Replacement of Vitamin D in Patients With Active Tuberculosis (SUCCINCT)

This study has been completed.
Sponsor:
Collaborator:
Dow University of Health Sciences
Information provided by:
Aga Khan University
ClinicalTrials.gov Identifier:
NCT01130311
First received: May 25, 2010
Last updated: June 27, 2011
Last verified: June 2011
  Purpose

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.


Condition Intervention
Tuberculosis, Pulmonary
Drug: Cholecalciferol
Drug: Saline injection

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Supportive Care
Official Title: A Randomized, Placebo-Controlled, Double-Blinded, 250-Subject Clinical Trial of Vitamin D Replacement in Patients With Pulmonary Tuberculosis

Resource links provided by NLM:


Further study details as provided by Aga Khan University:

Primary Outcome Measures:
  • To measure difference in Clinical RESPONSES between test and control groups after treatment with vitamin D [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess the effects of vitamin D replacement on cytokine responses [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Stimulated and unstimulated IFN-gamma responses between the two groups will be compared


Enrollment: 259
Study Start Date: October 2009
Study Completion Date: December 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cholecalciferol (Vitamin D)
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
Intramuscular injection of 600,000 units of Cholecalciferol for 2 doses given at week 0 and week 4
Other Name: VITAMIN D
Placebo Comparator: SALINE, INTRAMUSCULAR INJECTION
NORMAL SALINE INJECTION WILL BE GIVEN TO THE CONTROL SUBJECTS at week 0 and week 4 of the trial
Drug: Saline injection
normal saline, intramuscular preperation,given in 2 doses at week 0 and week 4 of trial

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • 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.
  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: NCT01130311

Locations
Pakistan
Ojha Istitute of Chest Diseases
Karachi, Sind, Pakistan, 74800
Abbasi Shaheed Hospital
Karachi, Sind, Pakistan, 74812
Malir Chest Clinic
Karachi, Sind, Pakistan, 74831
Aga Khan University
Karachi, Sind, Pakistan, 74800
Sponsors and Collaborators
Aga Khan University
Dow University of Health Sciences
Investigators
Principal Investigator: Nawal Salahuddin, MBBS,FCCP Aga Khan University
  More Information

No publications provided by Aga Khan University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Nawal Salahuddin, Aga Khan University
ClinicalTrials.gov Identifier: NCT01130311     History of Changes
Other Study ID Numbers: AgaKhanU, 091014MED, 09014MED
Study First Received: May 25, 2010
Last Updated: June 27, 2011
Health Authority: Pakistan: Research Ethics Committee

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

ClinicalTrials.gov processed this record on September 18, 2014