Pulmonary Tuberculosis and Vitamin D

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2009 by Indian Council of Medical Research.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Department of Biotechnology-DBT India
Information provided by:
Indian Council of Medical Research
ClinicalTrials.gov Identifier:
NCT00507000
First received: July 23, 2007
Last updated: January 26, 2011
Last verified: July 2009

July 23, 2007
January 26, 2011
May 2008
September 2010   (final data collection date for primary outcome measure)
Time to convert from sputum positivity to negativity [ Time Frame: Two months after the last recruitment ] [ Designated as safety issue: Yes ]
Time to convert from sputum positivity to negativity [ Time Frame: Two months after the last recruitment ]
Complete list of historical versions of study NCT00507000 on ClinicalTrials.gov Archive Site
1 To study the relapse rate and safety assessment 2 To study the effect of Vitamin D supplementation on the pattern of effector immune function in patients suffering from pulmonary Tuberculosis. [ Time Frame: Three years ] [ Designated as safety issue: Yes ]
1 To study the relapse rate and safety assessment 2 To study the effect of Vitamin D supplementation on the pattern of effector immune function in patients suffering from pulmonary Tuberculosis. [ Time Frame: Three years ]
Not Provided
Not Provided
 
Pulmonary Tuberculosis and Vitamin D
Role of Oral Vitamin D as an Adjunct Therapy in Category I Pulmonary Tuberculosis Along With Assessment of Immunological Parameters. (Double-blind, Randomized, Placebo-Controlled, Clinical Trial)

Tuberculosis and vitamin D deficiency are important public health problems in India. Before the advent of effective antitubercular therapy, patients with tuberculosis were advised treatment and rest at sanatorium where sunshine was available in plenty. There have been reports associating vitamin D deficiency with tuberculosis in terms of incidence and beneficial response following addition of vitamin D to antitubercular therapy. Sputum AFB conversion rate is higher in patients with tuberculosis supplemented with vitamin D. The present study would systematically assess role of adjunct vitamin D therapy (cholecalciferol) in patients with pulmonary tuberculosis.

Tuberculosis and vitamin D deficiency are important public health problems in India. In recently published studies from our center, up to 90% of the apparently healthy subjects in Delhi were classified either as as vitamin D insufficient or deficient by using serum 25(OH)D cut off levels of 20 ng/ml and 32 ng/ml respectively. Before the advent of effective antitubercular therapy, patients with tuberculosis were advised treatment and rest at sanatorium where sunshine was available in plenty. In the western literature, there have been reports associating vitamin D deficiency with tuberculosis in terms of incidence and beneficial response following addition of vitamin D to antitubercular therapy. A few pilot studies have shown that sputum conversion rate is higher in patients with tuberculosis supplemented with vitamin D.

In the above context the mechanisms linking vitamin D deficiency and its effect on tuberculosis are currently under investigation. In order to understand the link two types of studies have been conducted (a) clinical studies associating vitamin D deficiency and tuberculosis and (b) in-vitro assessment of molecular immune changes related to vitamin D exposure. With the currently available knowledge, the linkage between the two disorders is being explained by the broad role of vitamin D deficiency in modulation of cell-mediated immunity.

Patients with military tuberculosis are characterized by decreased levels of Th1 cytokines and increased levels of IL-10 compared with the healthy infected and noninfected controls. Current literature suggests that long-term control of M. tuberculosis infection is associated with elevated Th1 responses and concomitant inhibition of the Th2 response

Peripheral blood mononuclear cells have been shown to express vitamin D receptors. Incubation of macro¬phages with physio¬logical concentration of 1,25 (OH)D [10-9M] results in inhibition of intracellular growth of Mycobacterium tuberculosis. 1,25-dihydroxycholecalciferol, has significant immunomodulatory effects leading to (a) shift in cytokine profile of T-helper (Th1 to Th2) and (b) reduced antigen presentation, reduced production of Th1-promoting cytokines, reduced expression of co-stimulatory molecules in the antigen-presenting cell. In addition, it was demonstrated that the addition of vitamin D3 derivatives inhibits the differentiation of IFN-gamma-producing Th1 cells while it augments the differentiation of IL-4- or IL-10-producing Th2 cells.

