Levels of Raltegravir in the Female Genital Tissue
Modeling Intracellular and Extracellular Raltegravir (RAL) Pharmacokinetics in the Female Genital Tract and Blood After a Twice Daily 400mg Dose Over the Course of a Menstrual Cycle
This study is an investigation of the pharmacokinetics of raltegravir in the tissue of the female genital tract to determine if twice-daily dosing of 400mg achieves adequate drug levels to prevent viral integration of HIV-1. The study will also assess whether drug levels change in the tissue across the different phases of the menstrual cycle.
- Hypothesis #1: Twice daily dosing with raltegravir 400mg will result in intracellular concentrations that should be sufficient to suppress HIV-1 replication throughout the menstrual cycle.
- Hypothesis #2: Intracellular genital raltegravir peaks will be lower and troughs higher compared to extracellular concentrations in the plasma and PMBCs (peripheral blood mononuclear cells).
- Hypothesis #3: Intracellular raltegravir concentrations will be slightly lower during the luteal phase of the menstrual cycle due to cellular pumps such as p-glycoprotein, which are present in higher numbers during periods of high progesterone.
연구 개요
상세 설명
HIV-1 is shed in genital secretions which increase the risk of transmission between sexual partners and from mother to infant. Antiretroviral medication taken prior to exposure to HIV-1 can prevent viral transmission from a mother to her infant. Raltegravir (RAL), by blocking integration of viral cDNA into the host's genome, makes an excellent candidate for preventing HIV-1 infection. RAL is licensed for treatment with twice-daily dosing based on plasma trough concentrations; however, intracellular concentrations of RAL which are relevant to blocking infection of cells have not been previously studied. P-glycoprotein pumps, which are involved in regulating drug absorption and metabolism, can influence intracellular drug concentrations. P-glycoprotein concentrations appear to vary with menstrual cycle suggesting it may affect intracellular drug concentration of RAL in women.
Women will be enrolled in the study and followed during the course of a menstrual cycle while taking a dose of 400mg PO twice daily. An initial screening visit will be performed prior to enrollment and participation in the study. Review of medical history as well as blood and urine collection will occur during the screening visit. Once enrolled, participants will have blood and genital tract samples collected once a week for four weeks to assess intracellular concentrations of RAL in the blood and genital tract tissue.
연구 유형
등록 (실제)
단계
- 해당 없음
연락처 및 위치
연구 장소
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Washington
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Seattle, Washington, 미국, 98195
- University of Washington, Clinical Research Center
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria
Volunteers must be:
- Over 18 years of age.
- Willing to abstain from sexual intercourse during course of study.
- Able to commit to follow-up visit schedule.
- Willing to abstain from use of vaginal medications or creams 48 hours prior to follow-up visits.
- Willing and able to provide informed consent.
Exclusion Criteria
Volunteers will not be eligible for the study if they:
- Are over 50 years of age.
- Are pregnant, attempting to become pregnant, or breast-feeding.
- Have irregular menstrual bleeding.
- Are using a hormonal form of birth control.
- Have abnormal liver/kidney function test results at screening visit.
- Have HIV-positive test result at screening visit.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: All
All patients were part of the intervention arm, as this was a pharmacokinetic study.
All women took Raltegravir 400mg orally, twice daily for 3 weeks.
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Dosage: 400mg/PO (by mouth) Frequency: Twice daily Duration: During course of menstrual cycle (28 days)
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Tissue Raltegravir Concentrations
기간: 7, 14, 21 days
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Mean trough concentration from all three days.
Tissue concentrations are measured from cervical biopsy homogenate using a mass-spectroscopy-based method.
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7, 14, 21 days
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Plasma Raltegravir Concentrations
기간: 7, 14, 21 days
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Mean trough concentration from all 3 days
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7, 14, 21 days
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공동 작업자 및 조사자
수사관
- 수석 연구원: Caroline Mitchell, MD, University Washington
- 수석 연구원: Lisa Frenkel, MD, Seattle Children's Research Institute
연구 기록 날짜
연구 주요 날짜
연구 시작
기본 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (추정)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
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