Immune Reconstitution in Tuberculosis Disease (IRETB)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by Karolinska Institutet
Sponsor:
Collaborators:
Addis Ababa University
Armauer Hansen Research Institute (AHRI), Addis Ababa, Ethiopia
Information provided by (Responsible Party):
Susanna Brighenti, Karolinska Institutet
ClinicalTrials.gov Identifier:
NCT01698476
First received: September 25, 2012
Last updated: October 2, 2012
Last verified: October 2012
  Purpose

The aim with study is to provide adjunctive therapy with vitamin D and phenylbutyrate together with standard anti-tuberculosis treatment to significantly improve clinical recovery among patients with untreated, active pulmonary tuberculosis.


Condition Intervention Phase
Pulmonary Tuberculosis (TB)
Drug: vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)
Drug: Placebo tablets
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Immune Reconstitution in Tuberculosis Disease Using Antimicrobial Treatment With Vitamin D and Phenylbutyrate

Resource links provided by NLM:


Further study details as provided by Karolinska Institutet:

Primary Outcome Measures:
  • Composite clinical TB score [ Time Frame: 0 (baseline) compared to 8 weeks. ] [ Designated as safety issue: Yes ]
    A previously described composite clinical TB score will be used to monitor the efficacy of vitamin D and phenylbutyrate treatment among TB patients on standard chemotherapy. The numerical TB score will include self-reported clinical symptoms (cough, night sweats and chest pain) as well as different parameters determined upon clinical examination anemia/conjunctival pallor, haemoptysis, dyspnoea, tachycardia, positive finding at lung auscultation, fever, low body mass index (BMI) and low mid upper arm circumference (MUAC). The TB score will be determined at the time of diagnosis (time point 0) and at 4, 8, 16 and 24 weeks after initiation of antimicrobial treatment with vitamin D and phenylbutyrate. The primary endpoint will be assessed at time point 8 weeks compared to baseline (time point 0).


Secondary Outcome Measures:
  • Clinical secondary endpoints [ Time Frame: 0-4, 8, 16 and 24 weeks ] [ Designated as safety issue: Yes ]

    Clinical composite TB score (0, 4, 16, 24 weeks).

    Modified clinical composite TB score (0, 4, 8, 16, 24 weeks).

    Chest X-ray (0, 4, 8, 16, 24 weeks).

    Time to sputum- and/or TB culture conversion (0, 1, 2, 3, 4, 8 weeks).


  • Laboratory secondary endpoints [ Time Frame: 0, 4, 8, 16, 24 weeks ] [ Designated as safety issue: No ]

    Peripheral CD4/CD8 T cell counts.

    Antibodies in lymphocytes secertions (ALS) (S Ashenafi, Thorax, 2012).

    Quantiferon-in-tube TB-gold (QFT).

    Plasma levels of vitamin D, LL-37 and also cytokine/chemokine profiles.

    Functional studies of immune cells (PBMCs).



Other Outcome Measures:
  • Interim analysis [ Designated as safety issue: Yes ]
    An interim analysis will be performed after approx. 100-150 patients have been included into the study.


Estimated Enrollment: 300
Study Start Date: September 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)
Dose of interventions: 5,000 IU of vitamin D (cholecalciferol tablets) once daily and 500 mg PBA (sodium phenylbutyrate tablets) twice daily for 16 weeks.
Drug: vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)
Dose of interventions: 5,000 IU of vitamin D (cholecalciferol tablets) once daily and 500 mg PBA (sodium phenylbutyrate tablets) twice daily for 16 weeks.
Placebo Comparator: Placebo tablets
Placebo tablets for vitamin D once daily and placebo tablets for PBA (phenylbutyrate) twice daily for 16 weeks.
Drug: Placebo tablets

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

HIV negative patients, adult patients >18 years who has not started anti-TB therapy.

Newly diagnosed pulmonary TB confirmed by microscopy or culture but also sputum-negative clinical TB cases (defined according to the WHO 2006 criteria for sputum smear-negative TB ie. clinical symptoms of TB, chest X-ray findings and response to standard treatment).

Exclusion Criteria:

Patients who have already started treatment with anti-TB drugs for more that 5 days.

HIV-positive patients.

History of anti-TB treatment in the past 2 years.

Local extra-pulmonary TB in the absence of lung manifestations.

Hypercalcaemia (serum calcium > 2.6 mmol/L) identified at baseline.

Pregnant and breast feeding women.

Any known liver or kidney function abnormality, malignancy or patients treated with cardiac glycosides.

  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: NCT01698476

Contacts
Contact: Endale Kassa, MD 251-911228562 endalekassalulu@gmail.com
Contact: Wondwossen Amogne, MD 251-911406179 wonamogne@yahoo.com

Locations
Ethiopia
Black Lion Hospital (BLH), Addis Ababa University, Faculty of Medicine Recruiting
Addis Ababa, Lideta sub city, Ethiopia
Contact: Endale Kassa, MD    251-911228562    endalekassalulu@gmail.com   
Principal Investigator: Endale Kassa, MD         
Sponsors and Collaborators
Karolinska Institutet
Addis Ababa University
Armauer Hansen Research Institute (AHRI), Addis Ababa, Ethiopia
Investigators
Principal Investigator: Susanna Brighenti, PhD Karolinska Institutet
  More Information

No publications provided

Responsible Party: Susanna Brighenti, Assistant professor, Karolinska Institutet
ClinicalTrials.gov Identifier: NCT01698476     History of Changes
Other Study ID Numbers: IRETB-2012
Study First Received: September 25, 2012
Last Updated: October 2, 2012
Health Authority: Ethiopia: Food, Medicine and Health Care Administration and Control Authority of Ethiopia (FMHACA)

Keywords provided by Karolinska Institutet:
pulmonary TB
cholecalciferol
sodium phenylbutyrate
antimicrobial peptides
immune response

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

ClinicalTrials.gov processed this record on August 01, 2014