Phase 3 Trial of Oral L-arginine and / or Vitamin D as Adjunctive Therapies in Pulmonary Tuberculosis in Papua Province, Indonesia.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Proportion of pulmonary TB patients who are culture negative at 1 month
研究概览
简要总结
The purpose of this study is to determine whether adjunctive L-arginine and vitamin D can improve response to standard short course TB therapy in people with newly diagnosed pulmonary TB.
详细描述
The two major pathways proposed to mediate macrophage mycobacterial killing in humans are the arginine-nitric oxide and Vitamin D-1,25 dihydroxyvitamin D pathways. Our aim is to determine if the key immunomodulatory agents L-arginine and vitamin D can improve the rapidity and magnitude of the microbiological and clinical response in pulmonary TB. We will test the following hypotheses in newly-diagnosed TB patients in Timika, Papua, Indonesia:
Our specific aims are to:
- Determine whether supplementation with L-arginine and/or vitamin D is safe, and results in more rapid improvement in clinical, mycobacterial, immunological, radiological, physiological and functional measures of treatment outcome. We will randomise patients with pulmonary TB to receive, in addition to standard TB therapy, adjunctive arginine, vitamin D and / or placebo in a randomised, double-blind factorial 2x2 design. We will relate serial measurements of plasma concentrations of L-arginine and vitamin D, and immunological responses (pulmonary NO production, T cell function and phenotype) to measures of treatment outcome [mycobacterial (sputum smear clearance and culture conversion), physiological (spirometry), clinical (symptoms and weight), radiological (chest Xray) and functional (six-minute walk test, modified St George Respiratory Questionnaire)].
- Determine whether pulmonary production of NO is inversely related to disease severity at presentation. Baseline and serial measures of NO production will be related to disease severity and the magnitude and rapidity of clinical response
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
- 15 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults >15 years with sputum smear positive pulmonary TB
- •New cases only
- •Agree to continue treatment in Timika for the full six month course of treatment -Not pregnant
- •Consent to enroll in the study.
排除标准
- •hypercalcaemia (ionized calcium >1.32 mmol/L) identified at baseline
- •taking arginine or vitamin D
研究组 & 干预措施
1
Active L-arginine plus active vitamin D
干预措施: L-arginine (Drug)
1
Active L-arginine plus active vitamin D
干预措施: Vitamin D (Drug)
2
Placebo L-arginine plus active Vitamin D
干预措施: Vitamin D (Drug)
2
Placebo L-arginine plus active Vitamin D
干预措施: Placebo L-arginine (Drug)
3
Active L-arginine plus placebo vitamin D
干预措施: L-arginine (Drug)
3
Active L-arginine plus placebo vitamin D
干预措施: Placebo Vitamin D (Drug)
4
placebo L-arginine plus placebo vitamin D
干预措施: Placebo L-arginine (Drug)
4
placebo L-arginine plus placebo vitamin D
干预措施: Placebo Vitamin D (Drug)
结局指标
主要结局
Proportion of pulmonary TB patients who are culture negative at 1 month
时间窗: 1 month
Difference in improvement in composite clinical endpoint comprising weight, cough clearance and FEV1 at 2 months.
时间窗: 2 months
次要结局
- Hypercalcaemia(week 0, 2, 4, 8, 24)
- Functional improvement measured using six minute walk test(week 0, 4, 8, 24)
- Quality of life assessment using modified St George Respiratory Questionnaire.(weeks 0, 4, 8, 24)
- Change in plasma L-arginine concentration(week 0, 2, 4, 8, 24)
- Change in plasma 25(OH)D3 concentration(week 0, 2, 4, 8, 24)
- Death, clinical failure and default independently, and 'death or clinical failure or default'.(week 24)
- Gastrointestinal side effects(weekly to week 8 then at week 24)
- Sputum smear conversion time(weekly to week 8 then at week 24)
- Radiological improvement (percentage lung involvement on CXR at 2 months).(week 0, 2, 4, 8, 24)
- Cough clearance(weekly to week 8 then at week 24)
- Difference in improvement in percent predicted FEV1 at 2 and 6 months.(weeks 0, 4, 8, 24)
- Weight gain(weekly to week 8 then at week 24)
- Immunological improvement (exhaled NO)(week 0, 2, 4, 8, 24)
- Immunological improvement (T cell CD3ζ expression and T cell function)(week 0, 2, 4, 24)
- Primary end points stratified by HIV status.(weekly to week 8 then at week 24)
- Primary end points stratified by baseline vitamin D and L-arginine status.(weekly to week 8 then week 24)
- Primary end points stratified by ethnicity (Papuan and non-Papuan patients).(weekly to week 8 then week 24)
研究者
Dr Anna Ralph
Global and Tropical Health
Menzies School of Health Research