Tuberculosis - Learning the Impact of Nutrition

Tuberculosis Clinical Trial

— TB-LION  

Official title:

Tuberculosis- Learning the Impact of Nutrition

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03598842
• Other study ID #: H-37473
• Secondary ID: 6005415
• Status: Active, not recruiting
• Phase: N/A
• Start date: July 12, 2019
• Est. completion date: December 2025

Study information

• Verified date: September 2023
• Source: Boston Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 123
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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)

Related Conditions & MeSH terms

• Helminth Infection
• Helminthiasis
• Malnutrition
• Tuberculosis

Intervention

Dietary Supplement:
• Nutritional Supplementation Meal
Study participants will be given a nutritional supplementation for 6 months. The supplementation consists of a vegan meal plan.
• Multivitamin
Study participants will be given a daily multivitamin to take for 6 months.

Drug:
• Anti-parasitic medications
Study participants will be given anti-parasitic medications per Indian guidelines such as albendazole, ivermectin, metronidazole, or other medications to treat their parasitic infection.

Locations

Country	Name	City	State
India	Jawaharlal Institute of Postgraduate Medical Education and Research	Pondicherry	Tamil Nadu

Sponsors (3)

Lead Sponsor	Collaborator
Boston Medical Center	Jawaharlal Institute of Postgraduate Medical Education & Research, Rutgers, The State University of New Jersey

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Visit 1
Primary	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.	Visit 2 (approximately 7 days after visit 1)
Primary	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.	Visit 5 (3 months after parasite treatment / intervention initiation)
Primary	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.	Visit 6 (6 months after parasite treatment / intervention initiation)
Primary	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.	Visit 7 (12 months after parasite treatment / intervention initiation)
Secondary	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.	Visit 1
Secondary	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.	Visit 5 (3 months after parasite treatment / intervention initiation)
Secondary	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.	Visit 6 (6 months after parasite treatment / intervention initiation)
Secondary	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.	Visit 7 (12 months after parasite treatment / intervention initiation)
Secondary	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.	Visit 8 (18 months after parasite treatment / intervention initiation)
Secondary	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.	Visit 9 (24 months after parasite treatment / intervention initiation)