Immune Reconstitution in Tuberculosis Disease

Pulmonary Tuberculosis (TB) Clinical Trial

— IRETB  

Official title:

Immune Reconstitution in Tuberculosis Disease Using Antimicrobial Treatment With Vitamin D and Phenylbutyrate

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01698476
• Other study ID #: IRETB-2012
• Status: Completed
• Phase: Phase 2
• First received: September 25, 2012
• Last updated: February 4, 2016
• Start date: September 2012
• Est. completion date: August 2015

Study information

• Verified date: February 2016
• Source: Karolinska Institutet
• Contact: n/a
• Is FDA regulated: No
• Health authority: Ethiopia: Food, Medicine and Health Care Administration and Control Authority of Ethiopia (FMHACA)
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 390
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 > 3 mmol/L) identified at baseline.

Pregnant and breast feeding women.

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pulmonary Tuberculosis (TB)
• Tuberculosis
• Tuberculosis, Pulmonary

Intervention

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 tablets

Locations

Country	Name	City	State
Ethiopia	Black Lion Hospital (BLH), Addis Ababa University, Faculty of Medicine	Addis Ababa	Lideta sub city

Sponsors (3)

Lead Sponsor	Collaborator
Karolinska Institutet	Addis Ababa University, Armauer Hansen Research Institute, Ethiopia

Country where clinical trial is conducted

Ethiopia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite clinical TB score	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, 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).	0 (baseline) compared to 8 weeks.	Yes
Secondary	Clinical secondary endpoints	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).	0-4, 8, 16 and 24 weeks	Yes
Secondary	Laboratory secondary endpoints	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).	0, 4, 8, 16, 24 weeks	No