Clinical Trial of Oral Phenylbutyrate and Vitamin D Adjunctive Therapy in Pulmonary Tuberculosis in Bangladesh: a Pilot Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 288
- 试验地点
- 1
- 主要终点
- Proportion of pulmonary TB patients who are culture negative in sputum in week 4
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults, 18-60 years with sputum smear positive pulmonary TB
- •New cases only
- •Gender, both
- •Consent to enroll in the study
排除标准
- •Hypercalcaemia (serum calcium > 2.6 mmol/L) identified at baseline
- •Taking vitamin D
- •Pregnant and lactating
- •Any known liver or kidney function abnormality, malignancy
研究组 & 干预措施
Active Sodium Phenylbutyrate and active cholecalciferol
500 mg sodium phenylbutyrate (4-phenylbutyric acid, sodium salt) in tablet form twice daily and 5000 IU of cholecalciferol once daily will be given orally for 2 months
干预措施: Active Sodium Phenylbutyrate and active cholecalciferol (Drug)
Placebo Sodium Phenylbutyrate plus active cholecalciferol
Drug: Cholecalciferol Placebo: Sodium Phenylbutyrate
干预措施: Placebo Sodium Phenylbutyrate plus active cholecalciferol (Drug)
Active Sodium Phenylbutyrate and placebo cholecalciferol
Drug: Sodium Phenylbutyrate Placebo: cholecalciferol
干预措施: Active Sodium Phenylbutyrate and placebo cholecalciferol (Drug)
Placebo Sodium Phenylbutyrate plus placebo cholecalciferol
Placebo Sodium Phenylbutyrate Placebo cholecalciferol
干预措施: Placebo Sodium Phenylbutyrate plus placebo cholecalciferol (Drug)
结局指标
主要结局
Proportion of pulmonary TB patients who are culture negative in sputum in week 4
时间窗: 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.
Difference in improvement in clinical endpoints consisting of cough clearance, percentage chest x-ray clearance, fever remission and weight increase upto 8 weeks.
时间窗: 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)
次要结局
- Change in plasma 25(OH)D3 concentration(week 0, 4, 8, 12, 24)
- Gastrointestinal side effects(weekly to week 12 then at week 24)
- Radiological improvement (percent lung involvement on CXR)(week 0, 8, 12 and 24)
- Cough clearance(weekly up to week 12; then at week 24)
- Weight gain(weekly up to week 12, then at week 24)
- Sputum smear conversion time(weekly up to week 12; then at week 24)
- Hypercalcaemia (serum calcium > 2.6 mmol/L)(week 0, 2, 4, 8, 12)
- Immunological improvement (LL-37 in macrophages)(week 0, 4, 8, 12)
- Functional immunological improvement (killing by macrophages)(week 0, 4, 8, 12)
- Change in plasma PBA concentrations(week 0, 4, 8, 12)
- Clinical failure and default independently and 'death or clinical failure or default'(week 24)