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Tuberculosis - Learning the Impact of Nutrition (TB-LION)

Primary Purpose

Tuberculosis, Malnutrition, Helminth Infection

Status
Active
Phase
Not Applicable
Locations
India
Study Type
Interventional
Intervention
Nutritional Supplementation Meal
Multivitamin
Anti-parasitic medications
Sponsored by
Boston Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Tuberculosis focused on measuring blood signature of Tb risk, anti Mtb immunity, RNA biomarkers, RePORT Study, India

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Jawaharlal Institute of Postgraduate Medical Education and Research

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Active Comparator

No Intervention

Arm Label

Malnourished without lung parasites

Malnourished with lung parasites

Well-nourished with lung parasites

Well-nourished without lung parasites

Arm Description

Thirty study participants, household contacts of an index TB case, who are malnourished and do not have lung parasites will be consented into the study intervention. The household contact and the rest of the household members will receive nutritional supplementation meals for six months. The family will receive the food in biweekly installments and will be given a vegan meal plan.The consented household contact will also receive a daily multivitamin.

Thirty study participants, household contacts of an index TB case, who are malnourished and have lung parasites will be consented into the study intervention. The household contact and the rest of the household members will receive nutritional supplementation meals for six months. The family will receive the food in biweekly installments and will be given a vegan meal plan. The consented household contact will also receive a daily multivitamin. These thirty study participants will be given anti-parasitic medications such as albendazole, ivermectin, metronidazole, or other medication per Indian guidelines to treat the parasite infection.

These thirty study participants will be given anti-parasitic medications such as albendazole, ivermectin, metronidazole, or other medication per Indian guidelines to treat the parasite infection.

These thirty study participants will serve as the control.These participants will be well-nourished and not have a parasite infection; therefore, they will not receive the nutritional supplementation or treatment for parasite infection.

Outcomes

Primary Outcome Measures

Immune response
Interferon Gamma-peripheral blood mononuclear cell (PBMC) from malnourished and well-nourished household contacts (HHC) will be labeled with carboxyfluorescein succinimidyl ester (CFSE) and then stimulated with early secreted antigen target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) peptide libraries. After 72 hours, supernatants will be harvested and the cells analyzed by flow cytometry to monitor proliferating cells. As CFSE concentrations in a cell are halved with every cell division, each generation of cells appears as a distinct peak on the flow cytometry histogram providing a proliferative index. Supernatants will be evaluated by multiplex ELISA.
Immune response
Interferon Gamma - PBMC from malnourished and well-nourished HHC will be labeled with carboxyfluorescein succinimidyl ester (CFSE) and then stimulated with ESAT-6 and CFP-10 peptide libraries. After 72 hours, supernatants will be harvested and the cells analyzed by flow cytometry to monitor proliferating cells. As CFSE concentrations in a cell are halved with every cell division, each generation of cells appears as a distinct peak on the flow cytometry histogram providing a proliferative index. Supernatants will be evaluated by multiplex ELISA.
Immune response
Interferon Gamma - PBMC from malnourished and well-nourished HHC will be labeled with carboxyfluorescein succinimidyl ester (CFSE) and then stimulated with ESAT-6 and CFP-10 peptide libraries. After 72 hours, supernatants will be harvested and the cells analyzed by flow cytometry to monitor proliferating cells. As CFSE concentrations in a cell are halved with every cell division, each generation of cells appears as a distinct peak on the flow cytometry histogram providing a proliferative index. Supernatants will be evaluated by multiplex ELISA.
Immune Response
Interferon Gamma - PBMC from malnourished and well-nourished HHC will be labeled with carboxyfluorescein succinimidyl ester (CFSE) and then stimulated with ESAT-6 and CFP-10 peptide libraries. After 72 hours, supernatants will be harvested and the cells analyzed by flow cytometry to monitor proliferating cells. As CFSE concentrations in a cell are halved with every cell division, each generation of cells appears as a distinct peak on the flow cytometry histogram providing a proliferative index. Supernatants will be evaluated by multiplex ELISA.
Immune Response
Interferon Gamma - PBMC from malnourished and well-nourished HHC will be labeled with carboxyfluorescein succinimidyl ester (CFSE) and then stimulated with ESAT-6 and CFP-10 peptide libraries. After 72 hours, supernatants will be harvested and the cells analyzed by flow cytometry to monitor proliferating cells. As CFSE concentrations in a cell are halved with every cell division, each generation of cells appears as a distinct peak on the flow cytometry histogram providing a proliferative index. Supernatants will be evaluated by multiplex ELISA.

