Clinical Trial: Vitamin A Supplementation for Modulation of Mycobacterium Tuberculosis Immune Responses in Latent Tuberculosis
Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional
Official Title: A Double Blind, Placebo Controlled Randomized Trial of Vitamin A Supplementation for Modulation of Mycobacterium Tuberculosis Immune Responses in Children Aged 5-14 Years With La
Brief Summary:
In populations with high prevalence of latent tuberculosis infection (LTBI), malnutrition (PEM) may influence incident rates of TB. PEM and specific micronutrient deficiencies compromise cell mediated immunity (CMI) and increase susceptibility to, or severity of infections. Vitamin A supplementation significantly reduces all-cause child mortality. The mechanism of the benefits of supplementation on clinical outcomes is largely unknown, but is likely to be related to an influence on the immune system. Vitamin A supplementation promotes lymphogenesis and induces a higher proportion of CD4 naïve T-cells in children. Most cases of LTBI that progress to active disease are vitamin A deficient. Vitamin A deficiency is common in most TB endemic countries. At the MRC, 32% of TBCC contacts were vitamin A deficient.
Hypothesis:
The investigators plan to test the hypotheses: that supplementation with vitamin A will affect the magnitude and quality of immune responses to mycobacterial antigens and progression to clinical disease.
Detailed Summary:
Tuberculosis (TB) remains a significant global health problem. Approximately a third of the world's populations are infected with Mycobacterium tuberculosis and 95% of cases occur in developing countries. This enormous pool of latently infected individuals is expected to pose a major obstacle for TB control in highly endemic countries and globally. In high income, low TB burden countries, targeted testing of TB case contacts and treatment for latent TB infection (LTBI) is practised as a component of TB control strategies. However, this is not practised in high burden, low-income countries. New evidence from mathematical modelling suggests that, to meet millennium development goals, interventions against M. tuberculosis infection will be required.
Children are at increased risk of rapid progression to active disease (usually within a year for infants). , Malnutrition has been identified as a major risk factor for progression to TB because of its profound effect on cellular immune function- the key host defence against TB. There are 2 types of risk associated with malnutrition: acquisition of infection and risk of infection progressing to disease. Therefore, in populations with high prevalence of latent TB infection, co-prevalent malnutrition may influence TB incidence rates.
Vitamin A supplementation has been clearly shown to reduce all-cause child mortality in developing countries. Vitamin A given at recommended doses has a profound effect on improving outcomes in measles and overall childhood mortality and morbidity. The mechanism for this has been attributed to its modulation of immune responses in addition to correcting underlying deficiency.
In TB patients, it is nearly impossible to determine nutritional status before disease and thus determine whether malnutrition led
Sponsor: Medical Research Council Unit, The Gambia
Current Primary Outcome: Measurement of cytokine (IFN-gamma, IL-10, TNF-alpha, TGF-beta) levels produced in response to M. tb. [ Time Frame: 2 years ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- FoxP3 gene expression with RT-PCR on mRNA from PBMCs. [ Time Frame: 2 years ]
- Incidence of probable/confirmed TB; change in weight (mean weight gain) [ Time Frame: 2 years ]
- Qualitative (positive/negative) and quantitative (mean change in counts) reversion of the T-cell assay [ Time Frame: 2 years ]
Original Secondary Outcome: Same as current
Information By: Medical Research Council Unit, The Gambia
Dates:
Date Received: November 14, 2007
Date Started: July 2009
Date Completion: December 2012
Last Updated: April 8, 2015
Last Verified: April 2015
