Potential Role of Microbiome in Tuberculosis

Tuberculosis Clinical Trial

— Micro-STOP  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04985994
• Other study ID #: Microbiome & Tuberculosis
• Secondary ID: 10289/KPK/NRPU/R
• Status: Recruiting
• Start date: August 22, 2021
• Est. completion date: August 31, 2024

Study information

• Verified date: October 2023
• Source: Khyber Medical University Peshawar
• Contact: Muhammad Shahzad, PhD
• Phone: +92-345-9048796
• Email: shahzad.ibms[@]kmu.edu.pk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 450
• Est. completion date: August 31, 2024
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Diagnosed with TB after detailed history collection, clinical examination and laboratory assessment (sputum culture positive).

2. Aged 18 - 65 years.

3. Willing to participate in the study.

4. Healthy controls are those who are free of TB symptoms, healthy on physical examination and with a negative sputum culture result.

Exclusion Criteria:

1. Already on anti-TB treatment or previously treated for TB.

2. Severely anemic (Hb < 10g/dL).

3. Having diarrhea or other major gastrointestinal disorders.

4. Using or have used aminoglycoside or quinolones antibiotics in the past one month.

5. Using a medically prescribed diet or nutrition supplement.

6. Pregnant or lactating women.

7. Patients with liver or renal dysfunction, or having any other chronic disease condition.

8. Multidrug resistance TB patients

Related Conditions & MeSH terms

• Tuberculosis

Locations

Country	Name	City	State
Pakistan	DTO Peshawar	Peshawar	KP
Pakistan	Khyber Medical University	Peshawar	KP

Sponsors (3)

Lead Sponsor	Collaborator
Khyber Medical University Peshawar	TB Control Program Khyber Pakhtunkhwa, University of Reading

Country where clinical trial is conducted

Pakistan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gut microbiome diversity and functional potential	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.	2 Years
Secondary	Baseline Gut microbiome	To determine gut microbiome diversity and functional potential at baseline and compare with healthy controls	1 year
Secondary	Baseline Oral microbiome	To determine oral microbiome diversity and functional potential at baseline and compare with healthy controls	1 year
Secondary	Gut microbiome and associated factors	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.	1 year
Secondary	Microbial dysbiosis	To describe the occurrence of gut microbial dysbiosis and its association with adverse reaction and treatment failure in TB patients.	Two years
Secondary	Microbial signatures	5. To identify specific oral and gut enterotypes associated with adverse reaction and unfavorable treatment outcomes.	2 years