Influence of Reproductive Cycle and Menopause on HIV-1 Infection and TFV Gel Activity

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by CONRAD
Sponsor:
Information provided by (Responsible Party):
CONRAD
ClinicalTrials.gov Identifier:
NCT01810315
First received: March 11, 2013
Last updated: April 11, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
HIV Prevention
Drug: TFV 1% gel
Drug: Estradiol vaginal cream
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: Influence of Female Reproductive Cycle and Menopause on Cervicovaginal Tissue Susceptibility to HIV-1 Infections and Tenofovir 1% Gel Activity

Resource links provided by NLM:


Further study details as provided by CONRAD:

Primary Outcome Measures:
  • Concentrations of tenofovir in plasma, vaginal aspirate, and genital tissue [ Time Frame: 3 hours after dosing ] [ Designated as safety issue: No ]
  • Concentrations of TFV-DP in genital tissue [ Time Frame: 3 hours after dosing ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: September 2013
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Baseline
Premenopausal women will undergo baseline sampling in each the follicular and luteal phase. Postmenopausal women will undergo baseline sampling one time.
Experimental: TFV 1% Gel

Participants will vaginally insert 1 applicator of TFV gel followed by a 2nd applicator 2 hours later. Each applicator contains 4.4 gm of TFV 1% gel.

Premenopausal women will undergo sampling after TFV gel use in each the follicular and luteal phase. Postmenopausal women will undergo sampling after TFV gel use one time.

Drug: TFV 1% gel
Experimental: Estradiol Vaginal Cream
Post menopausal women only: Participants will insert 2 grams of estradiol cream into the vagina every night for 14 days and then one gram of estradiol cream into the vagina every other night
Drug: Estradiol vaginal cream
Experimental: TFV 1% gel and estradiol cream
Postmenopausal women only: Participants will vaginally insert 1 applicator of TFV gel followed by a 2nd applicator 2 hours later. Each applicator contains 4.4 gm of TFV 1% gel. In addition, participants will one gram of estradiol cream into the vagina every other night.
Drug: TFV 1% gel Drug: Estradiol vaginal cream

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

Ages Eligible for Study:   21 Years to 89 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01810315

Locations
United States, Virginia
Clinical Research Center, Eastern Virginia Medical School Recruiting
Norfolk, Virginia, United States, 23507
Contact: Cooper    757-446-8487      
Principal Investigator: Andrea Thurman, MD         
Sponsors and Collaborators
CONRAD
  More Information

No publications provided

Responsible Party: CONRAD
ClinicalTrials.gov Identifier: NCT01810315     History of Changes
Other Study ID Numbers: A12-124
Study First Received: March 11, 2013
Last Updated: April 11, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Estradiol
Polyestradiol phosphate
Estradiol valerate
Estradiol 17 beta-cypionate
Estradiol 3-benzoate
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Contraceptive Agents
Reproductive Control Agents
Therapeutic Uses
Contraceptive Agents, Female

ClinicalTrials.gov processed this record on September 30, 2014