Research lines of the Experimental Tuberculosis Unit (UTE)
Research line 1: Study of biomarkers of TB disease course and prognosis
Nowadays in TB, there is no validated correlator of protection, disease course or prognosis biomarker, in spite of many resources of the scientific community devoted to find it. Through this research line we aim to identify and validate biomarkers able to monitor response to treatment response and to predict TB disease course and outcomes, and to develop and evaluate tools and strategies to improve the clinical management of patients and their quality of life.
Current projects within this research line:
- SMA-TB Project (A novel Stratified Medicine Algorithm to predict treatment responses to host-directed therapy in TB patients) is an H2020 EU-funded coordinated project (Grant Agreement 847762, http://www.smatb.eu) The objective is to identify and clinically validate host and pathogen biomarkers to predict TB course and outcomes and response to treatment; and to generate a medical algorithm to stratify patients using network-based mathematical modeling for predicting the course of the disease and its response to the intervention, to be applied during clinical management to improve and personalize TB. The PI Dr. Cris Vilaplana (UTE-IGTP) is the project coordinator in which many other institutions from several countries are involved: CNRS-IPBS (France), LUMC (Netherlands), OUS (Norway), LIONEX (Germany), ANAXOMICS (Spain), and TES2A (Spain). PI: Dr. Cris Vilaplana
- “Study of TB Lesions Obtained in Therapeutical Surgery, registered at Clinicaltrials.gov under identifier NCT02715271. Thanks to a long-term collaboration with the National Center of Tuberculosis and Lung Diseases of Tbilisi, Georgia, we study the human tuberculosis lesions obtained during therapeutical surgery. The correlation of the morphologic, microbiological, genetic and histopathological characteristics of TB lesions obtained in therapeutical surgery with the clinical forms and features of the patients will provide essential information: 1) on the role of the host in the mechanisms associated to the generation and evolution of active TB; and 2) about future diagnostic and/or prognostic biomarkers of TB disease. All this information could be used for patients stratification and/or to design new therapeutic strategies. PI: Dr. Cris Vilaplana
- “Design of an integrative algorithm for staging tuberculosis patients to improve patient management at the care level (STAGE-TB)”, multicentric project registered at Clinicaltrials.gov under identifier NCT03691883. TB is a chronic infectious disease that affects 10 million people each year, 1,200 in our country (300 each year in the city of Barcelona). With serious public health consequences, it is associated with other diseases, and is generated and influenced by many social and psychological conditions. Despite this scenario, it has never been staged, and we treat all patients the same way, adjusting treatment only based on microbiology and weight; regardless of the clinic, imaging techniques, epidemiology, psycho-social characteristics of the patients. With the integrated study of the clinical, radiological, analytical, microbiological, epidemiological, psychosocial characteristics and presence of biomarkers, we will be able to stage the tuberculosis disease. PI: Dr. Cris Vilaplana.
- “Development of a CXR score to evaluate the clinical improvement of TB patients (BCN-SA X-ray Score”. In collaboration with the Radiodiagnosis Dept. of the Hospital Universitari Germans Trias i Pujol, the Perinatal HIV Research Unit of Johannesburg, South Africa and the NIAID of the USA. PI: Dr. Cris Vilaplana
- “Evaluation of the trained immunity in monocytes from healthy blood donors (TIMYC)” In this study, the experimental conditions that allow evaluating the trained immune responses of peripheral blood monocytes are established. To accomplish this, monocytes are isolated from a group of healthy volunteers and their responses to various stimuli are studied in vitro. PI: Dr. Pere-Joan Cardona.
Research line 2: Evaluation of new prophylactic and therapeutic strategies against TB
2.1 In experimental models of infection
Mainly through experimental animal models (but also in vitro and in silico models), the UTE has more than 15 years of evaluating new prophylactic and therapeutic strategies against TB. Because of this experience, the UTE has become an international reference to evaluate new drug and vaccine candidates and has been included in several international consortia (funded by the EC and the Bill & Melinda Gates Foundation), and contracted by several research institutes and biotech & pharma companies. Depending on the final aim of the contractor, the unit has a wide portfolio of experimental animal models and services. Within this research line we have the following projects ongoing:
- “Study of the innate mechanisms determining the tolerant response against tuberculosis in the Drosophila melanogaster model (FIS-FLY)”.
2.2 In clinical studies and trials
Novel approaches to improve TB treatment outcomes (to reduce morbidity, mortality, and the duration of TB treatment) and to treat extensively drug-resistant TB (XDR-TB) cases are urgently required. The appropriateness and potential effect of new approaches (as Host-Directed therapies) need to be evaluated in humans.
In this sense, we have o are evaluating the following prophylactical or therapeutical approaches:
- Non-Steroid AntiInflammatory Drugs NSAIDS:
- The NSAIDS-XDR-TB CT (“”Potential Efficacy and Safety of Using Adjunctive Ibuprofen for XDR-TB Tuberculosis”, registered at Clinicaltrials.gov under the Identifier NCT02781909) is a pilot study to estimate the potential efficacy and safety of using adjunctive ibuprofen for the treatment of pre and Extremely Drug Resistant (XDR) tuberculosis. PI: Cris Vilaplana.
