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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
  Purpose

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.


Condition Intervention Phase
Tuberculosis
Drug: Cholecalciferol
Drug: Lactose granules
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Indian Council of Medical Research:

Primary Outcome Measures:
  • Time to convert from sputum positivity to negativity [ Time Frame: Two months after the last recruitment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 150
Study Start Date: May 2008
Estimated Study Completion Date: September 2012
Estimated Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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
Placebo Comparator: Vitamin D and Tuberculosis
B, Lactose
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

Detailed 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

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00507000

Locations
India
Depratment of Endocrinology;Medicine, All India Institute of Medical sciences, and DBT
Delhi, New Delhi, India, 110029
Sponsors and Collaborators
Indian Council of Medical Research
Department of Biotechnology-DBT India
Investigators
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
  More Information

No publications provided

Responsible Party: Depratment of Biotechnology (Dr R Goswami, Principal Investigator), All India Institute of Medical sciences, New delhi
ClinicalTrials.gov Identifier: NCT00507000     History of Changes
Other Study ID Numbers: BT/pr7898/Med/14/1179/2006
Study First Received: July 23, 2007
Last Updated: January 26, 2011
Health Authority: India: Institutional Review Board

Additional relevant MeSH terms:
Tuberculosis
Tuberculosis, Pulmonary
Actinomycetales Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Lung Diseases
Mycobacterium Infections
Respiratory Tract Diseases
Respiratory Tract Infections
Calcium Carbonate
Cholecalciferol
Ergocalciferols
Vitamin D
Vitamins
Antacids
Bone Density Conservation Agents
Growth Substances
Micronutrients
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 23, 2014