Bone DemineralizationPhase 4NCT03464266
The Kampala Women's Bone Study
A Phase 4 study testing FTC/TDF and DMPA, FTC/TDF and DMPA in people with Bone Demineralization and Hypoestrogenism, run by University of Washington at 1 site in Uganda.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 16 to 25 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Bone Demineralization, Hypoestrogenism, Subclinical Kidney Injury
- What is being tested?
- FTC/TDF and DMPA, FTC/TDF and DMPA
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 500 participants
- Where
- 1 siteUganda
- Study dates
- 15 May 2018to 21 Dec 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 25 years
- Women only
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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
Show all 9Show fewer
- Not planning to get pregnant in the next 24 months
- Sexually active
- Planning to remain in the study area for the next 2 years
Who cannot join
- 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
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Impact of Concurrent Initiation of DMPA Contraception and Tenofovir PrEP on Bone Loss in Young Women
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.
Read the detailed description
The proposed research will investigate the hypothesis that TDF-based PrEP and DMPA initiated concurrently by HIV-uninfected women will enhance each other's effects on bone metabolism. The investigators will conduct an open-label prospective study of approximately 500 HIV-uninfected women at substantial risk for HIV-infection who are newly initiating DMPA or using condoms as their only contraceptive in Kampala, Uganda. The investigators will offer PrEP to all of these women and determine the joint effect of PrEP and DMPA on changes in bone mass (Aim 1), bone turnover, subclinical kidney injury, and hypoestrogenism (Aim 2), and conduct mediation analysis to assess the contribution of each pathway to overall losses in bone mass (Aim 3).
- The investigators will assess whether young women using TDF-based PrEP and DMPA concurrently attain lower peak bone mass over a 24-month period and 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 measure BMD annually at 3 anatomical sites (lumbar spine, total hip, and wrist). Additionally, the investigators will derive the trabecular bone score (TBS), an index of lumbar spine trabecular microarchitecture.
- The investigators will investigate whether young women concurrently using TDF-based PrEP and DMPA experience: 1) higher rates of bone turnover, a direct precursor to bone loss and 2) subclinical kidney injury and hypoestrogenism, markers of two mechanistic pathways between TDF and DMPA use and bone mass
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)
- Markers of kidney function (phosphate, glucose, creatinine, total protein, albumin) and
- 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 increased bone turnover markers and PTH. In addition, women concurrently using TDF-based PrEP and DMPA will have more frequent subclinical kidney injury (relative to women without tenofovir exposure) and reduced serum estrogen (relative to women without DMPA exposure).
- 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.
Over a 24-month period, the investigators will follow women quarterly with HIV rapid testing, PrEP adherence counseling and refills, DMPA injections, and provision of other contraceptives as desired. At enrollment and quarterly visits, the investigators will assess physical activity, sexual behavior, and menstrual cycle characteristics. Annually, the investigators will conduct physical exams and anthropometric readings. Sexually transmitted infections will be routinely assessed syndromically, according to national guidelines. Women will be encouraged to consider their HIV risk and fertility desires at every visit and counseled about contraception and PrEP accordingly. Dual energy x-ray absorptiometry (DXA) scans will be performed at baseline and annually thereafter. Blood and urine samples will be obtained quarterly, aliquoted, and archived at minus 80o Celsius.
DXA and TBS assessments:
DXA scans will be conducted at study enrollment (within 1 week of contraceptive initiation), 12, and 24 months after enrollment. DXA is the clinical standard for measuring BMD. It is painless and non-invasive. Women will be exposed to a relatively low level of radiation which is <1/10 the dose of a standard chest x-ray, and less than a day's exposure to natural radiation. BMD by DXA of the hip and spine is generally considered the most reliable way to classify osteoporosis, assess changes in BMD, and predict fracture risk. The investigators will measure areal BMD of the lumbar spine (L1-4), hip, and wrist, and body composition (total and % fat and lean mass) using a DXA machine. For the TBS analysis, no additional image acquisition is required. TBS will be performed as a re-analysis of the lumbar spine taken as part of the standard DXA procedure with specialized software.
Contraceptive provision:
Women will initiate contraception at the study clinic or a family planning clinic, as they are seeking services. Throughout study follow up, the study will assume responsibility for contraceptive provision, including DMPA injections, and care of all other methods desired by women. The staff at the IDI-Kasangati research clinic have extensive experience with the provision of contraception and contraceptive counseling during previous HIV prevention studies.
