UMMPUT (Urine metabolomics of MDR-TB patients undergoing treatment)
Research type
Research Study
Full title
Exploring the potential of drug metabolome signatures to predict compliance and toxicity in multi-drug resistant tuberculosis, using global urine metabolomics approach
IRAS ID
262866
Contact name
Mrinal Kumar Das
Contact email
Sponsor organisation
University of Leicester
Duration of Study in the UK
1 years, 0 months, 0 days
Research summary
Summary of Research
Multidrug resistant tuberculosis (MDR-TB) is a pandemic condition with an annual morbidity of close to half a million and mortality of over 200,000. Critically, treatment failure accounts for close to 50% of total MDR-TB cases reported and is the major cause of mortality in drug resistant TB. The treatment regimen for MDR-TB (20-24 months) is lengthy and consists of drugs of lower efficacy and higher toxicity than frontline drugs used in drug-susceptible cases. Ineffective treatment of MDR-TB cases increases the chance of MDR-TB transmission and the development of extensive (XDR) or total (TDR) drug resistant variants.
The primary panacea to the problem of MDR-TB is new drugs with better efficacy and lower toxicity. However, in the absence of new drugs, technical support during treatment management both in terms of early prediction of treatment outcome and in monitoring compliance (linked to drug-toxicity) will hold the key in this regard. However there is no clinical/biochemical parameter to predict such outcome.
Drugs, post administration undergo metabolism inside the body and form breakdown products, adducts and conjugates and these metabolised products are collectively known as drug metabolites. They are important in pharmacology as some of these metabolised products are the actual active principle against a target, some can explain drug related side effects and long retaining metabolites (in biofluid) can act as adherence marker to monitor compliance. Therefore, we hypothesise that monitoring drug metabolite in urine of MDR-TB patient undergoing treatment should enable us to identify markers that can predict toxicity and/or monitor compliance. However, the metabolite map of drugs used in MDR-TB is ill-defined. In this project we are mapping the metabolised product of MDR-TB drugs using a urine metabolomics approach and from the pool of metabolite we will identify markers for toxicity prediction and treatment adherence.Summary of Results
The study was proposed to with recruitment of 5 multi drug resistance cases. The study was carried out to identify level of drug and drug metabolites in urine of Multi-drug resistant tuberculosis patient taking second line drugs at different time points (2 hrs, 8hrs, 12, hrs, and 24 hrs) of taking the drugs.
However, due to pandemic during the study and lower reports of potential study subjects only 1 patient could be recruited during the study period of 3.2 years. Therefore the result of the study is inconclusive.REC name
Wales REC 6
REC reference
19/WA/0237
Date of REC Opinion
27 Aug 2019
REC opinion
Favourable Opinion