Condition category
Infections and Infestations
Date applied
17/09/2015
Date assigned
30/09/2015
Last edited
26/10/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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 measures

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

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

http://.chs.mak.ac.ug

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

Federal/National Government

Location

Belgium

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

Results - basic reporting

Publication summary

2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/26493989

Publication citations

Additional files

Editorial Notes