PrEP provision and adherence monitoring
Co-formulated emtricitabine FTC/TDF will be provided as PrEP by the study. PrEP counseling and provision will follow WHO guidelines, or Ugandan clinical guidelines when they are available. The investigators will measure adherence using three different methods:
- Pill counts will be conducted by the pharmacist during study visits to determine the percentage of expected pills that were used
- Real time monitoring will be conducted using an electronic monitoring system that captures a date-time stamp each time the pill container is opened
- The primary circulating form of TDF, tenofovir (TFV), will be quantified in blood archives from 1) a random sample of up to 15% of women who initiate PrEP to characterize the adherence in the cohort overall and 2) a targeted group of women who have no BMD change and women who experience a fracture.
Laboratory processing to measure markers of bone turnover, subclinical kidney injury, and hypoestrogenism.
Using state-of-the-art assay techniques on archival samples, the investigators will measure 1) established markers of bone turnover and bone health, 2) markers of subclinical kidney injury, and 3) markers of hypoestrogenism. Archived samples will be batch-analyzed.
- Being tested
- FTC/TDF and DMPA, FTC/TDF, DMPA, Neither DMPA nor FTC/TDF
- Medical subject headings
- Bone Demineralization, Pathologic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FTC/TDF and DMPACombination product
The primary analysis will be separate comparisons of the annualized rates of change in BMD and TBS of the spine and hip between women using PrEP and DMPA concurrently versus women using DMPA only (comparison 1), women using PrEP only (comparison 2), and women using neither (comparison 3). Analyses will account for baseline BMD.
FTC/TDFDrug
The primary analysis will be separate comparisons of the annualized rates of change in BMD and TBS of the spine and hip between women using PrEP and DMPA concurrently versus women using DMPA only (comparison 1), women using PrEP only (comparison 2), and women using neither (comparison 3). Analyses will account for baseline BMD.
DMPADrug
The primary analysis will be separate comparisons of the annualized rates of change in BMD and TBS of the spine and hip between women using PrEP and DMPA concurrently versus women using DMPA only (comparison 1), women using PrEP only (comparison 2), and women using neither (comparison 3). Analyses will account for baseline BMD.
Neither DMPA nor FTC/TDFOther
The primary analysis will be separate comparisons of the annualized rates of change in BMD and TBS of the spine and hip between women using PrEP and DMPA concurrently versus women using DMPA only (comparison 1), women using PrEP only (comparison 2), and women using neither (comparison 3). Analyses will account for baseline BMD.
| Study group | Role | What they receive |
|---|---|---|
| DMPA and PrEP | Active comparator | Not described Receives: Combination Product: FTC/TDF and DMPA |
| DMPA and no PrEP | Active comparator | Not described Receives: Drug: DMPA |
| Condoms only and PrEP | Active comparator | Not described Receives: Drug: FTC/TDF |
| Condoms only and no PrEP | Active comparator | Not described Receives: Other: Neither DMPA nor FTC/TDF |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 months
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.
Measured: 24 months
Secondary outcomes (4)
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.
Measured: Change from Baseline at 24 months
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)
Measured: Change from Baseline at 24 months
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).
Measured: Change from Baseline at 24 months
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.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2018
- Study start15 May 2018
- Primary completion21 Dec 2023
- Study completion21 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Bone DemineralizationStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 500 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Makerere University, MU-JHU CARE, Columbia University, Icahn School of Medicine at Mount Sinai
- Responsible party
- Principal investigator, Renee Heffron, University of Washington
- Investigators
- Renee Heffron, PhD, MPH, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03464266
- Sponsor's protocol ID
- STUDY00001451
- Other IDs
- R01HD089843
- Status last verified
- Jun 2024
- First submitted
- 25 Feb 2018
- Last updated
- 17 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wu L, Ssebuliba T, Muwonge TR, Bambia F, Stein G, Nampewo O, Sapiri O, Goetz BJ, Penrose KJ, Parikh UM, Mujugira A, Heffron R. Alignment of PrEP Use With Potential HIV Exposure in Young Women and Men in Uganda. J Acquir Immune Defic Syndr. 2025 Apr 1;98(4):326-333. doi: 10.1097/QAI.0000000000003573. Epub 2025 Feb 19.
PubMed 39630076Zia Y, Nambala L, Stalter RM, Muwonge TR, Ssebuliba T, Nakyanzi A, Nampewo O, Boyer J, Morrison S, Nsubuga R, Bagaya M, Nyanzi R, Matovu F, Yin M, Wyatt C, Mujugira A, Heffron R for the Kampala Women's Bone Study. Depression and PrEP uptake, interruption, and adherence among young women in Uganda. AIDS Care. 2023 Sep;35(9):1365-1374. doi: 10.1080/09540121.2023.2177250. Epub 2023 Mar 9.