There are no systematic data from our country assessing association between vitamin D deficiency and tuberculosis and the possible role of vitamin D related modulation in the tuberculosis specific cellular immune response. The present study has been planned with the following hypothesis

Hypothesis: Patients with pulmonary tuberculosis and vitamin D deficiency when treated with vitamin and antitubercular therapy are likely to show early sputum conversion and immune response favoring resolution of tuberculosis

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Treatment
Tuberculosis
  • Drug: Cholecalciferol
    Drug: Cholecalciferol Drug: Cholecalciferol 60,000 IU sachet and calcium carbonate Oral cholecalciferol (vitamin D)60,000 IU weekly along with daily oral dose of 1 gm calcium carbonate for first two months followed by 1 gm of elemental calcium in form of calcium carbonate daily cholecalciferol (vitamin D)60,000 IU per month for the next four months Arms: A, Cholecalciferol
    Other Name: Vitamin D
  • Drug: Lactose granules
    Drug: Lactose placebo Lactose placebo granules in identical sachet given weekly and two lactose tablets for first two months followed one sachet of placebo granules every month and two tablets of lactose containing placebo tablets taken daily for next four months
    Other Name: lactose granules
  • Active Comparator: A, Cholecalciferol
    A Cholecalciferol Drug: Cholecalciferol 60,000 IU sachet and calcium carbonate Oral cholecalciferol (vitamin D)60,000 IU weekly along with daily oral dose of 1 gm calcium carbonate for first two months followed by 1 gm of elemental calcium in form of calcium carbonate daily cholecalciferol (vitamin D)60,000 IU per month for the next four months
    Intervention: Drug: Cholecalciferol
  • Placebo Comparator: Vitamin D and Tuberculosis
    B, Lactose
    Intervention: Drug: Lactose granules
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
150
September 2012
September 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. All patients of either sex with Newly diagnosed sputum positive pulmonary TB cases
  2. Aged between 18 to 60 yrs

Exclusion Criteria:

  1. Category II pulmonary TB and multi-drug resistant TB (MDR-TB) patients
  2. Presence of secondary immunodeficiency states : HIV, organ transplantation, diabetes mellitus, malignancy, treatment with corticosteroids
  3. Hepatitis B and C positivity
  4. Patients with extrapulmonary TB and/or patients requiring surgical intervention
  5. Currently receiving cytotoxic therapy, or have received it within the last 3 months
  6. Pregnancy and lactation
  7. Patients with a known seizure disorder
  8. Patients with known symptomatic cardiac disease, such as arrhythmias or coronary artery disease
  9. Patients with abnormal renal functions (serum creatinine more than 2 mg/dl; more than 2+ proteinuria)
  10. Patients with abnormal hepatic functions (bilirubin = 1.5 mg/dl; AST, ALT, SAP > 1.5 times above upper limit
  11. Patients with hematological abnormalities (WBC lesser than or equal to 3000/mm3; platelet count less than or equal to 100,000/mm3)
  12. Seriously ill and moribund patients with complications : tachypnoea, chronic cor pulmonale, congestive cardiac failure, BMI<15, severe hypoalbuminemia
  13. Patients unable to comply with the treatment regimen
  14. Patients with history of alcohol or drug abuse
Both
18 Years to 60 Years
No
Contact information is only displayed when the study is recruiting subjects
India
 
NCT00507000
BT/pr7898/Med/14/1179/2006
Yes
Depratment of Biotechnology (Dr R Goswami, Principal Investigator), All India Institute of Medical sciences, New delhi
Indian Council of Medical Research
Department of Biotechnology-DBT India
Principal Investigator: Ravinder Goswami, MD, DM Associate Professor, Depratment of Endocrinology and Metabolism, All India Institute of Medical Sciences, New delhi 110029
Principal Investigator: SK Sharma, MD, PHD Head, Depratment of Medicine, All India Institute of Medical Sciences, New Delhi 110029
Principal Investigator: DK Mitra, MBBS, PhD Associate professor, Department of Transplant immunology and immunogenetics, All India Institute of Medicasl Sciences, New delhi 110029, India
Principal Investigator: Urvashi B Singh, MD, PhD Assistant Professor, Deprtament of Microbiology, All India Institute of Medical Sciences, new delhi 110029
Principal Investigator: Nandita Gupta, PhD Additional Porfessor, Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi 110029, India
Study Director: Bindu Dey, PhD. Adviser, Department of Biotechnology, Lodhi Road, New Delhi-110003, India
Indian Council of Medical Research
July 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP