Clinical trial NCT04985994: Potential Role of Microbiome in Tuberculosis
Official title: Exploring the Role of Microbiome in Susceptibility, Treatment Response and Outcome Among Tuberculosis Patients; a Prospective Cohort Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Tuberculosis
Keywords: Tuberculosis
Pulmonary TB
Microbiome
Immunity
Nutrition
Treatment response
Treatment Outcome
Gut microbiome
Oral Microbiome
Inflammation
Dietary intake
Lead sponsor: Khyber Medical University Peshawar
Sponsor class: OTHER
Collaborators: name: University of Reading
name: TB Control Program Khyber Pakhtunkhwa
First posted: 2021-08-02
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study will be conducted primarily in three district levels (Peshawar, Mardan and Swat) TB diagnostic and treatment centers of Khyber Pakhtunkhwa province of Pakistan. These centers have been selected based on the highest TB prevalence in the year 2020

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Gut microbiome diversity and functional potential
timeFrame: 2 Years
Secondary outcomes:
measure: Baseline Gut microbiome
timeFrame: 1 year
measure: Baseline Oral microbiome
timeFrame: 1 year
measure: Gut microbiome and associated factors
timeFrame: 1 year
measure: Microbial dysbiosis
timeFrame: Two years
measure: Microbial signatures
timeFrame: 2 years
Other outcomes:
Locations:
city: Peshawar
country: Pakistan
facility: DTO Peshawar
state: KP
city: Peshawar
country: Pakistan
facility: Khyber Medical University
state: KP
Study officials:
affiliation: Khyber Medical University
name: Muhammad Shahzad
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shahzad M, Andrews SC, Ul-Haq Z. Exploring the role of Microbiome in Susceptibility, Treatment Response and Outcome among Tuberculosis Patients from Pakistan: study protocol for a prospective cohort study (Micro-STOP). BMJ Open. 2022 Jun 7;12(6):e058463. doi: 10.1136/bmjopen-2021-058463.