PubMed 36892945
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Concurrent Initiation of DMPA Contraception and Tenofovir PrEP on Bone Loss in Young Women
- ClinicalTrials.gov ID
- NCT03464266
- Acronym / sponsor ID
- STUDY00001451
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 500 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Makerere University, MU-JHU CARE, Columbia University, Icahn School of Medicine at Mount Sinai
- Study start
- 15 May 2018 (actual)
- Primary completion
- 21 Dec 2023 (actual)
- Study completion
- 21 Dec 2023 (actual)
- First posted
- 14 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The proposed research will investigate the hypothesis that TDF-based PrEP and DMPA initiated concurrently by HIV-uninfected women will enhance each other's effects on bone metabolism. The investigators will conduct an open-label prospective study of approximately 500 HIV-uninfected women at substantial risk for HIV-infection who are newly initiating DMPA or using condoms as their only contraceptive in Kampala, Uganda. The investigators will offer PrEP to all of these women and determine the joint effect of PrEP and DMPA on changes in bone mass (Aim 1), bone turnover, subclinical kidney injury, and hypoestrogenism (Aim 2), and conduct mediation analysis to assess the contribution of each pathway to overall losses in bone mass (Aim 3).
- The investigators will assess whether young women using TDF-based PrEP and DMPA concurrently attain lower peak bone mass over a 24-month period and 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 measure BMD annually at 3 anatomical sites (lumbar spine, total hip, and wrist). Additionally, the investigators will derive the trabecular bone score (TBS), an index of lumbar spine trabecular microarchitecture.
- The investigators will investigate whether young women concurrently using TDF-based PrEP and DMPA experience: 1) higher rates of bone turnover, a direct precursor to bone loss and 2) subclinical kidney injury and hypoestrogenism, markers of two mechanistic pathways between TDF and DMPA use and bone mass
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)
- Markers of kidney function (phosphate, glucose, creatinine, total protein, albumin) and
- 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 increased bone turnover markers and PTH. In addition, women concurrently using TDF-based PrEP and DMPA will have more frequent subclinical kidney injury (relative to women without tenofovir exposure) and reduced serum estrogen (relative to women without DMPA exposure).
- 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.
Over a 24-month period, the investigators will follow women quarterly with HIV rapid testing, PrEP adherence counseling and refills, DMPA injections, and provision of other contraceptives as desired. At enrollment and quarterly visits, the investigators will assess physical activity, sexual behavior, and menstrual cycle characteristics. Annually, the investigators will conduct physical exams and anthropometric readings. Sexually transmitted infections will be routinely assessed syndromically, according to national guidelines. Women will be encouraged to consider their HIV risk and fertility desires at every visit and counseled about contraception and PrEP accordingly. Dual energy x-ray absorptiometry (DXA) scans will be performed at baseline and annually thereafter. Blood and urine samples will be obtained quarterly, aliquoted, and archived at minus 80o Celsius.
DXA and TBS assessments:
DXA scans will be conducted at study enrollment (within 1 week of contraceptive initiation), 12, and 24 months after enrollment. DXA is the clinical standard for measuring BMD. It is painless and non-invasive. Women will be exposed to a relatively low level of radiation which is <1/10 the dose of a standard chest x-ray, and less than a day's exposure to natural radiation. BMD by DXA of the hip and spine is generally considered the most reliable way to classify osteoporosis, assess changes in BMD, and predict fracture risk. The investigators will measure areal BMD of the lumbar spine (L1-4), hip, and wrist, and body composition (total and % fat and lean mass) using a DXA machine. For the TBS analysis, no additional image acquisition is required. TBS will be performed as a re-analysis of the lumbar spine taken as part of the standard DXA procedure with specialized software.
Contraceptive provision:
Women will initiate contraception at the study clinic or a family planning clinic, as they are seeking services. Throughout study follow up, the study will assume responsibility for contraceptive provision, including DMPA injections, and care of all other methods desired by women. The staff at the IDI-Kasangati research clinic have extensive experience with the provision of contraception and contraceptive counseling during previous HIV prevention studies.
PrEP provision and adherence monitoring
Co-formulated emtricitabine FTC/TDF will be provided as PrEP by the study. PrEP counseling and provision will follow WHO guidelines, or Ugandan clinical guidelines when they are available. The investigators will measure adherence using three different methods:
- Pill counts will be conducted by the pharmacist during study visits to determine the percentage of expected pills that were used
- Real time monitoring will be conducted using an electronic monitoring system that captures a date-time stamp each time the pill container is opened
- The primary circulating form of TDF, tenofovir (TFV), will be quantified in blood archives from 1) a random sample of up to 15% of women who initiate PrEP to characterize the adherence in the cohort overall and 2) a targeted group of women who have no BMD change and women who experience a fracture.
