Hypoestrogenism Clinical Trial
Official title:
Impact of Concurrent Initiation of DMPA Contraception and Tenofovir PrEP on Bone Loss in Young Women
Verified date | June 2024 |
Source | University of Washington |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The primary objective of this study is to address critical safety questions with concurrent TDF-based PrEP and DMPA use. We hypothesize that young women using TDF-based PrEP and DMPA will have lower bone acquisition and altered bone metabolism. Bone mineral metabolism is in part regulated by the kidney, and we hypothesize that bone effects from concurrent PrEP and DMPA use will be driven by subclinical kidney injury, a known side effect of TDF, as well as DMPA-induced hypoestrogenism. To investigate our hypothesis, we will enroll a prospective cohort of approximately 500 HIV-uninfected women ages 16-25 years in Kampala, Uganda who have substantial HIV risk and are initiating DMPA or barrier method contraception. Over a 24-month period, we will offer TDF-based PrEP. We will use state-of-the-art radiologic, biochemical, and epidemiologic methods to test the hypothesis that concurrent TDF-based PrEP and DMPA use results in compounding adverse effects on bone health.
Status | Completed |
Enrollment | 500 |
Est. completion date | December 21, 2023 |
Est. primary completion date | December 21, 2023 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Female |
Age group | 16 Years to 25 Years |
Eligibility | Inclusion Criteria: - Inclusion criteria: - Age 16-25 If age 16-17: - qualification as an emancipated minor (due to past pregnancy, being married, having a child, or catering for their own livelihood) or a mature minor (due to having a sexually transmitted infection) or able to have a parent/guardian provide informed consent - HIV-uninfected - Initiated DMPA within the past 90 days or using condoms only for contraception - Willing and able to provide written informed consent - Not planning to get pregnant in the next 24 months - Sexually active - Planning to remain in the study area for the next 2 years Exclusion Criteria: - Exclusion criteria: - Currently enrolled in a biomedical HIV-1 prevention study - Current or prior use of PrEP consecutively in the last 3 months - Abnormal renal function (creatinine clearance <60 min/ml) - Hepatitis B infection - Currently pregnant or breastfeeding - Current DMPA use for longer than 90 days - Use of implant, IUD, or oral contraceptives - Past hysterectomy, oophorectomy, or tubal ligation - Current or recent history of primary or secondary amenorrhea - Taking medications known to interfere with bone metabolism (steroids, anti-convulsants, bisphosphonates, cancer drugs). - Has any other condition that would preclude the ability to provide informed consent, make study participation unsafe, complicate the interpretation of study findings or otherwise interfere with achievement of the study objectives, in the investigator's discretion. |
Country | Name | City | State |
---|---|---|---|
Uganda | Infectious Disease Institute | Kampala |
Lead Sponsor | Collaborator |
---|---|
University of Washington | Columbia University, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Icahn School of Medicine at Mount Sinai, Makerere University, MU-JHU CARE |
Uganda,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | The investigators will assess whether young women using TDF-based PrEP and DMPA concurrently attain lower peak bone mass over a 24-month relative to women using either agent singly or neither agent. | The investigators will use dual energy x-ray absorptiometry (DXA) scans to measure BMD annually at 3 anatomical sites (lumbar spine, total hip, and wrist).
Hypothesis: Relative to women using DMPA only (without tenofovir exposure) and women using PrEP only (without DMPA exposure), women concurrently using TDF-based PrEP and DMPA will have lower bone mass. |
24 months | |
Primary | The investigators will assess whether young women using TDF-based PrEP and DMPA concurrently have evidence of disrupted microarchitecture, relative to women using either agent singly or neither agent. | The investigators will use dual energy x-ray absorptiometry (DXA) scans to derive the trabecular bone score (TBS), an index of lumbar spine trabecular microarchitecture.
Hypothesis: Relative to women using DMPA only (without tenofovir exposure) and women using PrEP only (without DMPA exposure), women concurrently using TDF-based PrEP and DMPA will have more disruptions in bone microarchitecture. |
24 months | |
Secondary | The investigators will investigate whether young women concurrently using TDF-based PrEP and DMPA experience higher rates of bone turnover. | At baseline and 24 months, the investigators will measure:
Markers of bone formation and resorption (e.g. NTX, P1NP, serum intact parathyroid hormone, total and bioavailable 25-OH-vitamin D). Hypothesis: Relative to women using DMPA only and PrEP only, women concurrently using TDF-based PrEP and DMPA will have increased bone turnover markers and PTH. |
Change from Baseline at 24 months | |
Secondary | The investigators will investigate whether young women concurrently using TDF-based PrEP and DMPA experience higher rates of subclinical kidney injury. | At baseline and 24 months, the investigators will measure: Markers of kidney function (phosphate, glucose, creatinine, total protein, albumin).
Hypothesis: Relative to women using DMPA only and PrEP only, women concurrently using TDF-based PrEP and DMPA will have more frequent subclinical kidney injury (relative to women without tenofovir exposure) |
Change from Baseline at 24 months | |
Secondary | The investigators will investigate whether young women concurrently using TDF-based PrEP and DMPA experience higher rates of hypoestrogenism. | At baseline and 24 months, the investigators will measure: Markers of estrogen (serum estradiol, sex hormone binding protein, and the occurrence of amenorrhea).
Hypothesis: Relative to women using DMPA only and PrEP only, women concurrently using TDF-based PrEP and DMPA will have reduced serum estrogen (relative to women without DMPA exposure). |
Change from Baseline at 24 months | |
Secondary | Using mediation analysis, the investigators will identify the degree to which the pathways through subclinical kidney injury and hypoestrogenism account for changes in bone density among women concurrently using TDF-based PrEP and DMPA | The investigators will conduct mediation analysis to determine the degree to which changes in the pathways through subclinical kidney injury, hypoestrogenism and the combination of these pathways account for changes in bone density.
Hypothesis: The pathway through hypoestrogenism will be a stronger link between concurrent TDF-based PrEP and DMPA use and bone density changes. |
24 months |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05704036 -
Estrogen Supplementation and Bone Health in Women With CF
|
Phase 4 | |
Completed |
NCT04336891 -
Effect of Testosterone Treatment on Clitoral Arteries' Hemodynamic Parameters.
|
||
Recruiting |
NCT06136208 -
Pharmacokinetic Aspects of 25-mg Estradiol Pellet in Climacteric Women
|
N/A | |
Recruiting |
NCT06353269 -
Adherence to Vaginal Estrogen Therapy in Hypoestrogenic Women With Recurrent Urinary Tract Infections
|
Phase 4 |