- SMA-TB Clinical trial (“Adjunctive Acetylsalicylic Acid and Ibuprofen for Tuberculosis”, registered at Clinicaltrials.gov under code NCT04575519. This CT is being conducted within the H2020 EC-funded SMA-TB Project (smatb.eu). In this CT, 2 repurposed drugs (acetylsalicylic acid and ibuprofen) are evaluated as Host Directed Therapies, administered as an adjunct to standard therapy for drug-sensitive and multi-drug resistant TB in a clinical trial in South Africa (PHRU-WHC) and Georgia (NCTLD). PI: Cris Vilaplana
- Other host-directed therapies:
- “Efficacy of Nyaditum Resae® Against Active TB in Georgia”, registered at Clinicaltrials.gov under the Identifier PI: Pere-Joan Cardona. The aim of this placebo-controlled RCT I to evaluate the efficacy of a supplement food “Nyaditum resae®” in stopping the progression towards active TB by inducing tolerance. PI: Pere-Joan Cardona.
- “Clinical Trial to Evaluate the Efficacy of Food Supplement Manremyc® Against SARS- COV-2 Infection (COVID-19) in Healthcare Workers”, registered at Clinicaltrials.gov under the Identifier NCT04452773. PI: Pere-Joan Cardona.
- “Double-blind, randomized, placebo-controlled clinical trial to evaluate the efficacy of Manremyc® food supplement to prevent the SARS- COV-2 infection (MANRECOVID19)”. A double-blind, randomized, multicenter, placebo-controlled clinical trial is conducted. The purpose of this study is to assess the efficacy of Manremyc® food supplement to prevent the incidence of SARS-CoV-2 infection in a high-risk population, as healthcare workers from Primary Care and hospitals (NCT04452773). Cumulative incidence of COVID-19, levels and types of SARS-CoV-2 antibodies, sick leave incidence, respiratory symptoms, complications of the disease are assessed over a 4-month time frame. At the same time, trained immune response caused by the administration of the Manremyc® is assessed by the determination of immunological populations of PBMC, the response of monocytes to inflammatory cytokines, and the epigenetic study of monocytes to evaluate promoter sites of inflammatory genes. PI: Dr. Pere-Joan Cardona
- Vaccine candidates:
- “Clinical Trial to Evaluate the Efficacy of RUTI® Against SARS-COV-2 Infection (COVID-19) in Healthcare Workers”, registered at Clinicaltrials.gov under the Identifier
- “BRACE – BCG vaccination to Reduce the impact of COVID-19 in healthcare workers following Coronavirus Exposure (BRACE) Trial”, registered at Clinicaltrials.gov under the Identifier Phase III, two group, multicentre, randomised placebo-controlled trial in up to 7244 healthcare workers to determine if BCG vaccine reduces incidence and the severity of COVID-19 disease during the 2020 SARS-CoV-2 pandemic. The trial includes a pre-planned meta-analysis with data from the 2834 participants recruited in first phase of this study which followed the same protocol, but where participants were randomised between BCG and no BCG at the time of receiving a flu vaccination, with a total sample size of 10,078. Randomisation and immunisation will occur at each participating site. Participants will be followed-up for 12 months. PI: Pere-Joan Cardona.
- “Double-blind, randomized, placebo-controlled clinical trial to evaluate the efficacy of RUTI® vaccine to prevent COVID-19 (RUTICOVID19)”, registered registered at Clinicaltrials.gov under identifier NCT04903184. This is a double-blind, randomized, placebo-controlled, 2-arm, parallel, multicenter, phase III, clinical trial to evaluate the efficacy of the RUTI® vaccine to prevent COVID-19 is conducted. Also, the effect on the trained immune response caused by the administration of the RUTI® vaccine is evaluated (NCT04453488; EudraCT:2020-001941-38). This study is carried out in 315 healthcare workers from two Catalan hospitals witch receive 2 treatment doses to be administered on the baseline visit day and after 2 weeks +/- 3 days. Participants are randomized 2: 1 (210 treated with RUTI® vaccine and 105 treated with placebo), and they are followed up for 4 months after the start of treatment. A blood sample is taken at each face-to-face visit to evaluate the serological antibodies of SARS-CoV-2, and medical records are collected during face-to-face visits and telephone interviews. PI: Dr. Pere-Joan Cardona.
Research line 3: Study of Health dimensions and quality of life in the context of infectious diseases
With the belief that there are several dimensions of health (physical, social, emotional, environmental, etc.) and changes in one affects the others, we aim not only to study TB as a disease, but also to understand the TB patient as a whole. Within this research line we have the following projects ongoing:
- Study of health dimensions in tuberculosis: since 2018, the UTE studies the dimensions of health and the impact of tuberculosis on health quality of life of tuberculosis patients in the context of the SH-TBL, STAGE-TB and XDR-NSAIDS-TB cohorts. PI: Dr. Cris Vilaplana
- “Assessment of the Psycho-social Impact of COVID-19 Outbreak (COM-COVID Project)”, registered at ClinicalTrials.gov database under the Identifier: NCT04378452. PI: Dr. Cris Vilaplana.