Laboratory processing to measure markers of bone turnover, subclinical kidney injury, and hypoestrogenism.
Using state-of-the-art assay techniques on archival samples, the investigators will measure 1) established markers of bone turnover and bone health, 2) markers of subclinical kidney injury, and 3) markers of hypoestrogenism. Archived samples will be batch-analyzed.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| DMPA and PrEP | Active comparator | Combination Product: FTC/TDF and DMPA |
| DMPA and no PrEP | Active comparator | Drug: DMPA |
| Condoms only and PrEP | Active comparator | Drug: FTC/TDF |
| Condoms only and no PrEP | Active comparator | Other: Neither DMPA nor FTC/TDF |
Who may qualify
- Ages
- 16 to 25 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- Age 16-25
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FTC/TDF and DMPAThe primary analysis will be separate comparisons of the annualized rates of change in BMD and TBS of the spine and hip between women using PrEP and DMPA concurrently versus women using DMPA only (comparison 1), women using PrEP only (comparison 2), and women using neither (comparison 3). Analyses will account for baseline BMD. | Combination product | DMPA and PrEP |
| FTC/TDFThe primary analysis will be separate comparisons of the annualized rates of change in BMD and TBS of the spine and hip between women using PrEP and DMPA concurrently versus women using DMPA only (comparison 1), women using PrEP only (comparison 2), and women using neither (comparison 3). Analyses will account for baseline BMD. | Drug | Condoms only and PrEP |
| DMPAThe primary analysis will be separate comparisons of the annualized rates of change in BMD and TBS of the spine and hip between women using PrEP and DMPA concurrently versus women using DMPA only (comparison 1), women using PrEP only (comparison 2), and women using neither (comparison 3). Analyses will account for baseline BMD. | Drug | DMPA and no PrEP |
| Neither DMPA nor FTC/TDFThe primary analysis will be separate comparisons of the annualized rates of change in BMD and TBS of the spine and hip between women using PrEP and DMPA concurrently versus women using DMPA only (comparison 1), women using PrEP only (comparison 2), and women using neither (comparison 3). Analyses will account for baseline BMD. | Other | Condoms only and no PrEP |
Primary outcome
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.
Time frame: 24 months
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.
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.
Time frame: 24 months
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.
4 secondary outcomes
The investigators will investigate whether young women concurrently using TDF-based PrEP and DMPA experience higher rates of bone turnover.
Time frame: Change from Baseline at 24 months
The investigators will investigate whether young women concurrently using TDF-based PrEP and DMPA experience higher rates of subclinical kidney injury.
Time frame: Change from Baseline at 24 months
The investigators will investigate whether young women concurrently using TDF-based PrEP and DMPA experience higher rates of hypoestrogenism.
Time frame: Change from Baseline at 24 months
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
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2024.
- Derived from this study: PubMed 39630076Wu L, Ssebuliba T, Muwonge TR, Bambia F, Stein G, Nampewo O, Sapiri O, Goetz BJ, Penrose KJ, Parikh UM, Mujugira A, Heffron R. Alignment of PrEP Use With Potential HIV Exposure in Young Women and Men in Uganda. J Acquir Immune Defic Syndr. 2025 Apr 1;98(4):326-333. doi: 10.1097/QAI.0000000000003573. Epub 2025 Feb 19.
- Derived from this study: PubMed 36892945Zia Y, Nambala L, Stalter RM, Muwonge TR, Ssebuliba T, Nakyanzi A, Nampewo O, Boyer J, Morrison S, Nsubuga R, Bagaya M, Nyanzi R, Matovu F, Yin M, Wyatt C, Mujugira A, Heffron R for the Kampala Women's Bone Study. Depression and PrEP uptake, interruption, and adherence among young women in Uganda. AIDS Care. 2023 Sep;35(9):1365-1374. doi: 10.1080/09540121.2023.2177250. Epub 2023 Mar 9.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Renee Heffron, PhD, MPH principal investigator
University of Washington
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing FTC/TDF and DMPA, FTC/TDF and DMPA in people with Bone Demineralization and Hypoestrogenism, run by University of Washington at 1 site in Uganda.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03464266, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2024; AzTrials last refreshed its copy on 30 Oct 2026.