TY - JOUR
T1 - Vitamin D accelerates clinical recovery from tuberculosis
T2 - Results of the SUCCINCT Study [Supplementary Cholecalciferol in recovery from tuberculosis]. A randomized, placebo-controlled, clinical trial of vitamin D supplementation in patients with pulmonary tuberculosis'
AU - Salahuddin, Nawal
AU - Ali, Farheen
AU - Hasan, Zahra
AU - Rao, Nisar
AU - Aqeel, Masooma
AU - Mahmood, Faisal
N1 - Funding Information:
The study was funded by a grant from the Aga Khan University Research Council. The authors report that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
Funding Information:
This was a randomized double blinded, multi-centre, placebo-controlled clinical trial. The study was approved by the institutional review boards of the participating centres; Aga Khan University Hospital (ERC approval no. 1238-Med/ERC-09) and Ojha Institute of Chest Diseases, Dow University Hospital (IRB-94/DUHS-09) and is listed on clinicaltrials.gov (NCT01130311). The trial was funded through a grant obtained from the Aga Khan University Research Council (URC grant No. 0000058579). The study was conducted from October 2009 to July 2010 with enrolment of the first participant in October 2009 and last participant in April 2010. The protocol was made available at clinicaltrials.gov in May 2010. All patients provided written, informed consent prior to participation. Consecutive adult patients (≥16 years) with smear positive, active pulmonary TB diagnosed within one week and enrolled at outpatient TB clinics were included. Based on clinical history taking and clinical records, patients with extrapulmonary TB, human immunodeficiency virus (HIV) infection, hepatic disease, renal failure, malignancy, diabetes mellitus, pregnancy, sarcoidosis, hyperparathyroidism or those taking any corticosteroids, immunosuppressive agents, thiazide diuretics or drugs known to interfere with vitamin D levels (phenytoin, phenobarbital, carbamazepine, theophylline) were excluded from the study.
PY - 2013/1/19
Y1 - 2013/1/19
N2 - Background: Vitamin D enhances host protective immune responses to Mycobacterium tuberculosis by suppressing Interferon-gamma (IFN-g) and reducing disease associated inflammation in the host. The objectives of this study were to determine whether vitamin D supplementation to patients with tuberculosis (TB) could influence recovery.Methods: Two hundred and fifty nine patients with pulmonary TB were randomized to receive either 600,000 IU of Intramuscular vitamin D3 or placebo for 2 doses. Assessments were performed at 4, 8 and 12 weeks. Early secreted and T cell activated 6 kDa (ESAT6) and Mycobacterium tuberculosis sonicate (MTBs) antigen induced whole blood stimulated IFN-g responses were measured at 0 and 12 weeks. Statistical comparisons between outcome variables at 0 and 12 weeks were performed using Student's t-test and Chi2 tests.Results: After 12 weeks, the vitamin D supplemented arm demonstrated significantly greater mean weight gain (kg) + 3.75, (3.16 - 4.34) versus + 2.61 (95% CI 1.99 - 3.23) p 0.009 and lesser residual disease by chest radiograph; number of zones involved 1.35 v/s 1.82 p 0.004 (95% CI 0.15, 0.79) and 50% or greater reduction in cavity size 106 (89.8%) v/s 111 (94.8%), p 0.035. Vitamin D supplementation led to significant increase in MTBs-induced IFN-g secretion in patients with baseline 'Deficient' 25-hydroxyvitamin D serum levels (p 0.021).Conclusions: Supplementation with high doses of vitamin D accelerated clinical, radiographic improvement in all TB patients and increased host immune activation in patients with baseline 'Deficient' serum vitamin D levels. These results suggest a therapeutic role for vitamin D in the treatment of TB.Trial registration: ClinicalTrials.gov; No. NCT01130311; URL: clinicaltrials.gov.
AB - Background: Vitamin D enhances host protective immune responses to Mycobacterium tuberculosis by suppressing Interferon-gamma (IFN-g) and reducing disease associated inflammation in the host. The objectives of this study were to determine whether vitamin D supplementation to patients with tuberculosis (TB) could influence recovery.Methods: Two hundred and fifty nine patients with pulmonary TB were randomized to receive either 600,000 IU of Intramuscular vitamin D3 or placebo for 2 doses. Assessments were performed at 4, 8 and 12 weeks. Early secreted and T cell activated 6 kDa (ESAT6) and Mycobacterium tuberculosis sonicate (MTBs) antigen induced whole blood stimulated IFN-g responses were measured at 0 and 12 weeks. Statistical comparisons between outcome variables at 0 and 12 weeks were performed using Student's t-test and Chi2 tests.Results: After 12 weeks, the vitamin D supplemented arm demonstrated significantly greater mean weight gain (kg) + 3.75, (3.16 - 4.34) versus + 2.61 (95% CI 1.99 - 3.23) p 0.009 and lesser residual disease by chest radiograph; number of zones involved 1.35 v/s 1.82 p 0.004 (95% CI 0.15, 0.79) and 50% or greater reduction in cavity size 106 (89.8%) v/s 111 (94.8%), p 0.035. Vitamin D supplementation led to significant increase in MTBs-induced IFN-g secretion in patients with baseline 'Deficient' 25-hydroxyvitamin D serum levels (p 0.021).Conclusions: Supplementation with high doses of vitamin D accelerated clinical, radiographic improvement in all TB patients and increased host immune activation in patients with baseline 'Deficient' serum vitamin D levels. These results suggest a therapeutic role for vitamin D in the treatment of TB.Trial registration: ClinicalTrials.gov; No. NCT01130311; URL: clinicaltrials.gov.
UR - http://www.scopus.com/inward/record.url?scp=84872332054&partnerID=8YFLogxK
U2 - 10.1186/1471-2334-13-22
DO - 10.1186/1471-2334-13-22
M3 - Article
C2 - 23331510
AN - SCOPUS:84872332054
SN - 1471-2334
VL - 13
JO - BMC Infectious Diseases
JF - BMC Infectious Diseases
IS - 1
M1 - 22
ER -
