TB Sequel: Pathogenesis and Risk Factors of Long-term Sequelae of Pulmonary TB (TBSEQUEL)

January 12, 2021 updated by: The Aurum Institute NPC

TB Sequel: Pathogenesis and Risk Factors of Long-term Sequelae of Pulmonary TB Defining Individual Outcomes and Public Health Impact

This is an observational cohort study. Pulmonary tuberculosis (TB) patients will be enrolled at the time of TB diagnosis and prospectively followed for at least two years after TB-treatment initiation with optional prolonged follow-up. Study visits will be performed in the study clinics or if necessary at the participant's home at pre-defined time points after TB treatment initiation. Clinical assessments, biological sample collections and collection of socio-economic data will be performed according to the pre-defined schedule of events.

Study Overview

Detailed Description

The African continent today is emblematic of TB as a global health emergency with little known about the long-term sequelae. It is likely that TB patients from resource-constrained settings, who usually present with more extensive disease, are left with greater lung impairment.

This project aims to advance the understanding of the clinical, microbiologic, and host immune factors affecting the long-term sequelae of pulmonary tuberculosis; to identify the most important factors that contribute to lung impairment, including the immunological response and genetic predisposition of the host and differences in the biology of the pathogen; to determine occurrence of reversible and irreversible costs and socioeconomic consequences for patients; and to facilitate novel interventions to restore and preserve overall health, well-being and financial protection in patients with TB.

The core of the current project is a prospective cohort of up to 1600 patients across four countries (Mozambique, Tanzania, South Africa and The Gambia), enrolled at the time of TB diagnosis, and followed up for at least 2 years. The overall goal of the cohort is to describe and analyse the basis of the long-term clinical consequences of pulmonary TB, with a particular focus on lung injury. The investigators will enroll patients during two years and follow each patient up for at least two years. The project also includes a number of sub-studies: Host-Immunology, Pathogen and Socio-Economic. General laboratory tests and TB specific tests, X-ray, physical examination and cardio-pulmonary assessment will be performed and the obtained clinical data will be recorded in study questionnaires. The investigators will collect and analyse biological specimens (blood, urine and sputum) longitudinally during the period of observation and after all specimens have been stored. In-depth analysis of the host immune response, focusing on potential mechanisms of lung damage, including oxidative injury, proteolytic matrix degradation, and neutrophil-mediated damage, neutrophil-macrophage ratios and markers; and molecular analysis of mycobacterial dynamics and markers in relation to pulmonary and microbiological treatment outcomes, including success, failure, relapse, reinfection and death will be carried out. Socio-economic data, including patient costs, will be collected at the time of TB diagnosis, during treatment, at the end of treatment and during the follow-up period, and analysed to determine how the risk of TB sequelae is linked with the socioeconomic position of the patient, to establish the occurrence of catastrophic costs due to TB and the proportion of patients that resort to potentially irreversible socioeconomic coping strategies.

Accurate data source will be maintained and confidentiality will be guaranteed. Data will be analysed according to the statistical plan. Results of the study will be disseminated to all relevant stakeholders through meetings, reports and publications.

Study Type

Observational

Enrollment (Actual)

1500

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Fajara, Gambia
        • The MRC-Unit
      • Maputo, Mozambique
        • Instituto Nacional de Saúde
    • Gauteng
      • Johannesburg, Gauteng, South Africa, 2092
        • The Clinical HIV Research Unit
      • Mbeya, Tanzania
        • NIMR-Mbeya Medical Research Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

This will be a multi-country, multi-centre observational cohort study, conducted at four recruiting sites in four African countries: 1) University of the Witwatersrand (WITS), Johannesburg in South Africa; 2) NIMR-Mbeya Medical Research Center (NIMR-MMRC), Mbeya in Tanzania; 3) Instituto Nacional de Saúde (INS), Ministry of Health, Mozambique; 4) Medical Research Council (MRC) Unit The Gambia, Fajara, The Gambia.

Description

Inclusion Criteria:

  • At least one sputum sample tested positive for Mtb by Xpert MTB/RIF assay in the study clinic/study laboratory or at least one sputum sample tested positive by culture methods in study laboratory or other TB laboratory
  • Be ≥ 18 years of age
  • Willingness to provide a written consent or witnessed oral consent in the case of illiteracy for participation in the study, prior to patient's first sample or other study-specific data being collected
  • Willing to be tested for HIV infection
  • Agrees to the collection and storage of blood, urine, and sputum specimens for use in future research
  • Willing to start anti-TB treatment after TB diagnosis
  • Living within the study area and willing to inform the study team of any change of address during the treatment and follow-up period

Exclusion Criteria:

  • Has received TB treatment in the last 6 months
  • Has incapacity to produce and provide two sputum samples of sufficient quality (3 ml)
  • Has severe medical or psychiatric condition which in the opinion of the site investigator or designee, might interfere with the ability to give true informed consent and to adhere to the study requirements
  • Is currently imprisoned
  • Taking part in investigational product trials related to TB and/or lung diseases

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Severe pulmonary function impairment
Time Frame: 2 years
Measured by spirometry
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in impairment of pulmonary function
Time Frame: 2 years
Measured by six minute walking test
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 22, 2017

Primary Completion (Anticipated)

June 30, 2022

Study Completion (Anticipated)

June 30, 2022

Study Registration Dates

First Submitted

July 31, 2017

First Submitted That Met QC Criteria

August 15, 2017

First Posted (Actual)

August 16, 2017

Study Record Updates

Last Update Posted (Actual)

January 13, 2021

Last Update Submitted That Met QC Criteria

January 12, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

To be shared amongst the Collaborators, on shared database when the study starts

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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