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

• Status: Recruiting
• Trial end date: 2022-03-31
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: McMaster University
• Collaborator: CIHR Canadian HIV Trials Network
• Treatments: Estradiol; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Estradiol valerate; Estrogens; Polyestradiol phosphate; Probenecid

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

• 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:

1. Risk factors for estrogen dependent tumours, e.g. first degree heredity for breast cancer

2. Diabetes mellitus with or without vascular involvement

3. Migraine or (severe) headache

4. Epilepsy

5. A history of, or risk factors for, thromboembolic disorders

6. Systemic lupus erythematosus

7. Otosclerosis

8. Cholelithiasis

9. Leiomyoma (uterine fibroids)

10. Endometriosis

11. A history of endometrial hyperplasia

12. Hypertension

13. Asthma

14. Diagnosed anemia