Periodic Reporting for period 2 - SMA-TB (A novel Stratified Medicine Algorithm to predict treatment responses to host-directed therapy in TB patients.)
Reporting period: 2021-07-01 to 2022-12-31
Tuberculosis (TB), is a disease caused by bacteria that attack the lungs and it can persist throughout a person’s life or even kill them. The treatment is very long and its success depends on the particular strain of bacteria in that patient being treatable by the available drugs. Resistant strains (MDR-TB), not killed by the common drugs, are much more difficult to treat, which makes the treatment much longer and costly, more unpleasant for patients and a burden for health systems. Moreover, up to 50 % of TB patients can suffer of permanent lung damage which can impair their quality of life. Host-directed treatments (HDTs) are a new type of treatment that boost the patient’s defences and ability to fight off the disease rather than just killing the bacteria. Using HDT treatments together with the antibiotics might mean a shorter time taking medicine and better results for patients.Our hypothesis is that to include an HDT that reduces inflammation in the medicines the patients are already taking can help to reduce permanent lung damage and even the lenght of treatment.
Taking into account all these, the SMA-TB Project aims to do three things:
1-To run a high-quality clinical trial (RCT) in which patients being treated for TB are also given common anti-inflammatories, aspirin or ibuprofen, which reduce inflammation. It is hoped that this will show that the use of anti-inflammatory means a better health-related quality of life for TB patients and better management of their disease.
2-To identify biomarkers to reliably predict how each patient’s disease will progress, who can be treated successfully by the standard treatment and who can benefit of completing the drug treatment with HDT. To do this the researchers will collect information from a large group of patients and analyse it using computers and mathematical models that are able to pick out patterns from huge amounts of information.
3-To make a mathematical tool (algorithm) that doctors can use to identify which patients will have worse outcomes or can benefit of adding an HDT, and to adjust their treatment accordingly (personalized treatment).
Taking into account all these, the SMA-TB Project aims to do three things:
1-To run a high-quality clinical trial (RCT) in which patients being treated for TB are also given common anti-inflammatories, aspirin or ibuprofen, which reduce inflammation. It is hoped that this will show that the use of anti-inflammatory means a better health-related quality of life for TB patients and better management of their disease.
2-To identify biomarkers to reliably predict how each patient’s disease will progress, who can be treated successfully by the standard treatment and who can benefit of completing the drug treatment with HDT. To do this the researchers will collect information from a large group of patients and analyse it using computers and mathematical models that are able to pick out patterns from huge amounts of information.
3-To make a mathematical tool (algorithm) that doctors can use to identify which patients will have worse outcomes or can benefit of adding an HDT, and to adjust their treatment accordingly (personalized treatment).
We have submitted all the deliverables and successfully achieved all the milestones for the first and second reporting period (M1-M36).
Despite the delay imposed by COVID-19 and the drop in TB notifications worldwide after the pandemic (WHO, Global TB Report 2022), the SMA-TB Clinical Trial (CT) started in the 3/3 sites (2 in South Africa and 1 in Georgia) during the first project period and the milestone of more than 50% patients recruited has been achieved during the second reporting period.
A capacity building toolkit which includes protocols, videos and others was developed within the 1st period and updated during the 2nd.
Consortium partners involved in WP2 have worked with samples from previously established cohorts and first batch of SMA-TB samples. WP3 has identified potential biomarkers through a systems biology approach using mathematical modelling and started setting up the model with WP2 partners’ data. set the bases for the upcoming analysis with SMA-TB generated data and highlighted some of the proteins as potential biomarkers.
All the partners of the consortium have been working on communication and dissemination tasks of the project:
-Prepared short stories videos of the project’s impact.
-Collaborated with the Public Health Agency of Barcelona (ASPB) in the creation of leaflets (translated to 12 languages) to provide easily understandable information on TB to local vulnerable communities. This leaflet was used during a TB screening intervention of Ukrainian war refugees in Barcelona.
-Two newsletters issued and spread through different platforms.
-Engagement with local communities and stakeholders to explain to them the SMA-TB project and organize with them joint public activities.
-Links with other EC funded projects to conduct joint activities: DRTB-HDT (GA Nº 847465) MISTRAL (GA Nº 847943), STATIN-TB (GA Nº RIA2017T-2004); and Innova4TB (GA Nº 823854).
-9 open-access publications, 7 posters/talks.
SMA-TB has been using the EU Open Free Repository Zenodo and created SMA-TB Zenodo community to openly publish templates generated as part of the SMA-TB Capacity-building toolkit, which others can adapt and reuse. Accessible at: https://zenodo.org/communities/sma-tb/?page=1&size=20.
SMA-TB outputs generated up to now that might be exploited by others: e-consent video, toolkit related to the CT, laboratory technical capacity of staff, templates to be used for Project Management and Clinical Trial Monitoring, X-ray score prototype, Exhaled Breath Collection device.
Scientific/Technical management and administrative coordination are still successfully ongoing. The Project Manager Team gives specific support and advice to the partners with the lack or small experience in H2020 projects. The Consortium has conducted 3 annual meetings (1 online, due to the pandemic) and 2 General Assemblies, plus several management and scientific internal meetings. The Consortium and the EC have been working on different measures to cope with the impact of COVID-19 pandemic in the progress of SMA-TB project.
Despite the delay imposed by COVID-19 and the drop in TB notifications worldwide after the pandemic (WHO, Global TB Report 2022), the SMA-TB Clinical Trial (CT) started in the 3/3 sites (2 in South Africa and 1 in Georgia) during the first project period and the milestone of more than 50% patients recruited has been achieved during the second reporting period.
A capacity building toolkit which includes protocols, videos and others was developed within the 1st period and updated during the 2nd.
Consortium partners involved in WP2 have worked with samples from previously established cohorts and first batch of SMA-TB samples. WP3 has identified potential biomarkers through a systems biology approach using mathematical modelling and started setting up the model with WP2 partners’ data. set the bases for the upcoming analysis with SMA-TB generated data and highlighted some of the proteins as potential biomarkers.
All the partners of the consortium have been working on communication and dissemination tasks of the project:
-Prepared short stories videos of the project’s impact.
-Collaborated with the Public Health Agency of Barcelona (ASPB) in the creation of leaflets (translated to 12 languages) to provide easily understandable information on TB to local vulnerable communities. This leaflet was used during a TB screening intervention of Ukrainian war refugees in Barcelona.
-Two newsletters issued and spread through different platforms.
-Engagement with local communities and stakeholders to explain to them the SMA-TB project and organize with them joint public activities.
-Links with other EC funded projects to conduct joint activities: DRTB-HDT (GA Nº 847465) MISTRAL (GA Nº 847943), STATIN-TB (GA Nº RIA2017T-2004); and Innova4TB (GA Nº 823854).
-9 open-access publications, 7 posters/talks.
SMA-TB has been using the EU Open Free Repository Zenodo and created SMA-TB Zenodo community to openly publish templates generated as part of the SMA-TB Capacity-building toolkit, which others can adapt and reuse. Accessible at: https://zenodo.org/communities/sma-tb/?page=1&size=20.
SMA-TB outputs generated up to now that might be exploited by others: e-consent video, toolkit related to the CT, laboratory technical capacity of staff, templates to be used for Project Management and Clinical Trial Monitoring, X-ray score prototype, Exhaled Breath Collection device.
Scientific/Technical management and administrative coordination are still successfully ongoing. The Project Manager Team gives specific support and advice to the partners with the lack or small experience in H2020 projects. The Consortium has conducted 3 annual meetings (1 online, due to the pandemic) and 2 General Assemblies, plus several management and scientific internal meetings. The Consortium and the EC have been working on different measures to cope with the impact of COVID-19 pandemic in the progress of SMA-TB project.
The potential impacts of SMA-TB are:
-By integrating data from different aspects of ill patients, to understand them as a whole, to address their needs in a holistic way and to increase their well-being and quality of life.
-SMA-TB will evaluate 2 enhanced treatment regimens including host-directed therapies in a clinical trial. If proven useful, these enhanced treatment regiments will be more effective and targeted, reduce tissue damage, reduce treatment length and sequelae, and increase the cure rates and pathogen clearance. They have the potential to result in a better clinical practice, care management, and increased well-being of patients.
-The validation of host and pathogen biomarkers previously identified by SMA-TB partners or others, and the identification of new ones.
-The generation of a stratification algorithm that will help to identify patients at risk of negative outcomes, to model treatment response, efficacy or toxicity, and to propose personalized options during TB clinical management.
-To provide knowledge on detection, effective infection control, and surveillance of TB and multidrug resistance.
Besides achieving the scientific objectives set, SMA-TB project will:
- Favour employment by promoting the incorporation of new talent in EU.
- Favour education by contributing to the education of a new generation of scientists and other health care workers, administrative and other personnel, but also other people (general society).
- Engage society and stakeholders and contribute to the advance and sharing of knowledge.
- Identify any potential commercial products, methods, or any other exploitable outputs and outcomes that might arise from this project and exploit them during and or beyond the project if considered feasible.
-By integrating data from different aspects of ill patients, to understand them as a whole, to address their needs in a holistic way and to increase their well-being and quality of life.
-SMA-TB will evaluate 2 enhanced treatment regimens including host-directed therapies in a clinical trial. If proven useful, these enhanced treatment regiments will be more effective and targeted, reduce tissue damage, reduce treatment length and sequelae, and increase the cure rates and pathogen clearance. They have the potential to result in a better clinical practice, care management, and increased well-being of patients.
-The validation of host and pathogen biomarkers previously identified by SMA-TB partners or others, and the identification of new ones.
-The generation of a stratification algorithm that will help to identify patients at risk of negative outcomes, to model treatment response, efficacy or toxicity, and to propose personalized options during TB clinical management.
-To provide knowledge on detection, effective infection control, and surveillance of TB and multidrug resistance.
Besides achieving the scientific objectives set, SMA-TB project will:
- Favour employment by promoting the incorporation of new talent in EU.
- Favour education by contributing to the education of a new generation of scientists and other health care workers, administrative and other personnel, but also other people (general society).
- Engage society and stakeholders and contribute to the advance and sharing of knowledge.
- Identify any potential commercial products, methods, or any other exploitable outputs and outcomes that might arise from this project and exploit them during and or beyond the project if considered feasible.