Tuberculosis - Learning the Impact of Nutrition

NCT ID: NCT03598842

Last Updated: 2026-01-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 786 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-12
• Study Completion Date: 2025-12-29

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.

Conditions

Tuberculosis; Malnutrition; Helminth Infection

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Malnourished without lung parasites

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.

Group Type: EXPERIMENTAL

Nutritional Supplementation Meal

Intervention Type: DIETARY_SUPPLEMENT

Study participants will be given a nutritional supplementation for 6 months. The supplementation consists of a vegan meal plan.

Multivitamin

Intervention Type: DIETARY_SUPPLEMENT

Study participants will be given a daily multivitamin to take for 6 months.

Malnourished with lung parasites

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.

Group Type: EXPERIMENTAL

Nutritional Supplementation Meal

Intervention Type: DIETARY_SUPPLEMENT

Study participants will be given a nutritional supplementation for 6 months. The supplementation consists of a vegan meal plan.

Multivitamin

Intervention Type: DIETARY_SUPPLEMENT

Study participants will be given a daily multivitamin to take for 6 months.

Anti-parasitic medications

Intervention Type: DRUG

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

Well-nourished with lung parasites

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.

Group Type: ACTIVE_COMPARATOR

Anti-parasitic medications

Intervention Type: DRUG

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

Well-nourished without lung parasites

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Nutritional Supplementation Meal

Study participants will be given a nutritional supplementation for 6 months. The supplementation consists of a vegan meal plan.

Intervention Type: DIETARY_SUPPLEMENT

Multivitamin

Study participants will be given a daily multivitamin to take for 6 months.

Intervention Type: DIETARY_SUPPLEMENT

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.

Intervention Type: DRUG

Other Intervention Names

albendazole, ivermectin, metronidazole

Eligibility Criteria

Inclusion Criteria

• 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.

• 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

• 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

• 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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rutgers, The State University of New Jersey

OTHER

Sponsor Role: collaborator

Jawaharlal Institute of Postgraduate Medical Education & Research

OTHER_GOV

Sponsor Role: collaborator

Boston Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pranay Sinha, MD

Role: PRINCIPAL_INVESTIGATOR

Boston University

Locations

Jawaharlal Institute of Postgraduate Medical Education and Research

Pondicherry, Tamil Nadu, India

Countries

India

References

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.

Reference Type: DERIVED

PMID: 34641820 (View on PubMed)

Other Identifiers

6005415

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

H-37473

Identifier Type: -

Identifier Source: org_study_id