The role of isoniazid medication in preventing progression to active tuberculosis disease in persons with latent tuberculosis: The effect on the body’s immune system

ISRCTN	ISRCTN15705625
DOI	https://doi.org/10.1186/ISRCTN15705625
Secondary identifying numbers	N/A

Submission date: 17/09/2015
Registration date: 30/09/2015
Last edited: 26/10/2015

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

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

Contact information

Dr Irene Andia-Biraro
Scientific

Department of Internal Medicine
School of Medicine
College of Health Sciences
Makerere University
P. O. Box 7072
Kampala
041
Uganda

ORCID ID	0000-0002-8303-6046

Study information

Study design	Redomised controlled trial nested within a cohort study
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Scientific title	The effect of isoniazid preventive therapy on immune responses of household contacts with latent tuberculosis infection
Study objectives	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(s)	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
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	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 study start date	01/03/2009
Completion date	20/10/2014

Eligibility

Participant type(s)	Other
Age group	Mixed
Sex	Both
Target number of participants	The target number is 145
Key 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)
Key exclusion criteria	Household contacts excluded if they have: 1. Signs and symptoms of active tuberculosis 2. Liver disease 3. Epilepsy
Date of first enrolment	01/05/2011
Date of final enrolment	31/01/2012

Locations

Countries of recruitment

Uganda

Study participating centres

Kitebi Health Center III

Kampala
041
Uganda

Kisenyi Health Center IV

Kampala
041
Uganda

Sponsor information

College of Health Sciences, Makerere University
University/education

P. O. Box 7072
Kampala
041
Uganda

Website	http://.chs.mak.ac.ug
"ROR"	https://ror.org/03dmz0111

Funders

Funder type

Research organisation

Wellcome Trust Strategic Award through the Makerere University-Uganda Virus Research Institute Infection and Immunity Research Training Programme (MUII)

No information available

Seventh Framework Programme
Government organisation / National government

Alternative name(s): EC Seventh Framework Programme, European Commission Seventh Framework Programme, EU Seventh Framework Programme, European Union Seventh Framework Programme, FP7

Results and Publications

Intention to publish date	31/10/2015
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
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.
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	22/10/2015		Yes	No