RepHresh Pro-B capsule vaginally twice daily, morning and night, until day 30 Receives: Drug: Estring Vaginal Ring; Other: RepHresh Pro-B |
| Estring and oral RepHresh Pro-B | Active comparator | Participants will be given a single packet containing one Estring vaginal ring. Participants will begin using the vaginal ring on day 0 and keep it in place until day 30. Estring should not be removed during the one-month study intervention. Participants will be instructed to take one RepHresh Pro-B capsule orally twice daily until day 30. Receives: Drug: Estring Vaginal Ring; Other: RepHresh Pro-B |
| Vaginal RepHresh Pro-B | Active comparator | Participants will be given a 30 days supply of RepHresh Pro-B and instructed to insert one capsule vaginally twice daily until day 30. Receives: Other: RepHresh Pro-B |
What is being measured
The primary outcome is the main question the study is designed to answer.
Refusal rate
Number of eligible participants approached who do not consent to be enrolled
Measured: 12 months
Participant retention rate
Number of participants who complete the study as proportion of total number of participants enrolled
Measured: 12 months
Incidence of treatment emergent adverse events
The incidence of adverse events, including serious adverse events, their severity and their relationship to study intervention assessed by reviewing case report forms and participant diaries.
Measured: 2 months
Rate of adherence
Adherence will be measured by calculating the total probiotic used/total dispensed and for Estring by total days used/total time period
Measured: 30 days
Secondary outcomes (3)
Changes in proportion of Lactobacillus species in the vaginal microbiota
Aliquots of cervico-vaginal lavage (CVL) fluids will undergo microbiome analysis using a modified Illumina sequencing method for bacterial community profiling of 16S rRNA to measure changes from baseline at follow-up sampling.
Measured: 30 days
Change in innate inflammatory cytokine/chemokine levels
Changes from baseline in levels of cytokine/chemokines will be measured in CVL by a 22-plex multiplex assay at 2 and 4 weeks
Measured: 30 days
Changes in number of HIV target cells in the genital tract
Changes from baseline in level of HIV susceptible CD4+ T cells will be quantified using a lab developed HIV pseudovirus assay at 2 and 4 weeks.
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2019
- Study start4 Nov 2019
- Primary completion14 Dec 2021
- Study completion14 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV-1-infectionStudies of the same condition, open and under way.
- More trials run by McMaster UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Collaborators
- CIHR Canadian HIV Trials Network
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03837015
- Sponsor's protocol ID
- CTN308
- Status last verified
- Dec 2021
- First submitted
- 8 Feb 2019
- Last updated
- 17 Dec 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gill B, Wessels JM, Hayes CL, Ratcliffe J, Wokuri J, Ball E, Reid G, Kaul R, Rana J, Alkhaifi M, Tharao W, Smaill F, Kaushic C. Feasibility, safety and tolerability of estrogen and/or probiotics for improving vaginal health in Canadian African, Caribbean, and Black women: A pilot phase 1 clinical trial. PLoS One. 2025 Jan 21;20(1):e0315576. doi: 10.1371/journal.pone.0315576. eCollection 2025.
PubMed 39836666
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving Vaginal Health to Decrease Biological Risk of HIV-1 Infection in Canadian African, Caribbean and Black (ACB) Women: Estrogen and Probiotic Treatment for Vaginal Health
- ClinicalTrials.gov ID
- NCT03837015
- Acronym / sponsor ID
- CTN308
- Conditions
- HIV-1-infection, Bacterial Vaginoses
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Collaborators
- CIHR Canadian HIV Trials Network
- Study start
- 4 Nov 2019 (actual)
- Primary completion
- 14 Dec 2021 (actual)
- Study completion
- 14 Dec 2021 (actual)
- First posted
- 11 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will enrol African, Caribbean and Black (ACB) women who are known to have a more diverse vaginal microbiome, higher rates of bacterial vaginosis with lower numbers of protective lactobacilli, and are at increased risk for HIV. The investigators will evaluate the safety, feasibility, effect on the vaginal bacterial microbiome and changes in local immune and inflammatory responses with the administration of vaginal estrogen alone, vaginal estrogen in combination with oral or vaginally administered probiotics, or vaginal probiotics alone.
Detailed description
Women are at increased risk of HIV acquisition compared with men. A number of biological factors are associated with increased risk, many of which likely enhance risk by increasing inflammation in the female genital tract. Susceptibility to infections and immune responses in the female genital tract are regulated by hormones: progesterone increases inflammation and HIV susceptibility and estrogen decreases inflammation and enhances colonization with Lactobacilli.
