Pulmonary Tuberculosis and Vitamin D

Tuberculosis Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00507000
• Other study ID #: BT/pr7898/Med/14/1179/2006
• Status: Active, not recruiting
• Phase: Phase 3
• First received: July 23, 2007
• Last updated: January 26, 2011
• Start date: May 2008
• Est. completion date: September 2012

Study information

• Verified date: July 2009
• Source: Indian Council of Medical Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: India: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 150
• Est. completion date: September 2012
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Tuberculosis
• Tuberculosis, Pulmonary

Intervention

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
• 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

Locations

Country	Name	City	State
India	Depratment of Endocrinology;Medicine, All India Institute of Medical sciences, and DBT	Delhi	New Delhi

Sponsors (2)

Lead Sponsor	Collaborator
Indian Council of Medical Research	Ministry of Science and Technology, India

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to convert from sputum positivity to negativity		Two months after the last recruitment	Yes
Secondary	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.		Three years	Yes