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

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ClinicalTrials.gov Identifier: NCT03251196
Recruitment Status : Recruiting
First Posted : August 16, 2017
Last Update Posted : February 6, 2018
Sponsor:
Collaborators:
Ludwig-Maximilians - University of Munich
Research Center Borstel
University of Witwatersrand, South Africa
Mbeya Medical Research Centre NIMR
Ministry of Health Instituto Nacional de Saude
Medical Research Council Unit, The Gambia
Karolinska Institutet
Information provided by (Responsible Party):
Tonderai Mabuto, The Aurum Institute NPC

Brief Summary:
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.

Condition or disease Intervention/treatment
Respiratory Tract Infections Tuberculosis, Pulmonary Other: No Intervention, and Observational Study

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.


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Study Type : Observational [Patient Registry]
Estimated Enrollment : 1600 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 2 Years
Official Title: TB Sequel: Pathogenesis and Risk Factors of Long-term Sequelae of Pulmonary TB Defining Individual Outcomes and Public Health Impact
Actual Study Start Date : September 22, 2017
Estimated Primary Completion Date : June 30, 2022
Estimated Study Completion Date : June 30, 2022

Resource links provided by the National Library of Medicine



Intervention Details:
  • Other: No Intervention, and Observational Study
    Observational Study
    Other Name: Observational Study


Primary Outcome Measures :
  1. Severe pulmonary function impairment [ Time Frame: 2 years ]
    Measured by spirometry


Secondary Outcome Measures :
  1. Changes in impairment of pulmonary function [ Time Frame: 2 years ]
    Measured by six minute walking test


Biospecimen Retention:   Samples With DNA
Collection Bloods, Urine and Sputum will be obtained from each patient at different time-points for analysis and storage. They will include, but are not limited to: native urine, native sputum, extracted DNA from positive liquid culture, sputum pellet and surpernatant and whole blood (PAXgene, plasma, serum, PBMC).


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03251196


Contacts
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Contact: Kavi Velen +27 10 590 1391 ext 1391 kvelen@auruminstitute.org
Contact: René A Wills +27 10 590 1399 ext 1399 rwills@auruminstitute.org

Locations
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Gambia
The MRC-Unit Recruiting
Fajara, Gambia
Contact: Beate Kampmann    +220 4495442    bkampmann@mrc.gm   
Mozambique
Instituto Nacional de Saúde Recruiting
Maputo, Mozambique
Contact: Nilesh Bhatt       nbhatt.mz@gmail.com   
South Africa
The Clinical HIV Research Unit Recruiting
Johannesburg, Gauteng, South Africa, 2092
Contact: Mohammed Rassool, Medical    +2711 276 8800    mrassool@witshealth.co.za   
Tanzania
NIMR-Mbeya Medical Research Centre Recruiting
Mbeya, Tanzania
Contact: Nyanda Ntinginya, MD, Phd    +255 25 2503364    nelias@nimr-mmrc.org   
Sponsors and Collaborators
The Aurum Institute NPC
Ludwig-Maximilians - University of Munich
Research Center Borstel
University of Witwatersrand, South Africa
Mbeya Medical Research Centre NIMR
Ministry of Health Instituto Nacional de Saude
Medical Research Council Unit, The Gambia
Karolinska Institutet
Investigators
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Principal Investigator: Gavin J Churchyard Chief Executive Officers

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Tonderai Mabuto, Principal, The Aurum Institute NPC
ClinicalTrials.gov Identifier: NCT03251196     History of Changes
Other Study ID Numbers: LMU-IMPH-TB Sequel-01
First Posted: August 16, 2017    Key Record Dates
Last Update Posted: February 6, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: To be shared amongst the Collaborators, on shared database when the study starts

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Tuberculosis
Respiratory Tract Infections
Tuberculosis, Pulmonary
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Infection
Respiratory Tract Diseases
Lung Diseases