TB Nutrition, Immunology and Epidemiology
Condition: Mycobacterium Tuberculosis
MeSH terms: Tuberculosis
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to see whether people who take vitamins along with the standard
      medicine for tuberculosis (TB) recover better and quicker than people who take only the
      standard medicine for TB. This study will enroll 600 men and women, who are age 18-65 years,
      have TB, and intend to stay in Dar-es-Salaam for at least 2 years from the start of TB
      therapy. Half the participants will have active TB and also HIV infection, and the other half
      will have TB alone. Half the volunteers will be given vitamins, and the other half will be
      given placebo (sugar pill with no vitamins) from the start of their TB therapy, through the 8
      months of anti-TB therapy, and up to 48 months. Participation in the study involves visits to
      the clinic, physical exams, home visits, and answering questions about personal health, foods
      eaten, household, occupation, and education. Volunteers will also provide blood, sputum, and
      urine samples.
    

Detailed description: 
      This double blinded, randomized, placebo controlled trial will enroll 600 men and women, who
      are age 18 to 65 years inclusive, have at least two positive sputum smears for tuberculosis
      (TB), intend to stay in Dar-es-Salaam (DSM) for at least 2 years from the start of TB
      therapy, and have given informed consent to participate in the study. Half of the enrollees
      will have active TB and co-infection with HIV, and the other half will have TB alone. The
      effect of micronutrient status will be examined in the context of a randomized trial
      conducted in Tanzania. Subjects will be randomized to receive either multi-micronutrients or
      placebo from the start of their TB therapy, through the 8 months of anti-TB therapy, and
      until the last recruited patient reaches 24 months of follow up. Thus, the first subject is
      likely to be followed for 48 months, assuming the duration of recruitment is 24 months. The
      endpoints of interest include bacteriologic cure, immune response parameters, and clinical
      outcomes. The researchers will also examine the utility of these immune response parameters
      as surrogate markers for treatment efficacy in TB, irrespective of nutritional and other risk
      factors. The study will be carried out as a collaborative effort between Harvard School of
      Public Health; Muhimbili University College of Health Sciences, Dar es Salaam, Tanzania;
      Tufts University, Boston; and the Channing Laboratory, Boston. Subjects will be randomly
      assigned to receive a daily oral dose of one of two treatments: (a) micronutrients: 5000 IU
      of retinol, 20 mg of B1, 20 mg of B2, 25 mg of B6, 100 mg of niacin, 50 mcg of B12, 500 of C,
      200 mg of E, 0.8 mg of folic acid, and 100 mcg of selenium; or (b) placebo. The primary
      objectives are to: (1) determine the efficacy of micronutrient supplements on sputum and
      culture negativity at one month and two months; (2) determine the efficacy of micronutrient
      supplements on survival between two arms at 8 and 24 months; and (3) determine the efficacy
      of micronutrient supplements on TB relapse and reinfection. Secondary study objectives are
      to: (1) compare the treatment arms with respect to rate of change of HIV viral load in HIV
      positive subjects measured at 0, 2, 8, and 20 months; (2) compare the treatment arms with
      respect to absolute change in CD4 counts from 0 to 2, 8, 20 months; (3) compare the treatment
      arms with respect to weight change from baseline and 2 months, 8 months, and 20 months; (4)
      compare the treatment arms with respect to immunological parameters, namely ex vivo
      lymphocyte proliferation; and cytokine production, namely IL-2, INF-g, IL-12, and TNF-a, at
      2, 8, 20 months; and (5) correlate the above mentioned immunological markers with smear
      conversion rates at 1 month, 2 months, cure, relapse, and death.
    

Intervention name(s): Folic Acid; Micronutrients: Vitamins B1, B2, B6, Niacin, B12, C, E.; Selenium; Vitamin A
Intervention type(s): Drug; Drug; Drug; Drug
Intervention MeSH terms: Vitamins; Folic Acid; Vitamin A; Thiamine; Selenium; Micronutrients; Trace Elements
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: HIV Infections, Tuberculosis, Malnutrition, Tanzania