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NCT Number: NCT01580007

Clinical Trial of Phenylbutyrate and Vitamin D in Tuberculosis (TB)

Vitamin D exerts its effects via the Vitamin D Receptor (VDR) present in activated macrophages and induces expression and release of the cathelicidin, LL-37, a human antimicrobial peptide involved in killing of MTB. We aimed to investigate whether treatment of newly diagnosed pulmonary TB patients for 2 months with adjunctive PBA and vitamin D (Cholecalciferol) in combination with standard DOTS therapy (i) can improve response to standard short course TB therapy towards a rapid recovery; (ii) can induce expression of LL-37 in macrophages; (iii) can enhance killing capacity of macrophages isolated from TB patients infected in vitro with MTB; and (iv) does not evoke any adverse effects.

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Key information

Conditions

Pulmonary Tuberculosis Actinomycetales Infections Bacterial Infections Bacterial Infections and Mycoses Gram-Positive Bacterial Infections Infections Lung Diseases Mycobacterium Infections Respiratory Tract Diseases Respiratory Tract Infections Tuberculosis Tuberculosis, Pulmonary

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

National Institute of Diseases of Chest and Hospital (NIDCH)

Dhaka, 1212, Bangladesh

About this study

This is a double-blind, randomized, placebo controlled clinical trial on clinical efficacy of phenylbutyrate and vitamin D3 therapy daily for 2 months in newly diagnosed sputum smear positive pulmonary TB patients. The clinical trial will take place in the National Institute of the Diseases of the Chest and Hospital (NIDCH) in Dhaka, Bangladesh.

Our specific aims are:

Objective 1: To determine the optimal oral dose of PBA required for induction of antimicrobial peptide in macrophages from healthy adults.

Objective 2

The second aim of this study is to determine whether adjunctive sodium phenylbutyrate and vitamin D treatment (for 2 months) of newly diagnosed pulmonary TB patients:

  • Can improve response to standard short course TB therapy towards a rapid recovery (clinical, radiological, mycobacterial).
  • Can induce expression of LL-37 in macrophages (immunological).
  • Can enhance killing capacity of macrophages from TB patients infected in vitro with MTB (functional measures of treatment outcome).

Study Design: The study will be a randomized, double blind (Subject, Caregiver, Investigator, Outcomes Assessor), placebo control trial for 2 months. It will also be a safety and efficacy phase III study. The study will have a 4x4 factorial design with 4-cell interventions. Enrolled patients will be randomized into the following four treatment arms in a 1:1:1:1 ratio:

Group 1: PBA Group 2: Vitamin D3 (Cholecalciferol) Group 3: PBA plus vitamin D3 Group 4: Placebo

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adults, 18-60 years with sputum smear positive pulmonary TB
  • New cases only
  • Gender, both
  • Consent to enroll in the study

Exclusion criteria

  • Hypercalcaemia (serum calcium > 2.6 mmol/L) identified at baseline
  • Taking vitamin D
  • Pregnant and lactating
  • Any known liver or kidney function abnormality, malignancy

Treatment and study plan

Active Sodium Phenylbutyrate and active cholecalciferol

Drug

Sodium Phenylbutyrate: 500 mg twice daily orally for 2 months Cholecalciferol: 5000 IU once daily orally for 2 months

Other names: triButyrate®, Vigantol oil

Placebo Sodium Phenylbutyrate plus active cholecalciferol

Drug

Placebo Sodium Phenylbutyrate: twice daily orally for 2 months Cholecalciferol: 5000 IU once daily for 2 months

Other names: Vigantol oil, Placebo Phenylbutyrate

Active Sodium Phenylbutyrate and placebo cholecalciferol

Drug

Sodium phenylbutyrate: 500 mg twice daily orally for 2 months Placebo cholecalciferol: once daily orally for 2 months

Other names: triButyrate®, Placebo vigantol oil

Placebo Sodium Phenylbutyrate plus placebo cholecalciferol

Drug

Placebo Sodium Phenylbutyrate: twice daily orally for 2 months Placebo cholecalciferol: once daily orally for 2 months

Primary outcomes

  1. Proportion of pulmonary TB patients who are culture negative in sputum in week 4

    Time frame: week 4

    To determine the proportion of sputum culture positive patients becoming culture negative at 1 and 2 months after adjunctive sodium phenylbutyrate and vitamin D treatment of patients for 2 months.

  2. Difference in improvement in clinical endpoints consisting of cough clearance, percentage chest x-ray clearance, fever remission and weight increase upto 8 weeks.

    Time frame: 8 weeks

    Difference in improvement in clinical endpoints consisting of:

    cough clearance (weekly to week-8 then at week 24) chest x-ray impovement (percentage lung involvement on CXR at week 8) fever remission (weekly to week-8 then at week 24) weight increase (weekly to week-8 then at week 24)

Secondary outcomes

  1. Sputum smear conversion time

    Time frame: weekly up to week 12; then at week 24

  2. Radiological improvement (percent lung involvement on CXR)

    Time frame: week 0, 8, 12 and 24

  3. Cough clearance

    Time frame: weekly up to week 12; then at week 24

  4. Weight gain

    Time frame: weekly up to week 12, then at week 24

  5. Change in plasma PBA concentrations

    Time frame: week 0, 4, 8, 12

  6. Change in plasma 25(OH)D3 concentration

    Time frame: week 0, 4, 8, 12, 24

  7. Clinical failure and default independently and 'death or clinical failure or default'

    Time frame: week 24

  8. Hypercalcaemia (serum calcium > 2.6 mmol/L)

    Time frame: week 0, 2, 4, 8, 12

  9. Gastrointestinal side effects

    Time frame: weekly to week 12 then at week 24

  10. Immunological improvement (LL-37 in macrophages)

    Time frame: week 0, 4, 8, 12

  11. Functional immunological improvement (killing by macrophages)

    Time frame: week 0, 4, 8, 12

Sponsors and collaborators

Lead sponsor

International Centre for Diarrhoeal Disease Research, Bangladesh

Other

Collaborators

  • Karolinska Institutet
  • National Institute of Diseases of the Chest and Hospital, Bangladesh
  • University of Iceland

Registry information

Official study title

Clinical Trial of Oral Phenylbutyrate and Vitamin D Adjunctive Therapy in Pulmonary Tuberculosis in Bangladesh: a Pilot Study

Important dates

Study start
2010
Primary completion
2014
Study completion
2014
First posted
Apr 18, 2012
Registry last updated
Feb 13, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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