Secondary Outcome Measures

Anthropometric measurement
Body Mass Index - (BMI; weight/height in kg/m2). Measurements will be taken in triplicate. Height will be measured to the nearest 0.5 cm with a stadiometer (or knee height, ulnar length or arm span [demispan] for those persons unable to stand fully erect); body weight will be measured to the nearest 0.1 kg.
Anthropometric measurement
Body Mass Index - (BMI; weight/height in kg/m2). Measurements will be taken in triplicate. Height will be measured to the nearest 0.5 cm with a stadiometer (or knee height, ulnar length or arm span [demispan] for those persons unable to stand fully erect); body weight will be measured to the nearest 0.1 kg.
Anthropometric measurement
Body Mass Index - (BMI; weight/height in kg/m2). Measurements will be taken in triplicate. Height will be measured to the nearest 0.5 cm with a stadiometer (or knee height, ulnar length or arm span [demispan] for those persons unable to stand fully erect); body weight will be measured to the nearest 0.1 kg.
Anthropometric measurements
Body Mass Index - (BMI; weight/height in kg/m2). Measurements will be taken in triplicate. Height will be measured to the nearest 0.5 cm with a stadiometer (or knee height, ulnar length or arm span [demispan] for those persons unable to stand fully erect); body weight will be measured to the nearest 0.1 kg.
Anthropometric measurements
Body Mass Index - (BMI; weight/height in kg/m2). Measurements will be taken in triplicate. Height will be measured to the nearest 0.5 cm with a stadiometer (or knee height, ulnar length or arm span [demispan] for those persons unable to stand fully erect); body weight will be measured to the nearest 0.1 kg.
Anthropometric measurements
Body Mass Index - (BMI; weight/height in kg/m2). Measurements will be taken in triplicate. Height will be measured to the nearest 0.5 cm with a stadiometer (or knee height, ulnar length or arm span [demispan] for those persons unable to stand fully erect); body weight will be measured to the nearest 0.1 kg.

Full Information

First Posted
July 16, 2018
Last Updated
September 12, 2023
Sponsor
Boston Medical Center
Collaborators
Rutgers, The State University of New Jersey, Jawaharlal Institute of Postgraduate Medical Education & Research
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1. Study Identification

Unique Protocol Identification Number
NCT03598842
Brief Title
Tuberculosis - Learning the Impact of Nutrition
Acronym
TB-LION
Official Title
Tuberculosis- Learning the Impact of Nutrition
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 12, 2019 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boston Medical Center
Collaborators
Rutgers, The State University of New Jersey, Jawaharlal Institute of Postgraduate Medical Education & Research

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis, Malnutrition, Helminth Infection
Keywords
blood signature of Tb risk, anti Mtb immunity, RNA biomarkers, RePORT Study, India

