TuberculosisPhase 3NCT00507000
Pulmonary Tuberculosis and Vitamin D
A Phase 3 study testing Cholecalciferol and Lactose granules in people with Tuberculosis, run by Indian Council of Medical Research at 1 site in India.
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Tuberculosis
- What is being tested?
- Cholecalciferol and Lactose granules
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 1 siteIndia
- Study dates
- May 2008to Sep 2012
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- All patients of either sex with Newly diagnosed sputum positive pulmonary TB cases
- Aged between 18 to 60 yrs
Who cannot join
- Category II pulmonary TB and multi-drug resistant TB (MDR-TB) patients
- Presence of secondary immunodeficiency states : HIV, organ transplantation, diabetes mellitus, malignancy, treatment with corticosteroids
- Hepatitis B and C positivity
- Patients with extrapulmonary TB and/or patients requiring surgical intervention
- Currently receiving cytotoxic therapy, or have received it within the last 3 months
- Pregnancy and lactation
Show all 14Show fewer
- Patients with a known seizure disorder
- Patients with known symptomatic cardiac disease, such as arrhythmias or coronary artery disease
- Patients with abnormal renal functions (serum creatinine more than 2 mg/dl; more than 2+ proteinuria)
- Patients with abnormal hepatic functions (bilirubin = 1.5 mg/dl; AST, ALT, SAP > 1.5 times above upper limit
- Patients with hematological abnormalities (WBC lesser than or equal to 3000/mm3; platelet count less than or equal to 100,000/mm3)
- Seriously ill and moribund patients with complications : tachypnoea, chronic cor pulmonale, congestive cardiac failure, BMI<15, severe hypoalbuminemia
- Patients unable to comply with the treatment regimen
- Patients with history of alcohol or drug abuse
Trial locations and contacts
1 site in 1 country.
India1 site
Depratment of Endocrinology;Medicine, All India Institute of Medical sciences, and DBT
Delhi, New Delhi, 110029
About this study
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)
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.
Read the 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
- Conditions
- Tuberculosis
- Being tested
- Cholecalciferol, Lactose granules
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CholecalciferolDrug
Also called Vitamin D
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 granulesDrug
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
| Study group | Role | What they receive |
|---|---|---|
| A, Cholecalciferol | Active comparator | 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 Receives: Drug: Cholecalciferol |
| Vitamin D and Tuberculosis | Placebo comparator | B, Lactose Receives: Drug: Lactose granules |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to convert from sputum positivity to negativity
Measured: Two months after the last recruitment
Secondary outcomes (1)
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.
Measured: Three years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2007 (estimated)
- Study startMay 2008
- Primary completionSep 2010 (estimated)
- Study completionSep 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Indian Council of Medical Research
- Sponsor type
- Other government
- Collaborators
- Ministry of Science and Technology, India
- Investigators
- Ravinder Goswami, MD, DM, Principal investigator, Associate Professor, Depratment of Endocrinology and Metabolism, All India Institute of Medical Sciences, New delhi 110029SK Sharma, MD, PHD, Principal investigator, Head, Depratment of Medicine, All India Institute of Medical Sciences, New Delhi 110029DK Mitra, MBBS, PhD, Principal investigator, Associate professor, Department of Transplant immunology and immunogenetics, All India Institute of Medicasl Sciences, New delhi 110029, IndiaUrvashi B Singh, MD, PhD, Principal investigator, Assistant Professor, Deprtament of Microbiology, All India Institute of Medical Sciences, new delhi 110029Nandita Gupta, PhD, Principal investigator, Additional Porfessor, Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi 110029, IndiaBindu Dey, PhD., Study director, Adviser, Department of Biotechnology, Lodhi Road, New Delhi-110003, India
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00507000
- Sponsor's protocol ID
- BT/pr7898/Med/14/1179/2006
- Status last verified
- Jul 2009
- First submitted
- 23 Jul 2007
- Last updated
- 27 Jan 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00507000
- Acronym / sponsor ID
- BT/pr7898/Med/14/1179/2006
- Conditions
- Tuberculosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Indian Council of Medical ResearchOther government
- Collaborators
- Ministry of Science and Technology, India
- Study start
- May 2008
- Primary completion
- Sep 2010 (estimated)
- Study completion
- Sep 2012 (estimated)
- First posted
- 25 Jul 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A, Cholecalciferol | Active comparator | Drug: CholecalciferolA 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 |
| Vitamin D and Tuberculosis | Placebo comparator | Drug: Lactose granulesB, Lactose |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- All patients of either sex with Newly diagnosed sputum positive pulmonary TB cases
- Aged between 18 to 60 yrs
Key exclusion criteria (14 listed)
- Category II pulmonary TB and multi-drug resistant TB (MDR-TB) patients
- Presence of secondary immunodeficiency states : HIV, organ transplantation, diabetes mellitus, malignancy, treatment with corticosteroids
- Hepatitis B and C positivity
- Patients with extrapulmonary TB and/or patients requiring surgical intervention
- Currently receiving cytotoxic therapy, or have received it within the last 3 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CholecalciferolAlso: Vitamin DDrug: 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 | Drug | A, Cholecalciferol |
| Lactose granulesDrug: 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 | Drug | Vitamin D and Tuberculosis |
Primary outcome
Time to convert from sputum positivity to negativity
Time frame: Two months after the last recruitment
1 secondary outcome
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2011.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ravinder Goswami, MD, DM principal investigator
Associate Professor, Depratment of Endocrinology and Metabolism, All India Institute of Medical Sciences, New delhi 110029
SK Sharma, MD, PHD principal investigator
Head, Depratment of Medicine, All India Institute of Medical Sciences, New Delhi 110029
DK Mitra, MBBS, PhD principal investigator
Associate professor, Department of Transplant immunology and immunogenetics, All India Institute of Medicasl Sciences, New delhi 110029, India
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cholecalciferol and Lactose granules in people with Tuberculosis, run by Indian Council of Medical Research at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Jan 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to convert from sputum positivity to negativity (time frame: Two months after the last recruitment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2011.