Estrogen, Probiotics and Vaginal Health to Prevent HIV Infection in ACB Women

NCT03837015 | Completed Phase 1 DMC

• 1 other identifier: CTN308
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

HIV-1-infection; Bacterial Vaginoses

Outcome Measures

Primary Outcomes (4)

• Refusal rate

  Number of eligible participants approached who do not consent to be enrolled

  12 months

• Participant retention rate

  Number of participants who complete the study as proportion of total number of participants enrolled

  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.

  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

  30 days

Secondary Outcomes (3)

• Changes in proportion of Lactobacillus species in the vaginal microbiota

  30 days

• Change in innate inflammatory cytokine/chemokine levels

  30 days

• Changes in number of HIV target cells in the genital tract

  30 days

Study Arms (4)

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.

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

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.

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.

Other: RepHresh Pro-B

Interventions

Estring Vaginal Ring DRUG

Estradiol vaginal ring, containing 2mg estradiol designed for slow release over 30 days

Also known as: 17 beta-estradiol

Estring alone; Estring and oral RepHresh Pro-B; Estring and vaginal RepHresh Pro-B

RepHresh Pro-B OTHER

Probiotic supplement containing 2.5 billion CFU of Lactobacilli reuteri RC-14 and Lactobacilli rhamnosus GR-1, administered vaginally or orally

Estring and oral RepHresh Pro-B; Estring and vaginal RepHresh Pro-B; Vaginal RepHresh Pro-B

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• McMaster University: lead
• CIHR Canadian HIV Trials Network: collaborator

Study Sites (1)

Women's Health in Women's Hands

Toronto, Ontario, M5B1J3, Canada

Location

Related Publications (1)

• 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.

  PMID: 39836666 DERIVED

MeSH Terms

Conditions

Vaginosis, Bacterial

Interventions

Estradiol

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Vaginitis; Vaginal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2019
• First Posted: February 11, 2019
• Study Start: November 4, 2019
• Primary Completion: December 14, 2021
• Study Completion: December 14, 2021
• Last Updated: December 17, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)