Staff, students and permanent collaborators:
Head if the Unit:
- Cris Vilaplana, MD, PhD, Microbiologist, Miguel Servet I researcher. orcid.org/0000-0002-2808-7270; https://www.linkedin.com/in/cristina-vilaplana-b444/; cvilaplana(at)gmail.com and cvilaplana(at)igtp.cat
HEAD OF THE UNIT
Dr. Vilaplana (Barcelona, 1975) is a physician, specialist in microbiology and parasitology, working as a PI within the Experimental Tuberculosis Unit at the Germans Trias i Pujol Foundation (IGTP). Her main lines of research are focused on the evaluation of therapeutic strategies to modulate the inflammation in tuberculosis (TB), and in the search of biomarkers and other tools to improve TB patients disease course and management. Author of 61 scientific articles; she has has participated in 22 competitive R&D projects and has more than 15 years-experience in design and evaluation of new therapeutic strategies against TB, both in experimental animal models and in clinical studies. She is a member of the Microbiology and Genetics Dept. of the Universitat Autònoma de Barcelona (UAB), the co-inventor of 4 patents and the founding partner of a spin-off (www.manremyc.cat). Dr. Vilaplana is member of the collaborative networks CIBER Enfermedades Respiratorias, the Collaboration for TB Vaccine Discovery (CTVD) ad the Africa-Europe Host-Directed Therapies Network (HDT-Net). Dr. Vilaplana is coordinating one international clinical study (SH-TBL) involving partners of 5 different countries, one clinical trial in Tbilisi, Georgia (NSAIDS-XDR-TB) and a multi-centric cohort study in Barcelona area (STAGE-TB). She has recently obtained a H2020 project (involving 9 partners from 7 countries) as PI and consortium coordinator. She is a board member of the foundation FUITB (http://www.uitb.cat/fuitb/) and ACTMON foundation (http://www.actmon.org/index.php). Currently enrolled in the Executive Master in Healthcare Organisation Management of ESADE University (candidate 2019). In February 2020 the H2020 SMA-TB project (https://www.smatb.eu/) began, led and coordinated by Dr. Vilaplana, in which a team of 67 people participate, from 9 institutions in 7 different countries, and that includes an international, phase 2, double-blind, randomized, placebo-controlled clinical trial to improve the treatment of tuberculosis with the use of anti-inflammatory drugs. It will last 3 and a half years and will involve 354 patients from South Africa and Georgia. As an extraordinary milestone, it is worth mentioning that in the midst of the COVID-19 pandemic and just one year later, in February 2021, the first patient was included in the clinical trial.
P-J Cardona, MD, PhD, Microbiologist. Head of Microbiology Service, HUGTP https://orcid.org/0000-0001-5623-7873; https://www.linkedin.com/in/perejoancardona/?originalSubdomain=es pjcardona(at)igtp.cat; pj.cardona(at)gmail.com; pcardonai.germanstrias(at)gencat.cat
Technician and administrative team:
- Lilibeth Arias, https://orcid.org/0000-0002-2469-8832 lilibethariascruz(at)gmail.com (Project manager)
- Laura Villegas, secretary.ute(at)gmail.com (Administrative)
- Kaori Levy Da Fonseca, https://orcid.org/0000-0002-7048-9740 klevy(at)igtp.cat (Post-doc researcher)
- Marte Singsås Dragset, marte.dragset(at)ntnu.no; in collaboration with the Norwegian University of Science and Technology, thanks to a Norwegian Research Council Grant. (Post-doc researcher)
- Marta Arch, https://orcid.org/0000-0002-2120-1667 marchl(at)igtp.cat (Pre-doctoral researcher)
- Maria Vidal, mvidal(at)igtp.cat (Pre-doctoral researcher)
- Esther Fuentes, responsible of the Drosophila facility. Efuentes(at)igtp.cat (Technician)
- Gustavo Tapia, MD, Pathologist. Pathology Dept, HUGTIP. gustavotapiam(at)hotmail.com
- Jordi Bechini, MD, PhD, chief of the Radiology Dept, HUGTIP. jbechini.germanstrias(at)gencat.cat
- Ricard Pérez, MD, Radiologist. Radiology Dept, HUGTIP. rperez.germanstrias(at)gencat.cat
- Montse Tenesa, MD, Radiologist. Radiology Dept, HUGTIP. mtenesa.germanstrias(at)gencat.cat
PhD Students and others:
We do continuously accept degree, master and other students from very different fields (medical, biomedic, physics, bioengineering), and we often have open PhD positions. Please do not hesitate in checking our blogsite from time to time and feel free to send an email with a single pdf including your CV and a letter of interest to the following address: secretary.ute(at)gmail.com.
This blog is mantained, managed and its content written by Ms. Laura Villegas.