Immune Reconstitution in Tuberculosis Disease

NCT01698476 | Completed Phase 2 DMC

• 1 other identifier: IRETB-2012
• Study Type: interventional
• Target: 390
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pulmonary Tuberculosis (TB)

Keywords

pulmonary TB; cholecalciferol; sodium phenylbutyrate; antimicrobial peptides; immune response

Outcome Measures

Primary Outcomes (1)

• 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.

Secondary Outcomes (2)

• Clinical secondary endpoints

  0-4, 8, 16 and 24 weeks

• Laboratory secondary endpoints

  0, 4, 8, 16, 24 weeks

Study Arms (2)

vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)

ACTIVE COMPARATOR

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)

Placebo tablets

PLACEBO COMPARATOR

Placebo tablets for vitamin D once daily and placebo tablets for PBA (phenylbutyrate) twice daily for 16 weeks.

Drug: Placebo tablets

Interventions

vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate) DRUG

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.

vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)

Placebo tablets DRUG

Placebo tablets

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Karolinska Institutet: lead
• Addis Ababa University: collaborator
• Armauer Hansen Research Institute, Ethiopia: collaborator

Study Sites (1)

Black Lion Hospital (BLH), Addis Ababa University, Faculty of Medicine

Addis Ababa, Lideta Sub City, Ethiopia

Location

Related Publications (1)

• Bekele A, Gebreselassie N, Ashenafi S, Kassa E, Aseffa G, Amogne W, Getachew M, Aseffa A, Worku A, Raqib R, Agerberth B, Hammar U, Bergman P, Aderaye G, Andersson J, Brighenti S. Daily adjunctive therapy with vitamin D3 and phenylbutyrate supports clinical recovery from pulmonary tuberculosis: a randomized controlled trial in Ethiopia. J Intern Med. 2018 Sep;284(3):292-306. doi: 10.1111/joim.12767. Epub 2018 May 23.

  PMID: 29696707 DERIVED

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

Vitamin D; Cholecalciferol; 4-phenylbutyric acid

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)

Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholestenes; Cholestanes; Sterols; Membrane Lipids; Lipids

Study Officials

• Susanna Brighenti, PhD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: September 25, 2012
• First Posted: October 3, 2012
• Study Start: September 1, 2012
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: February 5, 2016

Record last verified: 2016-02

Locations

ET (1)