Clinical trial NCT03598842: Tuberculosis - Learning the Impact of Nutrition
Official title: Tuberculosis- Learning the Impact of Nutrition
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Tuberculosis
Malnutrition
Helminth Infection
Keywords: blood signature of Tb risk
anti Mtb immunity
RNA biomarkers
RePORT Study
India
Lead sponsor: Boston Medical Center
Sponsor class: OTHER
Collaborators: name: Rutgers, The State University of New Jersey
name: Jawaharlal Institute of Postgraduate Medical Education & Research
First posted: 2018-07-26
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The proposed work is based on the finding that one-third of the world is infected with the bacteria Mycobacterium tuberculosis (Mtb) and only 10% of these individuals develop TB. The study aims to identify factors that drive progression to disease and study signals (markers of the immune response) that detect who will progress to active TB and why this happens. Armed with these markers, the study will address how malnutrition and worms alter this signal profile to cause active TB. The work will be conducted in India, where there are 2.8 million TB cases each year - more than any other country - and where the government has committed to eliminating TB by 2035. Data suggest that malnutrition and parasites increase risk of TB disease so the investigators will feed malnourished household contacts and have those with parasites receive medication to treat these. Using this infrastructure, the investigators will evaluate the immunologic impact of feeding on TB pathogenesis. An additional aim is to understand the role of parasitic worms with the goal of determining the utility of low-cost ($.02 per dose) worm treatment as part of TB control efforts. Risk of developing TB will be evaluated for 120 household contacts of TB patients in the setting of their malnutrition and parasites. There are four study arms comprised of thirty participants each -- malnourished with parasite infection, malnourished with no parasite infection, well-nourished with parasite infection, and well-nourished with no parasite infection. Correlates of risk of disease will be assessed using blood messenger RNA/micro RNA (mRNA/miRNA) sequencing and T cell immune markers. The TB LION study will confirm that malnutrition and worms increase the risk of active TB and will provide the basis for effective interventions that could change the face of the TB pandemic and have a profound impact on the health of people worldwide. Participants in this study will be household contacts of tuberculosis index cases. The index cases in this study do not participate in the study once a household contact is established. All interventions and follow up are only being conducted within the household contact cohort. All intervention supplies, treatments, and biologics will be purchased internationally.


Eligibility criteria: Inclusion Criteria: Household Contacts

* Household contact that has been housemate of eligible index case for at least the last month (See index case criteria below).
* HIV seronegative
* Willing to be tested for pregnancy if married
* Age 18-60 years
* Willingness by the patient to attend scheduled follow-up visits and undergo study assessments
* Able to provide informed consent
* Intervention inclusion: On average, one meal consumed at home per day.

Exclusion Criteria: Household Contacts

* In the team's judgement, individual is not expected to survive for 12 months
* HIV infection or not willing to undergo HIV testing (if no documented HIV test)
* Pregnant at enrollment
* Known diabetes mellitus or evidence of diabetes on hemoglobin A1C (HA1C)
* Xpert positive among those able to produce sputum
* TB symptoms (night sweats, weight loss, cough) - Only if sputum positive
* Any history of TB disease during their lifetime
* We will retrospectively exclude household contacts of presumed TB cases whose cultures do not confirm Mtb or who are Xpert negative.
* Evidence of kwashiorkor (pitting edema of foot or lower leg) those with BMI \<16
* Abnormal K, Mg, Phos in those with BMI \<16

Inclusion Criteria: Index Case

* Sputum Ziehl-Neelsen stain positive for acid-fast bacillus (AFB) ≥1+
* Culture or Xpert positive for Mtb; those who are smear+ but ultimately Xpert or culture negative, will be included until their culture results return at which time they will retrospectively be removed from the study.
* No history of TB treatment (i.e., no history of partial or complete treatment for a previous TB episode)
* Has at least 1 household contact with whom they have shared a house during the previous one month
* Agrees to have household contact notified about study

Exclusion Criteria: Index Case

* Pregnant at enrollment
* No Xpert or culture confirmation and unable to provide sputum sample
* No household contacts who share room
* Known Multidrug-resistant tuberculosis (MDR-TB) or extensively drug-resistant tuberculosis (XDR-TB) case
* BMI \<14 kg/m2
* Abnormal K, Mg, Phos in those with BMI 14 - 16
* Lower extremity edema/kwashiorkor those with BMI 14-16
* Reported neuropathy in lower extremities (may result from thiamine deficiency)

Primary outcomes:
measure: Immune response
timeFrame: Visit 1
measure: Immune response
timeFrame: Visit 2 (approximately 7 days after visit 1)
measure: Immune response
timeFrame: Visit 5 (3 months after parasite treatment / intervention initiation)
measure: Immune Response
timeFrame: Visit 6 (6 months after parasite treatment / intervention initiation)
measure: Immune Response
timeFrame: Visit 7 (12 months after parasite treatment / intervention initiation)
Secondary outcomes:
measure: Anthropometric measurement
timeFrame: Visit 1
measure: Anthropometric measurement
timeFrame: Visit 5 (3 months after parasite treatment / intervention initiation)
measure: Anthropometric measurement
timeFrame: Visit 6 (6 months after parasite treatment / intervention initiation)
measure: Anthropometric measurements
timeFrame: Visit 7 (12 months after parasite treatment / intervention initiation)
measure: Anthropometric measurements
timeFrame: Visit 8 (18 months after parasite treatment / intervention initiation)
measure: Anthropometric measurements
timeFrame: Visit 9 (24 months after parasite treatment / intervention initiation)
Other outcomes:
Locations:
city: Pondicherry
country: India
facility: Jawaharlal Institute of Postgraduate Medical Education and Research
state: Tamil Nadu
Study officials:
affiliation: Boston University
name: Pranay Sinha, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cintron C, Narasimhan PB, Locks L, Babu S, Sinha P, Rajkumari N, Kaipilyawar V, Bhargava A, Maloomian K, Chandrasekaran P, Verma S, Joseph N, Johnson WE, Wanke C, Horsburgh CR Jr, Ellner JJ, Sarkar S, Salgame P, Lakshminarayanan S, Hochberg NS. Tuberculosis-Learning the Impact of Nutrition (TB LION): protocol for an interventional study to decrease TB risk in household contacts. BMC Infect Dis. 2021 Oct 12;21(1):1058. doi: 10.1186/s12879-021-06734-z.