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Trial record 8 of 76 for:    "Bacterial Infectious Disease" | "Polyestradiol phosphate"

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

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ClinicalTrials.gov Identifier: NCT03837015
Recruitment Status : Not yet recruiting
First Posted : February 11, 2019
Last Update Posted : June 5, 2019
Sponsor:
Collaborator:
CIHR Canadian HIV Trials Network
Information provided by (Responsible Party):
McMaster University

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.

Condition or disease Intervention/treatment Phase
HIV-1-infection Bacterial Vaginoses Drug: Estring Vaginal Ring Other: RepHresh Pro-B Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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
Estimated Study Start Date : July 2019
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : April 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Active Comparator: Estring alone
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
Estradiol vaginal ring, containing 2mg estradiol designed for slow release over 30 days
Other Name: 17 beta-estradiol

Active Comparator: Estring and vaginal RepHresh Pro-B
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
Estradiol vaginal ring, containing 2mg estradiol designed for slow release over 30 days
Other Name: 17 beta-estradiol

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

Active Comparator: Estring and oral RepHresh Pro-B
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
Estradiol vaginal ring, containing 2mg estradiol designed for slow release over 30 days
Other Name: 17 beta-estradiol

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

Active Comparator: Vaginal RepHresh Pro-B
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
Probiotic supplement containing 2.5 billion CFU of Lactobacilli reuteri RC-14 and Lactobacilli rhamnosus GR-1, administered vaginally or orally




Primary Outcome Measures :
  1. Refusal rate [ Time Frame: 12 months ]
    Number of eligible participants approached who do not consent to be enrolled

  2. Participant retention rate [ Time Frame: 12 months ]
    Number of participants who complete the study as proportion of total number of participants enrolled

  3. 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.

  4. 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


Secondary Outcome Measures :
  1. Changes in proportion of Lactobacillus species in the vaginal microbiota [ Time Frame: 30 days ]
    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.

  2. Change in innate inflammatory cytokine/chemokine levels [ Time Frame: 30 days ]
    Changes from baseline in levels of cytokine/chemokines will be measured in CVL by a 22-plex multiplex assay at 2 and 4 weeks

  3. Changes in number of HIV target cells in the genital tract [ Time Frame: 30 days ]
    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.



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Ages Eligible for Study:   18 Years to 49 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03837015


Contacts
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Contact: Charu Kaushic, PhD 905-525-9140 ext 22988 kaushic@mcmaster.ca
Contact: Fiona Smaill, MB,ChB 905-521-2100 ext 74190 smaill@mcmaster.ca

Sponsors and Collaborators
McMaster University
CIHR Canadian HIV Trials Network

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Responsible Party: McMaster University
ClinicalTrials.gov Identifier: NCT03837015     History of Changes
Other Study ID Numbers: CTN308
First Posted: February 11, 2019    Key Record Dates
Last Update Posted: June 5, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Bacterial Infections
Estradiol
Polyestradiol phosphate
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Infection
Communicable Diseases
HIV Infections
Vaginosis, Bacterial
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Vaginitis
Vaginal Diseases
Genital Diseases, Female
Estrogens
Probenecid
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female
Uricosuric Agents
Gout Suppressants