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
123 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Malnourished without lung parasites
Arm Type
Experimental
Arm Description
Thirty study participants, household contacts of an index TB case, who are malnourished and do not have lung parasites will be consented into the study intervention. The household contact and the rest of the household members will receive nutritional supplementation meals for six months. The family will receive the food in biweekly installments and will be given a vegan meal plan.The consented household contact will also receive a daily multivitamin.
Arm Title
Malnourished with lung parasites
Arm Type
Experimental
Arm Description
Thirty study participants, household contacts of an index TB case, who are malnourished and have lung parasites will be consented into the study intervention. The household contact and the rest of the household members will receive nutritional supplementation meals for six months. The family will receive the food in biweekly installments and will be given a vegan meal plan. The consented household contact will also receive a daily multivitamin. These thirty study participants will be given anti-parasitic medications such as albendazole, ivermectin, metronidazole, or other medication per Indian guidelines to treat the parasite infection.
Arm Title
Well-nourished with lung parasites
Arm Type
Active Comparator
Arm Description
These thirty study participants will be given anti-parasitic medications such as albendazole, ivermectin, metronidazole, or other medication per Indian guidelines to treat the parasite infection.
Arm Title
Well-nourished without lung parasites
Arm Type
No Intervention
Arm Description
These thirty study participants will serve as the control.These participants will be well-nourished and not have a parasite infection; therefore, they will not receive the nutritional supplementation or treatment for parasite infection.
Intervention Type
Dietary Supplement
Intervention Name(s)
Nutritional Supplementation Meal
Intervention Description
Study participants will be given a nutritional supplementation for 6 months. The supplementation consists of a vegan meal plan.
Intervention Type
Dietary Supplement
Intervention Name(s)
Multivitamin
Intervention Description
Study participants will be given a daily multivitamin to take for 6 months.
Intervention Type
Drug
Intervention Name(s)
Anti-parasitic medications
Other Intervention Name(s)
albendazole, ivermectin, metronidazole
Intervention Description
Study participants will be given anti-parasitic medications per Indian guidelines such as albendazole, ivermectin, metronidazole, or other medications to treat their parasitic infection.
Primary Outcome Measure Information:
Title
Immune response
Description
Interferon Gamma-peripheral blood mononuclear cell (PBMC) from malnourished and well-nourished household contacts (HHC) will be labeled with carboxyfluorescein succinimidyl ester (CFSE) and then stimulated with early secreted antigen target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) peptide libraries. After 72 hours, supernatants will be harvested and the cells analyzed by flow cytometry to monitor proliferating cells. As CFSE concentrations in a cell are halved with every cell division, each generation of cells appears as a distinct peak on the flow cytometry histogram providing a proliferative index. Supernatants will be evaluated by multiplex ELISA.
Time Frame
Visit 1
Title
Immune response
Description
Interferon Gamma - PBMC from malnourished and well-nourished HHC will be labeled with carboxyfluorescein succinimidyl ester (CFSE) and then stimulated with ESAT-6 and CFP-10 peptide libraries. After 72 hours, supernatants will be harvested and the cells analyzed by flow cytometry to monitor proliferating cells. As CFSE concentrations in a cell are halved with every cell division, each generation of cells appears as a distinct peak on the flow cytometry histogram providing a proliferative index. Supernatants will be evaluated by multiplex ELISA.
Time Frame
Visit 2 (approximately 7 days after visit 1)
Title
Immune response
Description
Interferon Gamma - PBMC from malnourished and well-nourished HHC will be labeled with carboxyfluorescein succinimidyl ester (CFSE) and then stimulated with ESAT-6 and CFP-10 peptide libraries. After 72 hours, supernatants will be harvested and the cells analyzed by flow cytometry to monitor proliferating cells. As CFSE concentrations in a cell are halved with every cell division, each generation of cells appears as a distinct peak on the flow cytometry histogram providing a proliferative index. Supernatants will be evaluated by multiplex ELISA.
Time Frame
Visit 5 (3 months after parasite treatment / intervention initiation)
Title
Immune Response
Description
Interferon Gamma - PBMC from malnourished and well-nourished HHC will be labeled with carboxyfluorescein succinimidyl ester (CFSE) and then stimulated with ESAT-6 and CFP-10 peptide libraries. After 72 hours, supernatants will be harvested and the cells analyzed by flow cytometry to monitor proliferating cells. As CFSE concentrations in a cell are halved with every cell division, each generation of cells appears as a distinct peak on the flow cytometry histogram providing a proliferative index. Supernatants will be evaluated by multiplex ELISA.
Time Frame
Visit 6 (6 months after parasite treatment / intervention initiation)
Title
Immune Response
Description
Interferon Gamma - PBMC from malnourished and well-nourished HHC will be labeled with carboxyfluorescein succinimidyl ester (CFSE) and then stimulated with ESAT-6 and CFP-10 peptide libraries. After 72 hours, supernatants will be harvested and the cells analyzed by flow cytometry to monitor proliferating cells. As CFSE concentrations in a cell are halved with every cell division, each generation of cells appears as a distinct peak on the flow cytometry histogram providing a proliferative index. Supernatants will be evaluated by multiplex ELISA.
Time Frame
Visit 7 (12 months after parasite treatment / intervention initiation)
Secondary Outcome Measure Information:
Title
Anthropometric measurement
Description
Body Mass Index - (BMI; weight/height in kg/m2). Measurements will be taken in triplicate. Height will be measured to the nearest 0.5 cm with a stadiometer (or knee height, ulnar length or arm span [demispan] for those persons unable to stand fully erect); body weight will be measured to the nearest 0.1 kg.
Time Frame
Visit 1
Title
Anthropometric measurement
Description
Body Mass Index - (BMI; weight/height in kg/m2). Measurements will be taken in triplicate. Height will be measured to the nearest 0.5 cm with a stadiometer (or knee height, ulnar length or arm span [demispan] for those persons unable to stand fully erect); body weight will be measured to the nearest 0.1 kg.
Time Frame
Visit 5 (3 months after parasite treatment / intervention initiation)
Title
Anthropometric measurement
Description
Body Mass Index - (BMI; weight/height in kg/m2). Measurements will be taken in triplicate. Height will be measured to the nearest 0.5 cm with a stadiometer (or knee height, ulnar length or arm span [demispan] for those persons unable to stand fully erect); body weight will be measured to the nearest 0.1 kg.
Time Frame
Visit 6 (6 months after parasite treatment / intervention initiation)
Title
Anthropometric measurements
Description
Body Mass Index - (BMI; weight/height in kg/m2). Measurements will be taken in triplicate. Height will be measured to the nearest 0.5 cm with a stadiometer (or knee height, ulnar length or arm span [demispan] for those persons unable to stand fully erect); body weight will be measured to the nearest 0.1 kg.
Time Frame
Visit 7 (12 months after parasite treatment / intervention initiation)
Title
Anthropometric measurements
Description
Body Mass Index - (BMI; weight/height in kg/m2). Measurements will be taken in triplicate. Height will be measured to the nearest 0.5 cm with a stadiometer (or knee height, ulnar length or arm span [demispan] for those persons unable to stand fully erect); body weight will be measured to the nearest 0.1 kg.
Time Frame
Visit 8 (18 months after parasite treatment / intervention initiation)
Title
Anthropometric measurements
Description
Body Mass Index - (BMI; weight/height in kg/m2). Measurements will be taken in triplicate. Height will be measured to the nearest 0.5 cm with a stadiometer (or knee height, ulnar length or arm span [demispan] for those persons unable to stand fully erect); body weight will be measured to the nearest 0.1 kg.
Time Frame
Visit 9 (24 months after parasite treatment / intervention initiation)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pranay Sinha, MD
Organizational Affiliation
Boston University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Jawaharlal Institute of Postgraduate Medical Education and Research
City
Pondicherry
State/Province
Tamil Nadu
Country
India

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34641820
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.
Results Reference
derived

Learn more about this trial

Tuberculosis - Learning the Impact of Nutrition

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