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Trial record 82 of 103 for:    IVERMECTIN

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

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ClinicalTrials.gov Identifier: NCT03598842
Recruitment Status : Enrolling by invitation
First Posted : July 25, 2018
Last Update Posted : August 1, 2019
Sponsor:
Collaborators:
Rutgers, The State University of New Jersey
Jawaharlal Institute of Postgraduate Medical Education & Research
Information provided by (Responsible Party):
Boston Medical Center

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 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.

Condition or disease Intervention/treatment Phase
Tuberculosis Malnutrition Helminth Infection Dietary Supplement: Nutritional Supplementation Meal Dietary Supplement: Multivitamin Drug: Anti-parasitic medications Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Tuberculosis- Learning the Impact of Nutrition
Actual Study Start Date : July 12, 2019
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Dietary Supplement: Nutritional Supplementation Meal
Study participants will be given a nutritional supplementation for 6 months. The supplementation consists of a vegan meal plan.

Dietary Supplement: Multivitamin
Study participants will be given a daily multivitamin to take for 6 months.

Experimental: 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.
Dietary Supplement: Nutritional Supplementation Meal
Study participants will be given a nutritional supplementation for 6 months. The supplementation consists of a vegan meal plan.

Dietary Supplement: 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.
Other Name: albendazole, ivermectin, metronidazole

Active Comparator: 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.
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.
Other Name: albendazole, ivermectin, metronidazole

No Intervention: 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.



Primary Outcome Measures :
  1. Immune response [ Time Frame: Visit 1 ]
    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.

  2. Immune response [ Time Frame: Visit 2 (approximately 7 days after visit 1) ]
    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.

  3. Immune response [ Time Frame: Visit 5 (3 months after parasite treatment / intervention initiation) ]
    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.

  4. Immune Response [ Time Frame: Visit 6 (6 months after parasite treatment / intervention initiation) ]
    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.

  5. Immune Response [ Time Frame: Visit 7 (12 months after parasite treatment / intervention initiation) ]
    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 :
  1. Anthropometric measurement [ Time Frame: Visit 1 ]
    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.

  2. Anthropometric measurement [ Time Frame: Visit 5 (3 months after parasite treatment / intervention initiation) ]
    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.

  3. Anthropometric measurement [ Time Frame: Visit 6 (6 months after parasite treatment / intervention initiation) ]
    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.

  4. Anthropometric measurements [ Time Frame: Visit 7 (12 months after parasite treatment / intervention initiation) ]
    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.

  5. Anthropometric measurements [ Time Frame: Visit 8 (18 months after parasite treatment / intervention initiation) ]
    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.

  6. Anthropometric measurements [ Time Frame: Visit 9 (24 months after parasite treatment / intervention initiation) ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: Household Contacts

  • Household contact that has been roommate of eligible index case for at least two of the previous four months (See index case criteria below).
  • HIV seronegative
  • Willing to be tested for pregnancy
  • Age 18-55 years
  • Willingness by the patient to attend scheduled follow-up visits and undergo study assessments
  • Able to provide informed consent

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 HA1C
  • Xpert positive among those able to produce sputum
  • TB symptoms (night sweats, weight loss, cough)
  • 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.
  • Recall receiving anti-parasitic treatment within the past 6 months
  • Evidence of kwashiorkor (pitting edema of foot or lower leg)
  • Abnormal K, Mg, Phos in those with BMI <16

Inclusion Criteria: Index Case

  • Sputum Ziehl-Neelsen stain positive for 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 room during the previous four months
  • Agrees to have household contact notified about study

Exclusion Criteria: Index Case

  • No Xpert or culture confirmation and unable to provide sputum sample
  • No household contacts who share room
  • Known MDR or XDR TB case
  • BMI <16 kg/m2
  • Lower extremity edema/kwashiorkor
  • Reported neuropathy in lower extremities (may result from thiamine deficiency)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03598842


Locations
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India
Jawaharlal Institute of Postgraduate Medical Education and Research
Pondicherry, Tamil Nadu, India
Sponsors and Collaborators
Boston Medical Center
Rutgers, The State University of New Jersey
Jawaharlal Institute of Postgraduate Medical Education & Research
Investigators
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Principal Investigator: Natasha Hochberg, MD MPH Boston University

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Responsible Party: Boston Medical Center
ClinicalTrials.gov Identifier: NCT03598842     History of Changes
Other Study ID Numbers: H-37473
6005415 ( Other Grant/Funding Number: Warren Alpert Foundation )
First Posted: July 25, 2018    Key Record Dates
Last Update Posted: August 1, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Boston Medical Center:
blood signature of Tb risk
anti Mtb immunity
RNA biomarkers
RePORT Study
India
Additional relevant MeSH terms:
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Ivermectin
Tuberculosis
Helminthiasis
Malnutrition
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Nutrition Disorders
Parasitic Diseases
Metronidazole
Albendazole
Antiparasitic Agents
Anti-Infective Agents
Anti-Bacterial Agents
Antiprotozoal Agents
Anthelmintics
Anticestodal Agents
Antiplatyhelmintic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents