The Kampala Women's Bone Study

NCT03464266 | Completed Phase 4 DMC

• 2 other identifiers: STUDY00001451R01HD089843
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Bone Demineralization; Hypoestrogenism; Subclinical Kidney Injury; Bone Microarchitecture

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (4)

• The investigators will investigate whether young women concurrently using TDF-based PrEP and DMPA experience higher rates of bone turnover.

  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.

  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.

  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

  24 months

Study Arms (4)

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

Interventions

FTC/TDF and DMPA COMBINATION_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.

DMPA and PrEP

FTC/TDF DRUG

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.

Condoms only and PrEP

DMPA DRUG

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.

DMPA and no PrEP

Neither DMPA nor FTC/TDF OTHER

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.

Condoms only and no PrEP

Eligibility Criteria

• Age: 16 Years - 25 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Washington: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• Makerere University: collaborator
• MU-JHU CARE: collaborator
• Columbia University: collaborator
• Icahn School of Medicine at Mount Sinai: collaborator

Study Sites (1)

Infectious Disease Institute

Kampala, Uganda

Location

Related Publications (2)

• 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.

  PMID: 39630076 DERIVED

• Zia 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.

  PMID: 36892945 DERIVED

MeSH Terms

Conditions

Bone Demineralization, Pathologic

Interventions

N,N-dimethyl-4-anisidine

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Renee Heffron, PhD, MPH

  University of Washington

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Global Health and Epidemiology

Study Record Dates

• First Submitted: February 25, 2018
• First Posted: March 14, 2018
• Study Start: May 15, 2018
• Primary Completion: December 21, 2023
• Study Completion: December 21, 2023
• Last Updated: June 17, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

UG (1)