Study of Effects of Tenofovir on Bone Health and Kidneys During Pregnancy and Breastfeeding

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Gilead Sciences
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01066858
First received: February 9, 2010
Last updated: December 31, 2013
Last verified: December 2013
  Purpose

The purpose of this study is to look at the effects of tenofovir disoproxil fumarate (an anti-HIV medication) on the bone health and kidneys of women with HIV during pregnancy and while breastfeeding. The study will also look at the changes in overall health, bone health and how the kidneys work in the infants of these women.


Condition Intervention Phase
HIV Infections
Drug: Tenofovir disoproxil fumarate (TDF)
Phase 4

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Maternal and Infant Monitoring for Evidence of Toxicity Related to Tenofovir Exposure: The Bone and Kidney Health Substudy of the IMPAACT 1077 PROMISE Protocol (Promoting Maternal and Infant Survival Everywhere)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Antepartum Component: Creatinine clearance (CrCl) [ Time Frame: For women and infants: at delivery/birth, up to Week 1 ] [ Designated as safety issue: No ]
  • Antepartum Component: Bone resorption (Dpyr) [ Time Frame: For women and infants: at delivery/birth, up to Week 1 ] [ Designated as safety issue: No ]
  • Antepartum Component: Lumbar spine bone mineral density (BMD) via dual energy e-ray absorptiometry (DXA) [ Time Frame: For women: at delivery/birth, up to Week 1 ] [ Designated as safety issue: No ]
  • Antepartum Component: Lumbar spine bone mineral content (BMC) and whole body BMC via DXA [ Time Frame: For infants: at delivery/birth, up to Week 1 ] [ Designated as safety issue: No ]
  • Antepartum Component: Length-for-age Z-score [ Time Frame: For infants: at delivery/birth, up to Week 1 and Week 26 ] [ Designated as safety issue: No ]
  • Postpartum Component: CrCl [ Time Frame: For women: at postpartum entry (delivery/birth, up to Week 1) and Week 74; for infants: at Week 26 ] [ Designated as safety issue: No ]
  • Postpartum Component: Dpyr [ Time Frame: For women: at Week 74; for infants: at Week 26 ] [ Designated as safety issue: No ]
  • Postpartum Component: Lumbar spine BMD via DXA [ Time Frame: For women: at postpartum entry (delivery/birth, up to Week 1) and Week 74 ] [ Designated as safety issue: No ]
  • Postpartum Component: Lumbar spine BMC via DXA [ Time Frame: For infants: at Week 26 ] [ Designated as safety issue: No ]
  • Postpartum Component: Length-for-age Z-score [ Time Frame: For infants: at postpartum entry (delivery/birth, up to Week 1) and Week 26 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • CrCl [ Time Frame: For women: Weeks 6, 26, and 74; for infants: at Weeks 10, 26, and 74 ] [ Designated as safety issue: No ]
  • BMD [ Time Frame: For women: at delivery and change in hip BMD from delivery to Week 74 ] [ Designated as safety issue: No ]
  • Dpyr [ Time Frame: For women: at Weeks 6, 26, and 74; for infants: at Weeks 10, 26, and 74 ] [ Designated as safety issue: No ]
  • Mineral composition of breast milk [ Time Frame: For women: at Weeks 1, 6, 26, and 74 ] [ Designated as safety issue: No ]
  • Lumbar spine BMC [ Time Frame: For infants: Week 26 ] [ Designated as safety issue: No ]
  • Infant growth [ Time Frame: For infants: at Weeks 10 and 74 ] [ Designated as safety issue: No ]
  • Concentration of hormonal growth factors (for infants) [ Time Frame: For infants: at birth and Weeks 10, 26, and 74 ] [ Designated as safety issue: No ]

Estimated Enrollment: 875
Study Start Date: March 2011
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Maternal/infant antepartum exposure
  • HIV-infected women exposed to TDF during pregnancy
  • Infants of HIV-infected women exposed to TDF during pregnancy
Drug: Tenofovir disoproxil fumarate (TDF)
Some participants will receive varying doses of TDF during pregnancy or breastfeeding as part of the larger study (IMPAACT 1077 PROMISE).
Maternal/infant postpartum exposure
  • HIV-infected women exposed to TDF while breastfeeding
  • Infants of HIV-infected women exposed to TDF while breastfeeding
Drug: Tenofovir disoproxil fumarate (TDF)
Some participants will receive varying doses of TDF during pregnancy or breastfeeding as part of the larger study (IMPAACT 1077 PROMISE).
Maternal/infant antepartum no exposure
  • HIV-infected women not exposed to TDF during pregnancy
  • Infants of HIV-infected women not exposed to TDF during pregnancy
Maternal/infant postpartum no exposure
  • HIV-infected women not exposed to TDF during breastfeeding
  • Infants of HIV-infected women not exposed to TDF during breastfeeding

Detailed Description:

A small number of adults (who are not pregnant) and children who take anti-HIV medications develop problems with their kidneys and with the strength of their bones. These problems may be more common when tenofovir disoproxil fumarate (TDF) is used. Studies about these bone and kidney effects have not been done in pregnant and breastfeeding women and their infants.

