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The Kampala Women's Bone Study

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ClinicalTrials.gov Identifier: NCT03464266
Recruitment Status : Recruiting
First Posted : March 14, 2018
Last Update Posted : December 19, 2018
Sponsor:
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
Information provided by (Responsible Party):
Renee Heffron, University of Washington

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.

Condition or disease Intervention/treatment Phase
Bone Demineralization Hypoestrogenism Subclinical Kidney Injury Bone Microarchitecture Combination Product: FTC/TDF and DMPA Drug: FTC/TDF Drug: DMPA Other: Neither DMPA nor FTC/TDF Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Impact of Concurrent Initiation of DMPA Contraception and Tenofovir PrEP on Bone Loss in Young Women
Actual Study Start Date : May 15, 2018
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : August 2021

Arm Intervention/treatment
Active Comparator: DMPA and PrEP Combination Product: FTC/TDF and DMPA
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.

Active Comparator: DMPA and no PrEP Drug: DMPA
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.

Active Comparator: Condoms only and PrEP Drug: FTC/TDF
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.

Active Comparator: Condoms only and no PrEP Other: Neither DMPA nor FTC/TDF
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.




Primary Outcome Measures :
  1. 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.


  2. 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.



Secondary Outcome Measures :
  1. 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 ]

    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.


  2. 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 ]

    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)


  3. 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 ]

    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).


  4. 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 ]

    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.




Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years to 25 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03464266


Contacts
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Contact: Renee Heffron, PhD, MPH 206-520-3817 rheffron@uw.edu
Contact: Andrew Mujugira, MBChB, PhD mujugira@uw.edu

Locations
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Uganda
Infectious Disease Institute Recruiting
Kampala, Uganda
Contact: Andrew Mujugira, MBChB       Andrew Mujugira <mujugira@uw.edu>   
Contact: Elly Katabira, MBChB       ekatabira@chs.mak.ac.ug   
Sponsors and Collaborators
University of Washington
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
Investigators
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Principal Investigator: Renee Heffron, PhD, MPH University of Washington
  Study Documents (Full-Text)

Documents provided by Renee Heffron, University of Washington:
Study Protocol  [PDF] July 31, 2018


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Responsible Party: Renee Heffron, Assistant Professor, Global Health and Epidemiology, University of Washington
ClinicalTrials.gov Identifier: NCT03464266     History of Changes
Other Study ID Numbers: STUDY00001451
R01HD089843 ( U.S. NIH Grant/Contract )
First Posted: March 14, 2018    Key Record Dates
Last Update Posted: December 19, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Bone Demineralization, Pathologic
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Metabolic Diseases