Impact of Vitamin D Supplementation on Host Immunity to Mycobacterium Tuberculosis and Response to Treatment

This is a double-blind, randomized, controlled clinical trial on the clinical efficacy and antimicrobial mechanisms of oral high dose vitamin D3 therapy three times weekly given for 8 weeks followed by the same vitamin D dose given every other week for a subsequent 8 weeks (n=129) versus placebo (n=129) in newly diagnosed Georgian patients with pulmonary TB.

The trial is also designed to obtain needed information on vitamin D status and general nutritional status in TB patients in Georgia, explore vitamin D regulation of the endogenous antimicrobial peptide cathelicidin/LL-37 in human tissues, and obtain hypothesis-generating data on the potential role of cathelicidin/LL-37 as a mechanism for the anti-mycobacterial effects of vitamin D in humans.

The potential study subjects will be identified and clinically monitored by clinical study coordinators after diagnosis by standard methods (compatible signs and symptoms, positive sputum AFB smear and culture, chest X-ray). Medical records of all patients with newly diagnosed tuberculosis registered for treatment at the NCTBLD in Tbilisi will be screened for eligibility for participation in the study. Written informed consent will be obtained from patients who met eligibility criteria and agreed to participate in the study prior to the subject undergoing any study-related procedure. Participation in study will involve a total of seven study visits (one baseline and six follow up visits.

TB patients will otherwise be conventionally treated with anti-TB drug regimens using the DOTS protocols: an initial 2 month in-hospital intensive phase with daily treatment with oral rifampicin, isoniazid, pyrazinamide and ethambutol, followed by an outpatient continuation phase for 4 months with rifampicin and isoniazid only, given 3 times per week. Given data that TB disease itself is associated with vitamin D depletion we will also recruit 80 otherwise healthy, adult family members of the pulmonary TB patients as a pilot substudy. Family members recruited will be those accompanying the TB patient to clinic.

Inclusion criteria

• Patient is age > 18 years;
• Patient has documented new case of smear-positive pulmonary TB;
• Patient has received ≤ 1 week of anti-TB therapy;
• The patient will receive anti-TB therapy in Tbilisi;
• Patient has provided informed consent.

Exclusion criteria

• Patient has had > 30 days of lifetime TB therapy;
• Patient is currently pregnant or lactating;
• Patient has a history of organ transplant;
• Patient has a history of cancer in past 5 years (ineligibility criteria does not include non-melanoma skin cancer);
• Patient has a history of seizures;
• Patient has a history of hypercalcemia;
• Patient has a history of hyperparathyroidism;
• Patient has a history of sarcoidosis;
• Patient has a history of nephrolithiasis (renal stones);
• Patient has taken oral corticosteroids in the past 30 days;
• Patient is currently using cytotoxic or immunosuppressive drugs;
• Patient currently has significant renal dysfunction (defined as a serum creatinine of >250mmol/L);
• Patient requires dialysis therapy;
• Patient has a history of cirrhosis;
• Patient is currently incarcerated;
• Patient is not able to complete all study visits in at the NCTBLD in Tbilisi.