Immune Reconstitution in Tuberculosis Disease (IRETB)
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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 |
- 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).
- 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).
- 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 |
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| Contact: Endale Kassa, MD | 251-911228562 | endalekassalulu@gmail.com |
| Contact: Wondwossen Amogne, MD | 251-911406179 | wonamogne@yahoo.com |
| 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 | |
| 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:
|
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 4-phenylbutyric acid Therapeutic Uses Pharmacologic Actions Micronutrients Growth Substances Physiological Effects of Drugs Bone Density Conservation Agents Antineoplastic Agents |
ClinicalTrials.gov processed this record on May 23, 2013