Plain English Summary
Background and study aims
Tuberculosis (TB) is a highly contagious bacterial infection. It is generally spread by breathing in tiny droplets released into the air by an infected person coughing or sneezing. TB usually affects the lungs, but it can also affect other areas of the body such as the bones, brain and kidneys. When a person is suffering from active TB, they are visibly unwell and can spread the infection to others. Many people however have latent TB, where the bacteria remain in an inactive state in the body. A person with latent TB has no symptoms and cannot spread the infection to others. Without treatment, the infection can become active at any time, and so monitoring people with latent TB is a vital part of controlling the spread of TB in general. Isoniazid is an antibacterial medication which has been used for many years to treat active TB infections. This drug is also commonly used to prevent active TB developing in people who have come into contact with an infected person. The aim of this study is the way that isoniazid preventative treatment (IPT) affects the body in people with latent TB, and if it can increase immunity to TB in general.
Who can participate?
Healthy people above 5 years of age, who are living with someone diagnosed with active TB.
What does the study involve?
Participants are randomly allocated into two groups. The first group receive isoniazid tablets for six months as well as attending monthly clinic visits. The second group attend monthly clinic visits only. All participants are tested for latent TB infection using a blood test at the start of the study, and then again after six months.
What are the possible benefits and risks of participating?
Participants benefit from receiving a free blood test to screen them for TB and HIV, as well as education about the medication they may be taking so that they are fully prepared for any possible side effects. Risks of participating are minimal, including pain or bruising from blood tests, as well as finding the interviews tiring.
Where is the study run from?
1. Kitebi Health Center III (Uganda)
2. Kisenyi Health Center IV (Uganda)
When is the study starting and how long is it expected to run for?
May 2011 to January 2012
Who is funding the study?
1. Seventh Framework Programme (Belgium)
2. Wellcome Trust (UK)
Who is the main contact?
Dr Irene Andia-Biraro
Trial website
Contact information
Type
Scientific
Primary contact
Dr Irene Andia-Biraro
ORCID ID
http://orcid.org/0000-0002-8303-6046
Contact details
Department of Internal Medicine
School of Medicine
College of Health Sciences
Makerere University
P. O. Box 7072
Kampala
041
Uganda
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
The effect of isoniazid preventive therapy on immune responses of household contacts with latent tuberculosis infection
Acronym
Study hypothesis
Household contacts of active tuberculosis patients with latent tuberculosis infection would present with mixed Th1/Th2 cytokine profiles and treatment of the latently infected people with isoniazid would reverses the immune equilibrium from Th2 responses back to Th1 immune dominance.
Ethics approval
1. The Makerere University College of Health Sciences Ethical Review Board, 10/09/2009, ref: 2009-140
2. Uganda National Council for Science and Technology, 16/09/2009, ref: HS 676
Study design
Redomised controlled trial nested within a cohort study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Latent tuberculosis infection
Intervention
Household contacts that were eligible for the study were randomized to receive either isoniazid preventive therapy (IPT) and monthly visits or monthly visits only. Household contacts in the IPT arm were offered self-administerd isoniazid (5mg/kg to a max of 300mg) plus pyridoxine 25mg daily for six months.
Intervention type
Drug
Phase
Not Applicable
Drug names
Isoniazid
Primary outcome measure
1. Net cytokine responses measured from Quantiferon supernatants using an 11-analyte Bio-Plex human cytokine bead array consisting of IFN-γ, IL-2, TNF-α, IL-4, IL-5, IL-13, IL-10, IL-17a, IL-17f, IL-21, and IL-22, among the household contacts at the end of six-months follow up
2. Mtb specific antibody concentrations to purified protein derivative (PPD), culture filtrate protein 10 (CFP-10), early secreted antigenic target 6 (ESAT-6) antigens using an in-house IgG ELISA assay, among the household contacts at the end of six-months follow up
Secondary outcome measures
1. The spontaneous cytokine responses measured from Quantiferon supernatants using an 11-analyte Bio-Plex human cytokine bead array consisting of IFN-γ, IL-2, TNF-α, IL-4, IL-5, IL-13, IL-10, IL-17a, IL-17f, IL-21, and IL-22 at the end of six-months follow up
2. Any side effects due to IPT found during clinical assessment at each monthly clinic visit or reported as they occur
3. Any changes in TST and QFN test reactions between baseline and at the end of six-months follow up
4. Incidence of active TB acquired during the course of the six-months follow up
Overall trial start date
01/03/2009
Overall trial end date
20/10/2014
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Household contacts exposed to patients with sputum smear positive tuberculosis that are:
1. Above the age of 5 years
2. HIV negative
3. Tested positive on both the tuberculin skin test and the QuantiFERON®-TB Gold In-Tube® test (Cellestis GmbH (Europe), Hannover, Germany; QFN)
Participant type
Other
Age group
Mixed
Gender
Both
Target number of participants
The target number is 145
Participant exclusion criteria
Household contacts excluded if they have:
1. Signs and symptoms of active tuberculosis
2. Liver disease
3. Epilepsy
Recruitment start date
01/05/2011
Recruitment end date
31/01/2012
Locations
Countries of recruitment
Uganda
Trial participating centre
Kitebi Health Center III
Kampala
041
Uganda
Trial participating centre
Kisenyi Health Center IV
Kampala
041
Uganda
Sponsor information
Organisation
College of Health Sciences, Makerere University
Sponsor details
P. O. Box 7072
Kampala
041
Uganda
Sponsor type
University/education
Website
Funders
Funder type
Research organisation
Funder name
Wellcome Trust Strategic Award through the Makerere University-Uganda Virus Research Institute Infection and Immunity Research Training Programme (MUII)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Seventh Framework Programme
Alternative name(s)
EC Seventh Framework Programme, European Commission Seventh Framework Programme, EU Seventh Framework Programme, European Union Seventh Framework Programme, FP7
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
Results and Publications
Publication and dissemination plan
The manuscript of the trial findings are about to be published and the journal required the study to be registered before it could publish the work.
Intention to publish date
31/10/2015
Participant level data
Available on request
Basic results (scientific)
Publication list
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/26493989