This is a substudy of a larger study (IMPAACT 1077 PROMISE [Promoting Maternal and Infant Survival Everywhere]) to evaluate the safety of anti-HIV medications used in pregnancy and during breastfeeding. Only participants in the larger study randomly assigned to receive maternal tenofovir disoproxil fumarate (TDF) or no maternal TDF during pregnancy or during breastfeeding will be enrolled in this substudy.

This substudy will look at two groups of participants:

  • An antepartum exposure group to look at the effects of TDF during pregnancy
  • A postpartum exposure group to look at the effects of TDF during breastfeeding

All mother-infant pairs in the substudy will be followed for 74 weeks after delivery. During this time, the women and their infants will have medical checkups and tests. The tests will include tests of blood, urine, cord blood, and breast milk. Some of the women and infants will have a special x-ray called a dual energy e-ray absorptiometry (DXA) scan to measure bone strength. The timing of the tests—at enrollment, at delivery, at 6, 10, 26, or 74 weeks—will vary dependent on which part of this substudy women and infants are enrolled in. Those in charge of the substudy will try to schedule medical visits and tests at the same time as tests scheduled for the larger IMPAACT 1077 study.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

For antepartum (AP) exposure part of P1084s: Mother/infant pairs enrolled in the antepartum components of 1077BF or 1077FF (1077BA and 1077FA respectively) at African clinical sites approved as P1084s DXA sites.

For postpartum (PP) exposure part of P1084s: Mothers and their infants enrolled in the postpartum component of 1077BF (107BP) at African clinical sites approved as P1084s DXA sites.

Criteria

Antepartum (AP) Part of Study (TDF Exposure During Pregnancy)

Inclusion Criteria:

  • Mother-infant pair enrolled in 1077BA or 1077FA
  • At a clinical site that has been approved as a P1084s DXA site
  • Enrolled in the substudy up to the Week 2 visit of 1077BA/1077FA (within 21 days after 1077BA/1077FA study entry) and prior to the start of labor
  • Willing and able to provide written informed consent to participate in this substudy

Exclusion Criteria:

  • None

Postpartum (PP) Part of Substudy (TDF Exposure During Breastfeeding) (Note: this applies only to the new enrollment to P1084s, i.e., those who were not enrolled to P1084s while on the AP component)

Inclusion Criteria:

  • Mother and their infant enrolled in 1077BP
  • At a clinical site that has been approved as a P1084s DXA site
  • Enrolled in the substudy within 6 to 14 days of delivery, on the same day as enrollment in 1077BP
  • Willing and able to provide written informed consent to participate in this substudy

Exclusion Criteria:

  • TDF exposure during pregnancy [NOTE: TDF use for up to 12 days beginning at labor allowed]
  • Enrolled in the AP part of P1084s
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01066858

Locations
Malawi
College of Med. JHU CRS
Blantyre, Malawi
University of North Carolina Lilongwe CRS
Lilongwe, Malawi
South Africa
Shandukani Research CRS
Johannesburg, Gauteng, South Africa, 2001
Soweto IMPAACT CRS
Johannesburg, Gauteng, South Africa
Durban Paediatric HIV CRS
Durban, KwaZulu-Natal, South Africa, 4001
CAPRISA Umlazi CRS
Umlazi, KwaZulu-Natal, South Africa, 4066
Stellenbosch Univ. CRS
Cape Town, South Africa, 7505
Uganda
MU-JHU Research Collaboration CRS
Kampala, Mpigi, Uganda
Zimbabwe
St Mary's CRS
Chitungwiza, Zimbabwe
Seke North CRS
Chitungwiza, Zimbabwe
UZ-Parirenyatwa CRS
Harare, Zimbabwe
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Chair: George K. Siberry, MD, MPH NICHD/NIH
Study Chair: Lynda Stranix-Chibanda, MBChB, MMED University of Zimbabwe
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01066858     History of Changes
Other Study ID Numbers: P1084s (PROMISE), 10790, IMPAACT P1084s
Study First Received: February 9, 2010
Last Updated: December 31, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
tenofovir
renal and bone toxicity
pregnancy
breastfeeding
mother to child transmission

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Tenofovir
Tenofovir disoproxil
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on October 01, 2014