NCT02062580

Brief Summary

In sub-Saharan Africa (SSA), more than 300,000 babies with HIV die each year. HIV-infected children develop AIDS and die faster in SSA than those in developed countries. Bacille Calmette-Guerin (BCG) vaccine is given to infants at birth in SSA to protect them from severe forms of TB. BCG is known to cause immune cells to be active and replicate faster. The immune system of neonates also responds differently to BCG that to other vaccines and infections. We hypothesize that the routine immunization of neonates with BCG contributes to generalized immune activation in HIV-exposed infants resulting in skewed immune responses to vaccines and infections and increased rates of disease progression in those infants that become HIV-infected. However, delaying BCG until HIV testing is completed would result in operational difficulties, and may not induce the appropriate immune response. Delayed BCG would also render many HIV-exposed uninfected infants at high risk for disseminated TB. We plan to assess immune cells in infants to determine the impact of the timing of BCG vaccination on immune responses to tuberculosis (TB) and other vaccines. We will also compare the immune activation and disease progression of those infants that become HIV-infected in the BCG or control arms. Our results will provide key insights into the effect of BCG vaccination on immune responses to HIV as well as inform the optimal timing of BCG vaccination for HIV-exposed infants.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
149

participants targeted

Target at P75+ for phase_2

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2010

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2012

Completed
1.9 years until next milestone

First Submitted

Initial submission to the registry

February 12, 2014

Completed
1 day until next milestone

First Posted

Study publicly available on registry

February 13, 2014

Completed
3.1 years until next milestone

Results Posted

Study results publicly available

March 15, 2017

Completed
Last Updated

March 15, 2017

Status Verified

January 1, 2017

Enrollment Period

1.8 years

First QC Date

February 12, 2014

Results QC Date

October 25, 2016

Last Update Submit

January 25, 2017

Conditions

HIV ExposureHIV Infection

Keywords

Vaccine immunogenicityImmune activation

Outcome Measures

Primary Outcomes (1)

  • T Cell Activation

    Percentage of all CD4+ T cells expressing HLADR (NOT BCG-specific activation as in Tchakoute et al and as in secondary outcome). The n is smaller than the enrollment number as some participants were lost to follow-up, some were excluded due to HIV infection etc, and some samples did not have sufficient cells to analyse.

    at 6 weeks

Secondary Outcomes (1)

  • Vaccine Immunogenicity

    6 weeks after BCG vaccination

Study Arms (2)

Delayed BCG

ACTIVE COMPARATOR

BCG delayed to 8 weeks of age

Biological: BCG

Early BCG

OTHER

BCG at birth; standard of care

Biological: BCG

Interventions

BCGBIOLOGICAL
Delayed BCGEarly BCG

Eligibility Criteria

AgeUp to 24 Hours
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17)

You may qualify if:

  • Healthy neonate
  • Maternal HIV
  • \> 36 weeks gestation
  • Birth weight \> 2.4kg
  • Remaining in area 4 months

You may not qualify if:

  • Complications during pregnancy and delivery
  • Household TB contacts

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (3)

  • Gasper MA, Hesseling AC, Mohar I, Myer L, Azenkot T, Passmore JS, Hanekom W, Cotton MF, Crispe IN, Sodora DL, Jaspan HB. BCG vaccination induces HIV target cell activation in HIV-exposed infants in a randomized trial. JCI Insight. 2017 Apr 6;2(7):e91963. doi: 10.1172/jci.insight.91963.

    PMID: 28405623DERIVED

  • Blakney AK, Tchakoute CT, Hesseling AC, Kidzeru EB, Jones CE, Passmore JA, Sodora DL, Gray CM, Jaspan HB. Delayed BCG vaccination results in minimal alterations in T cell immunogenicity of acellular pertussis and tetanus immunizations in HIV-exposed infants. Vaccine. 2015 Sep 11;33(38):4782-9. doi: 10.1016/j.vaccine.2015.07.096. Epub 2015 Aug 7.

    PMID: 26259542DERIVED

  • Tchakoute CT, Hesseling AC, Kidzeru EB, Gamieldien H, Passmore JA, Jones CE, Gray CM, Sodora DL, Jaspan HB. Delaying BCG vaccination until 8 weeks of age results in robust BCG-specific T-cell responses in HIV-exposed infants. J Infect Dis. 2015 Feb 1;211(3):338-46. doi: 10.1093/infdis/jiu434. Epub 2014 Aug 8.

    PMID: 25108027DERIVED

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Results Point of Contact

Title
Heather Jaspan
Organization
University of Cape Town and University of Washington
hbjaspan@gmail.com
+2721 4066823

Study Officials

  • Heather B Jaspan, MD, PHD

    University of Cape Town

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Senior Lecturer

Study Record Dates

First Submitted

February 12, 2014

First Posted

February 13, 2014

Study Start

June 1, 2010

Primary Completion

April 1, 2012

Last Updated

March 15, 2017

Results First Posted

March 15, 2017

Record last verified: 2017-01