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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Thomas R. Ziegler, MD, Emory University
ClinicalTrials.gov Identifier:
NCT00918086
First received: June 10, 2009
Last updated: July 10, 2014
Last verified: July 2014
  Purpose

Tuberculosis bacterium (TB) is a germ that can infect any part of the human body, especially the lungs. Vitamin D is a hormone present in humans that regulates blood electrolytes such as calcium and phosphate. There is new information that links vitamin D to the functioning of our immune system. The purpose of the study is to find out how vitamin D affects the immune system of patients with TB. We want to find out if correcting low vitamin D levels, in addition to getting standard therapy for TB, will help the immune system fight off TB infection more effectively.

The study will be done at the Georgia National Center for Tuberculosis and Lung Diseases (NCTBLD) in Tbilisi, Republic of Georgia. 220 patients with tuberculosis and 80 family members or household contacts of patients with tuberculosis will be participating in this study. TB patients, already receiving standard TB therapy, will be randomly assigned to either receive the Vitamin D pill or a placebo for a total of sixteen weeks. Neither the subject nor the investigator will know whether the subject has received the Vitamin D or the inactive placebo.The subject will orally consume the Vitamin D/placebo tablet 3 times a week for the 1st 8 weeks (while in hospital) and then once every other week for the last 8 weeks( during out-patient visits to the hospital).

The main study hypothesis is that Vitamin D supplementation helps patients with tuberculosis, who are on standard anti TB antibiotic therapy, get better faster.


Condition Intervention Phase
Tuberculosis
Dietary Supplement: Vitamin D pill
Dietary Supplement: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Supportive Care
Official Title: Impact of Vitamin D Supplementation on Host Immunity to Mycobacterium Tuberculosis and Response to Treatment: Building Translational Research Capacity in Nutrition and Infectious Diseases in the Republic of Georgia

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • The primary outcome for this intent-to-treat trial is the time to Mycobacterium tuberculosis sputum culture conversion to negative [ Time Frame: Up to 16 weeks from therapy start date ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Sputum culture result (positive or negative) [ Time Frame: 8 weeks after therapy start date ] [ Designated as safety issue: No ]

Enrollment: 199
Study Start Date: July 2009
Study Completion Date: July 2014
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vitamin D pill Dietary Supplement: Vitamin D pill
Oral tablet taken for 16 weeks
Placebo Comparator: Placebo Dietary Supplement: Placebo
An inactive pill that looks and tastes like the Vitamin D pill

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  1. Patient has had > 30 days of lifetime TB therapy;
  2. Patient is currently pregnant or lactating;
  3. Patient has a history of organ transplant;
  4. Patient has a history of cancer in past 5 years (ineligibility criteria does not include non-melanoma skin cancer);
  5. Patient has a history of seizures;
  6. Patient has a history of hypercalcemia;
  7. Patient has a history of hyperparathyroidism;
  8. Patient has a history of sarcoidosis;
  9. Patient has a history of nephrolithiasis (renal stones);
  10. Patient has taken oral corticosteroids in the past 30 days;
  11. Patient is currently using cytotoxic or immunosuppressive drugs;
  12. Patient currently has significant renal dysfunction (defined as a serum creatinine of >250mmol/L);
  13. Patient requires dialysis therapy;
  14. Patient has a history of cirrhosis;
  15. Patient is currently incarcerated;
  16. Patient is not able to complete all study visits in at the NCTBLD in Tbilisi.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00918086

Locations
Georgia
National Center for tuberculosis and Lung diseases
Tbilisi, Georgia, 0101
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Thomas R Ziegler, MD Emory University
  More Information

No publications provided

Responsible Party: Thomas R. Ziegler, MD, Professor of Medicine, Emory University
ClinicalTrials.gov Identifier: NCT00918086     History of Changes
Other Study ID Numbers: IRB00014641, Vitamin D Georgia Study
Study First Received: June 10, 2009
Last Updated: July 10, 2014
Health Authority: Georgia :Ethics committee for the National Center for Tuberculosis and Lung Diseases Of Georgia

Keywords provided by Emory University:
Vitamin D
Tuberculosis

Additional relevant MeSH terms:
Mycobacterium Infections
Tuberculosis
Actinomycetales Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Ergocalciferols
Vitamin D
Vitamins
Bone Density Conservation Agents
Growth Substances
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014