A Lactobacillus dominant vaginal microbiome is associated with increased protection against HIV, while a polymicrobial vaginal flora, as seen in bacterial vaginosis, is associated with increased risk. About 40% of ACB women have a polymicrobial flora.
The goal of this study is to establish a Lactobacillus dominant vaginal microbiome in ACB women, that will be associated with decreased inflammation and decreased susceptibility to HIV, by administering a low level of intravaginal estrogen to increase colonization with Lactobacilli together with a Lactobacillus-containing probiotic.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Estring alone | Active comparator | Drug: Estring Vaginal RingParticipants will be given a single packet containing one Estring vaginal ring. Participants will begin using the vaginal ring on day 0 and keep it in place until day 30. Estring should not be removed during the one-month study intervention. |
| Estring and vaginal RepHresh Pro-B | Active comparator | Drug: Estring Vaginal Ring, Other: RepHresh Pro-BParticipants will be given a single packet containing one Estring vaginal ring. Participants will begin using the vaginal ring on day 0 and keep it in place until day 30. Estring should not be removed during the one-month study intervention. Participants will also be instructed to insert one RepHresh Pro-B capsule vaginally twice daily, morning and night, until day 30 |
| Estring and oral RepHresh Pro-B | Active comparator | Drug: Estring Vaginal Ring, Other: RepHresh Pro-BParticipants will be given a single packet containing one Estring vaginal ring. Participants will begin using the vaginal ring on day 0 and keep it in place until day 30. Estring should not be removed during the one-month study intervention. Participants will be instructed to take one RepHresh Pro-B capsule orally twice daily until day 30. |
| Vaginal RepHresh Pro-B | Active comparator | Other: RepHresh Pro-BParticipants will be given a 30 days supply of RepHresh Pro-B and instructed to insert one capsule vaginally twice daily until day 30. |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- African, Caribbean, Black
- Pre-menopausal women in good general health, as determined by the investigator
- Uterus and cervix present
- Negative pregnancy test
- Currently practicing barrier or non-hormonal forms of contraception, and planning to continue, for the duration of the study (barrier contraceptive, abstinence)
Key exclusion criteria (42 listed)
- Currently lactating
- Pregnant: suspected, current or in the last 12 months
- Irregular menstrual cycle (less than 6 periods in a year) not related to contraceptive use, pregnancy or breastfeeding
- Post-menopausal
- Hormonal Contraceptive use or other hormonal treatment in the past 3 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Estring Vaginal RingAlso: 17 beta-estradiolEstradiol vaginal ring, containing 2mg estradiol designed for slow release over 30 days | Drug | Estring alone, Estring and oral RepHresh Pro-B, Estring and vaginal RepHresh Pro-B |
| RepHresh Pro-BProbiotic supplement containing 2.5 billion CFU of Lactobacilli reuteri RC-14 and Lactobacilli rhamnosus GR-1, administered vaginally or orally | Other | Estring and oral RepHresh Pro-B, Estring and vaginal RepHresh Pro-B, Vaginal RepHresh Pro-B |
Primary outcome
Refusal rate
Time frame: 12 months
Number of eligible participants approached who do not consent to be enrolled
Participant retention rate
Time frame: 12 months
Number of participants who complete the study as proportion of total number of participants enrolled
Incidence of treatment emergent adverse events
Time frame: 2 months
The incidence of adverse events, including serious adverse events, their severity and their relationship to study intervention assessed by reviewing case report forms and participant diaries.
Rate of adherence
Time frame: 30 days
Adherence will be measured by calculating the total probiotic used/total dispensed and for Estring by total days used/total time period
3 secondary outcomes
Changes in proportion of Lactobacillus species in the vaginal microbiota
Time frame: 30 days
Change in innate inflammatory cytokine/chemokine levels
Time frame: 30 days
Changes in number of HIV target cells in the genital tract
Time frame: 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2021.
- Derived from this study: PubMed 39836666Gill B, Wessels JM, Hayes CL, Ratcliffe J, Wokuri J, Ball E, Reid G, Kaul R, Rana J, Alkhaifi M, Tharao W, Smaill F, Kaushic C. Feasibility, safety and tolerability of estrogen and/or probiotics for improving vaginal health in Canadian African, Caribbean, and Black women: A pilot phase 1 clinical trial. PLoS One. 2025 Jan 21;20(1):e0315576. doi: 10.1371/journal.pone.0315576. eCollection 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Estring Vaginal Ring and RepHresh Pro-B in people with HIV-1-infection and Bacterial Vaginoses, run by McMaster University at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Refusal rate (time frame: 12 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03837015, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2021.