Micro-STOP: Potential Role of Microbiome in Tuberculosis

Sponsor

Khyber Medical University Peshawar (Other)

Overall Status

Recruiting

CT.gov ID

NCT04985994

Collaborator

University of Reading (Other), TB Control Program Khyber Pakhtunkhwa (Other)

450

Enrollment

Locations

23.5

Anticipated Duration (Months)

225

Patients Per Site

9.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a deadly infectious disease and major global public health problem. Recent evidence from animal studies suggests that the microbiome plays a role in TB pathogenesis and immune response. However, until now, no similar study has been performed in humans and thus any influence of the microbiota on TB or vice versa remains unknown.

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis

Detailed Description

Tuberculosis is among one of the most difficult to treat infections that require multidrug therapy for prolonged periods, in most cases 6-9 months. Treatment failure is still common and frequently observed (even where adherence to antibiotic therapy is maintained) in 15% of drug-susceptible infections and 31% for drug-resistant cases. Although poor patient compliance and the emergence of drug-resistant Mtb strains are generally implicated as a major cause of TB treatment failure, other factors such as the role of the microbiome in TB pathogenesis and reactivation are poorly considered.

The human microbiome is a consortium/collection of all microorganisms (bacteria, archaea, viruses, and fungi) colonizing different habitats in the human body such as skin, gut, and mucosal surfaces and living in a commensal relationship with each other. Emerging evidence suggests a crucial role of the microbiome in hosts physiology, nutritional status, and development of the functional immune system. Microbial dysbiosis is the change in microbial composition or functional potential that has been implicated both in infectious diseases status as well as the development of non-communicable disease in hosts ranging from immune mediated diseases to intergenerational obesity and even cancers. Microbial dysbiosis at different body sites has also been reported in TB-associated comorbidities such as diabetes mellitus and malnutrition. However, to date, the role of the microbiome and microbial dysbiosis is not clear in the context of TB infections in humans.

Therefore, this study aims to dissect the relationship between the microbiomes and its interaction with the immune system during TB infection, and anti-tuberculosis therapy in humans.

Study Design

Study Type:

Observational

Anticipated Enrollment :

450 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Exploring the Role of Microbiome in Susceptibility, Treatment Response and Outcome Among Tuberculosis Patients; a Prospective Cohort Study

Actual Study Start Date :

Aug 22, 2021

Anticipated Primary Completion Date :

Aug 8, 2022

Anticipated Study Completion Date :

Aug 8, 2023

Arms and Interventions

Arm	Intervention/Treatment
Tuberculosis Patients Diagnosed with pulmonary TB after detailed history collection, clinical examination, and laboratory assessment (sputum culture positive). Aged 18 years or above. Willing to participate in the study.
Healthy Volunteers Healthy subjects with no symptoms or history of pulmonary TB Negative sputum culture Matched for sex and age (±5 years) with the TB patient group.

Outcome Measures

Primary Outcome Measures

Gut microbiome diversity and functional potential [2 Years]
To explore the effect of TB infection and anti-tuberculosis therapy on gut microbiome diversity, functional potential and immune response in newly diagnosed TB patients from Pakistan.

Secondary Outcome Measures

Baseline Gut microbiome [1 year]
To determine gut microbiome diversity and functional potential at baseline and compare with healthy controls
Baseline Oral microbiome [1 year]
To determine oral microbiome diversity and functional potential at baseline and compare with healthy controls
Gut microbiome and associated factors [1 year]
3. To assess the relationship between gut microbiome and socio-demographic characteristics and dietary intake in TB patients at baseline, before the start of anti-tuberculosis treatment.
Microbial dysbiosis [Two years]
To describe the occurrence of gut microbial dysbiosis and its association with adverse reaction and treatment failure in TB patients.
Microbial signatures [2 years]
5. To identify specific oral and gut enterotypes associated with adverse reaction and unfavorable treatment outcomes.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Diagnosed with TB after detailed history collection, clinical examination and laboratory assessment (sputum culture positive).
Aged 18 - 65 years.
Willing to participate in the study.
Healthy controls are those who are free of TB symptoms, healthy on physical examination and with a negative sputum culture result.

Exclusion Criteria:

Already on anti-TB treatment or previously treated for TB.
Severely anemic (Hb < 10g/dL).
Having diarrhea or other major gastrointestinal disorders.
Using or have used aminoglycoside or quinolones antibiotics in the past one month.
Using a medically prescribed diet or nutrition supplement.
Pregnant or lactating women.
Patients with liver or renal dysfunction, or having any other chronic disease condition.
Multidrug resistance TB patients