Clinical Trial on the Effects of Progestin-based Contraception in the Genital Tract of HIV-infected and Uninfected Women

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Centers for Disease Control and Prevention
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:
NCT02103660
First received: April 1, 2014
Last updated: April 22, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to determine the acceptability of randomization to contraceptive options and estimate the effect of progestin contraception on HIV genital shedding and inflammatory/immune perturbations in women who may or may not be on antiretroviral therapy, as well as in HIV-uninfected women controls. It is hypothesized that progestin-containing contraception will lead to inflammatory changes that may affect the local immune activity, influencing HIV acquisition or transmissibility risk.


Condition Intervention Phase
HIV
Contraception
Drug: Depo-Medroxyprogesterone Acetate
Drug: Progestin Contraceptive (Jadelle)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: A Randomized Clinical Trial on the Effects of Progestin-based Contraception in the Genital Tract of HIV-infected and Uninfected Women

Resource links provided by NLM:


Further study details as provided by Centers for Disease Control and Prevention:

Primary Outcome Measures:
  • HIV viral load in the genital tract of HIV-infected women before and after initiation of progestin-containing contraception [ Time Frame: 6 months post randomization ] [ Designated as safety issue: Yes ]
    Genital HIV viral load at each study visit will be modeled longitudinally as a continuous outcome using a generalized estimating equation (GEE) model. The model will include a covariate indicating whether the measurement was taken before or after receiving the contraceptive method, and the null hypothesis will be tested using a z-test on this covariate.

  • HIV viral load in the genital tract of HIV-infected women by contraceptive type [ Time Frame: 6 months post randomization ] [ Designated as safety issue: Yes ]
    Genital HIV viral load at each study visit will be modeled longitudinally as a continuous outcome using a generalized estimating equation (GEE) model. The model will include a covariate for contraception arm, and the null hypothesis will be tested using a z-test on this covariate.


Secondary Outcome Measures:
  • Impact of the type of progestin-containing contraception (injectable versus implant) on inflammatory/immune markers in the genital tract women. [ Time Frame: 6 months post randomization ] [ Designated as safety issue: Yes ]
    A series of paired t-tests or Wilcoxon signed-rank tests, with Bonferonni correction, will be used for the within-subject assessments of all the immune markers, before and after contraceptive initiation. The baseline value will be the mean of the follicular and luteal phase values, and it will be compared to the value for each study time point after contraceptive initiation. Comparisons will be performed between subjects in the LNG-implant and DMPA arms.

  • Contraceptive efficacy in HIV-infected women [ Time Frame: 6 months post randomization ] [ Designated as safety issue: Yes ]
    Contraceptive efficacy will be measured by the occurrence of any pregnancies and compared by antiretroviral status

  • Interaction of progesting-based hormonal contraception and antiretroviral therapy [ Time Frame: 6 months post randomization ] [ Designated as safety issue: Yes ]
    Plasma and female genital tract ARV drug concentrations will be expressed as geometric mean with corresponding 95% CI. Correlation between genital tract viral shedding, plasma and genital tract ARV concentrations and HC will be assessed with longitudinal models using GEE. Outcomes will be compared between the DMPA and the implant users evaluating the contraceptive method as an effect modifier for HIV shedding or ART concentrations within the longitudinal models.


Estimated Enrollment: 130
Study Start Date: April 2014
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Depo-Medroxyprogesterone Acetate
Half of women will be randomized to receive Depo-Medroxyprogesterone Acetate injections every 13 weeks
Drug: Depo-Medroxyprogesterone Acetate
150 mg Depo-Medroxyprogesterone Acetate administered every 13 weeks
Other Names:
  • Depo provera
  • DMPA
  • injectable contraception
Active Comparator: Progestin Implant (Jadelle)
Half of women will be randomized to receive progestin implant.
Drug: Progestin Contraceptive (Jadelle)
2 implants containing 75 mg of levonorgestrel will be implanted and will last for up to 5 years
Other Names:
  • Jadelle
  • Contraceptive Implant

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Known HIV status, as documented by at least 2 positive rapid tests (Determine and Uni-Gold, respectively). If the 2 rapid tests are discordant, then a confirmatory test will be done via Western blot.
  • Female, pre-menopausal, age 18 to 45 years
  • At least 2 regular, monthly cycles (~21-35 days) in the 3 months preceding study enrollment.
  • If on hormonal or intrauterine contraception in the past, they must have been off for at least 6 months. If they were previously using DMPA, their last -injection must have been ≥6 months ago.
  • If recently pregnant, they must be at least 6 months postpartum
  • Able and willing to provide informed consent
  • Be otherwise a good candidate for study participation based on assessment by investigator or designee
  • Interested in initiating a family planning method, specifically depot medroxyprogesterone acetate (DMPA) or the LNG implant (Jadelle)
  • Willing to be randomized to receive either DMPA or LNG implant (Jadelle)
  • Willing to wait 4-6 weeks after enrollment to receive this method and to use non-hormonal and non-intrauterine methods (such as abstinence or condoms) consistently during this period

Exclusion Criteria:

  • Pregnancy (by clinical history or a positive urine pregnancy test at screening)
  • Women currently using any hormonal contraceptive method
  • Desire pregnancy within next 12 months
  • Untreated visible genital ulcers or lesions on initial pelvic examination
  • Known or suspected genital tract cancer (by clinical history or noted during initial pelvic examination).
  • Contraindications to DMPA or LNG implant per the WHO medical eligibility114 criteria or judgment of clinician (contraindications include lactation within first 6 weeks postpartum, acute deep venous thrombosis or pulmonary embolism, lupus, migraine with aura, unexplained vaginal bleeding, current or history of breast cancer, severe cirrhosis, liver tumors, history of stroke, current or history of ischemic heart disease).
  • Acute HIV infection (as documented by a known negative HIV test 6 months or less prior to screening).
  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: NCT02103660

Contacts
Contact: Jennifer Tang, MD, MSCR +265-99-640-2662 jennifer_tang@med.unc.edu

Locations
Malawi
UNC-Project Lilongwe Recruiting
Lilongwe, Malawi
Principal Investigator: Lameck Chinula, MD         
Sponsors and Collaborators
Investigators
Study Chair: Charles M van der Horst, MD University of North Carolina
  More Information

No publications provided

Responsible Party: Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier: NCT02103660     History of Changes
Other Study ID Numbers: CDC-NCCDPHP-6512, 1K01TW009657-01, U48-DP-001944, SIP 09-022
Study First Received: April 1, 2014
Last Updated: April 22, 2014
Health Authority: United States: Federal Government
Malawi: National Health Sciences Research Committee

Keywords provided by Centers for Disease Control and Prevention:
contraceptive implant
Depo-Medroxyprogesterone Acetate
Hormonal Contraception
progestin

Additional relevant MeSH terms:
Contraceptive Agents
Levonorgestrel
Medroxyprogesterone
Medroxyprogesterone Acetate
Progestins
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Contraceptive Agents, Female
Contraceptive Agents, Male
Contraceptives, Oral
Contraceptives, Oral, Synthetic
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014