Replacement of Vitamin D in Patients With Active Tuberculosis

NCT01130311 | Completed

• 3 other identifiers: AgaKhanU091014MED09014MED
• Study Type: interventional
• Target: 259
• Locations: 1 country
• Sites: 4

Brief Summary

Tuberculosis is a global public health problem. One third of the world's population is infected with tuberculosis (TB) with almost 2 million deaths per year globally. According to the WHO, Pakistan ranks 8th amongst the 22 high TB burden countries, with an estimated prevalence is 263 cases /100,000 populations. In spite of effective therapy for drug sensitive TB, treatment failure occurs frequently leading to concerns for the emergence of multi-drug resistant (MDR) and extensively drug resistant (XDR) mycobacterial strains. Therefore in the recent years, interest has been generated regarding the role of adjuvant immunomodulating therapy for the treatment of TB. WHO has classified tuberculosis by disease severity into 3 distinct categories; mild, moderate and severe according to clinical presentations and host factors. Severity of disease has been linked to mycobacterium genotypes and with host factors such as vitamin D deficiency Vitamin D is a hormone produced by the body in response to sun exposure. Independent of it's effects on bone mineralization, vitamin D is recognized to have numerous immune modulating effects; some specific to mycobacterium tuberculosis. Therefore vitamin D may enhance the host immune responses against the pathogen. Vitamin D status can be accurately determined by measuring the serum levels of 25-(OH) D3. A recent systemic review and meta-analysis explored the association between low serum vitamin D and risk of active tuberculosis and concluded that patients with tuberculosis have lower serum levels of vitamin D than healthy controls when matched for sex, age, ethnicity, diet and geographical location. Vitamin D deficiency is not a life threatening condition. It usually is unrecognized or can present with generalized 'aches and pains' due to osteomalacia. The recommended dose for treatment of vitamin D deficiency is 200,000 IU/ month or 50,000 IU/ week, both given for 2 months or until the serum vitamin D level is \> 30 ng/ml. Bone mineral density changes are usually completed by 10 weeks of treatment. The investigators hypothesize that by replacing vitamin D in patients with active pulmonary tuberculosis, the 'Time to Recovery' can be shortened.Our aims are to determine whether replacing patients with insufficient and deficient levels of vitamin D affects the clinical outcome of the disease.

Conditions

Tuberculosis, Pulmonary

Outcome Measures

Primary Outcomes (1)

• To measure difference in Clinical RESPONSES between test and control groups after treatment with vitamin D

  12 weeks

Secondary Outcomes (1)

• To assess the effects of vitamin D replacement on cytokine responses

  12 weeks

Study Arms (2)

Cholecalciferol (Vitamin D)

EXPERIMENTAL

Intramuscular injection of VITAMIN D, 600,000 UNITS WILL BE GIVEN TO THE TEST SUBJECTS AT WEEK 0 and at week 4 OF the TRIAL

Drug: Cholecalciferol

SALINE, INTRAMUSCULAR INJECTION

PLACEBO COMPARATOR

NORMAL SALINE INJECTION WILL BE GIVEN TO THE CONTROL SUBJECTS at week 0 and week 4 of the trial

Drug: Saline injection

Interventions

Cholecalciferol DRUG

Intramuscular injection of 600,000 units of Cholecalciferol for 2 doses given at week 0 and week 4

Also known as: VITAMIN D

Cholecalciferol (Vitamin D)

Saline injection DRUG

normal saline, intramuscular preperation,given in 2 doses at week 0 and week 4 of trial

SALINE, INTRAMUSCULAR INJECTION

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults (≥16 years on 1st March 2009) Males and Nonpregnant females
• Active Pulmonary Tuberculosis diagnosed by Sputum Smear positivity for Acid fast bacilli (AFB)
• Not already on antituberculous treatment
• Not receiving vitamin D replacement or supplementation

You may not qualify if:

• History of having been treated with antimycobacterial therapy for \< 6 months or with \< 4 first-line anti-tuberculous drugs
• Extra- pulmonary TB
• Immune suppressed; with HIV infection, hepatic, renal failure, malignancy, diabetes mellitus
• Sarcoidosis, hyperparathyroidism
• Already on or requiring corticosteroids, immunosuppressive agents, thiazide diuretics
• Breast feeding or pregnant
• Symptomatic cardiac disease
• Seriously ill or moribund patients with advanced respiratory impairment (cor pulmonale, hypercapnia, respiratory acidosis, congestive cardiac failure)
• Allergy/sensitivity to study drugs or their formulations.
• Concomitant use of drugs known to interfere with vitamin D levels; phenytoin, phenobarbital, carbamazepine, theophylline
• Inability or unwillingness of subject or legal guardian/representative to give written informed consent.

Sponsors & Collaborators

• Aga Khan University: lead
• Dow University of Health Sciences: collaborator

Study Sites (4)

Aga Khan University

Karachi, Sindh, 74800, Pakistan

Location

Ojha Istitute of Chest Diseases

Karachi, Sindh, 74800, Pakistan

Location

Abbasi Shaheed Hospital

Karachi, Sindh, 74812, Pakistan

Location

Malir Chest Clinic

Karachi, Sindh, 74831, Pakistan

Location

Related Publications (2)

• Hasan Z, Salahuddin N, Rao N, Aqeel M, Mahmood F, Ali F, Ashraf M, Rahman F, Mahmood S, Islam M, Dildar B, Anwer T, Oiighor F, Sharif N, Ullah AR. Change in serum CXCL10 levels during anti-tuberculosis treatment depends on vitamin D status [Short Communication]. Int J Tuberc Lung Dis. 2014 Apr;18(4):466-9. doi: 10.5588/ijtld.13.0460.

  PMID: 24670704 DERIVED

• Salahuddin N, Ali F, Hasan Z, Rao N, Aqeel M, Mahmood F. Vitamin D accelerates clinical recovery from tuberculosis: 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'. BMC Infect Dis. 2013 Jan 19;13:22. doi: 10.1186/1471-2334-13-22.

  PMID: 23331510 DERIVED

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

Cholecalciferol; Vitamin D; Sodium Chloride

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Secosteroids; Membrane Lipids; Lipids; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Nawal Salahuddin, MBBS,FCCP

  Aga Khan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 25, 2010
• First Posted: May 26, 2010
• Study Start: October 1, 2009
• Primary Completion: April 1, 2010
• Study Completion: December 1, 2010
• Last Updated: June 28, 2011

Record last verified: 2011-06

Locations

PA (4)