Clinical Trial of Phenylbutyrate and Vitamin D in Tuberculosis (TB)
Condition: Pulmonary Tuberculosis
MeSH terms: Tuberculosis; Tuberculosis, Pulmonary
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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:

        1. Can improve response to standard short course TB therapy towards a rapid recovery
           (clinical, radiological, mycobacterial).

        2. Can induce expression of LL-37 in macrophages (immunological).

        3. 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
    

Intervention name(s): Active Sodium Phenylbutyrate and active cholecalciferol; Placebo Sodium Phenylbutyrate plus active cholecalciferol; Active Sodium Phenylbutyrate and placebo cholecalciferol; Placebo Sodium Phenylbutyrate plus placebo cholecalciferol
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Sodium Phenylbutyrate: 500 mg twice daily orally for 2 months Cholecalciferol: 5000 IU once daily orally for 2 months; Placebo Sodium Phenylbutyrate: twice daily orally for 2 months Cholecalciferol: 5000 IU once daily for 2 months; Sodium phenylbutyrate: 500 mg twice daily orally for 2 months Placebo cholecalciferol: once daily orally for 2 months; Placebo Sodium Phenylbutyrate: twice daily orally for 2 months Placebo cholecalciferol: once daily orally for 2 months
Other intervention name(s): triButyrate®; Vigantol oil; Vigantol oil; Placebo Phenylbutyrate; triButyrate®; Placebo vigantol oil
Intervention MeSH terms: Cholecalciferol; Vitamin D; 4-phenylbutyric acid
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: tuberculosis; phenylbutyrate; vitamin D; cathelicidin; antimicrobial peptide; in adults