Clinical trial NCT01810315: Influence of Reproductive Cycle and Menopause on HIV-1 Infection and TFV Gel Activity
Official title: Influence of Female Reproductive Cycle and Menopause on Cervicovaginal Tissue Susceptibility to HIV-1 Infections and Tenofovir 1% Gel Activity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Prevention
Lead sponsor: CONRAD
Sponsor class: OTHER
First posted: 2013-03-13
Enrollment: 40
Sex: FEMALE
Minimum age (years): 21
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER

Brief summary: Purpose of the study is to assess tenofovir (TFV) PK and PD endpoints, cervicovaginal safety parameters, susceptibility to HIV-1 infection, and objective measures of vaginal applicator use in premenopausal and postmenopausal women.

Detailed description: Premenopausal women: Baseline blood and genital samples will be taken in the follicular and luteal phase (visits 2 and 3). The participant will be given TFV gel and instructed to insert two doses, separated by 2 hours, and return to the clinic 3 hours after the second insertion for blood and genital samples (visits 4/4a and 5/5a).

Postmenopausal women: Premenopausal women: Baseline blood and genital samples will be taken (visit 2). The participant will be given TFV gel and instructed to insert two doses, separated by 2 hours, and return to the clinic 3 hours after the second insertion for blood and genital samples (visit 3/3a). Estradiol cream will be distributed at visit 4. Post estradiol blood and genital samples will be taken at Visit 5. The participant will given TFV gel and instructed to insert 2 doses as before, while continuing to use the estradiol cream. Post TFV gel and estradiol cream blood and genital samples will be taken (visit 6/6a).

Eligibility criteria: Inclusion Criteria: All volunteers

* In good healthsignificant systemic disease
* Not at risk of an STI, meaning: In a monogamous heterosexual or same sex relationship for at least the last four months with a partner who is not known to be HIV positive and has no known risks for STIs OR sexually abstinent
* Willing and able to comply with study procedures
* Normal Pap smear (by written report) in the past year.

Inclusion Criteria: Premenopausal volunteers

* 21-to-45 years of age
* Not at risk for pregnancy, meaning:
* Regular menstrual cycles (every 24 - 35 days)
* Luteal phase P level of greater than or equal to 3 ng/ml

Inclusion Criteria: Postmenopausal volunteers

* 46-89 years of age OR both ovaries removed at least 30 days prior to Visit 1
* No menstrual periods/vaginal bleeding in the past 12 months OR both ovaries removed at least 30 days prior to Visit 1
* FSH level of greater than or equal to 20 MIU/ml

Exclusion Criteria: All volunteers

* Clinically significant history of an abnormal Pap smear in the past year
* Surgery or biopsy of the vagina or cervix within 30 days
* Current STI or lower genital tract infection
* Current use of chronic immunosuppressants
* Current presence of vulvar, anal and/or vaginal genital warts
* Current tobacco use of any amount
* History of sensitivity/allergy to any component of the study product, topical anesthetic, or allergy to silver nitrate and/or Monsel's solution
* Known bleeding disorder that could lead to prolonged or continuous bleeding
* Grade 1 or higher laboratory abnormality, per the August 2009 update of the DAIDS Table for Grading the Severity of Adverse Events
* Systemic use in the last two weeks or anticipated use during the study of any of the following: corticosteroids, antibiotics, anticoagulants or other drugs known to prolong bleeding and/or clotting, antifungals, antivirals or antiretrovirals.
* Investigator discretion
* Current participation in any other drug or device study

Exclusion Criteria: Premenopausal women

* Use of DMPA in last six months
* Use of any other hormonal contraceptive method without 2 subsequent, normal menses since stopping hormonal contraceptives
* Current use of copper IUD
* Currently pregnant or pregnancy within the past 3 months
* Currently breastfeeding/having breastfed an infant in the last 2 months

Exclusion Criteria: Postmenopausal women

* Use of any hormonal medications in the past 30 days
* Contraindications to vaginal estrogen cream

Primary outcomes:
measure: Concentrations of tenofovir in plasma, vaginal aspirate, and genital tissue
timeFrame: 3 hours after dosing
measure: Concentrations of TFV-DP in genital tissue
timeFrame: 3 hours after dosing
Secondary outcomes:
Other outcomes:
Locations:
city: Norfolk
country: United States
facility: Clinical Research Center, Eastern Virginia Medical School
state: Virginia
Study officials:
References: