Effects of Adjunct Omega-3 Long-chain Polyunsaturated Fatty Acids in Pulmonary Tuberculosis Patients: An Early Bactericidal Activity and Inflammatory Activity Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 3
- 主要终点
- Sputum culture time to positive
研究概览
简要总结
The goal of this randomized controlled trial is to evaluate the early bactericidal activity, early inflammatory response, and safety of omega-3 long chain polyunsaturated fatty acid (n-3 PUFA) supplementation in adult patients (aged 18- 45 years) with newly diagnosed, bacteriologically confirmed drug-sensitive pulmonary tuberculosis.
The main questions it aims to answers are:
- Does adjunct n-3 LCPUFA supplementation reduce the sputum culture time to positivity
- Does it improve inflammatory markers and TB treatment outcomes compared to placebo Researchers will compare daily supplementation with ~2g n-3 LCPUFA (EPA and DHA ) to placebo (high linoleic sunflower oil) to determine effects on bactericidal activity, inflammation, and clinical outcomes.
Participants will:
- Be randomly assigned to receive either n-3 LCPUFA or Placebo daily for 8 weeks with the intensive phase of TB treatment
- Attend clinical visit baseline, and follow up visit mostly weekly for 2 months and then monthly for 4 months of the continuous phase of TB treatment
- Provide blood, sputum and urine samples for biomarkers and metabolomic analysis
- Undergo assessments of iron status, body composition and muscle strength
详细描述
Anti-inflammatory omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) supplementation results in improvement of infectious respiratory conditions, yet little evidence in patients with pulmonary tuberculosis (TB) exists. Animal studies have shown that adjunct n-3 LCPUFA optimized treatment outcomes by resolving inflammation, improving immune response, and mitigating iron deficiency and anaemia of inflammation.
This randomized controlled early bactericidal activity (EBA), early inflammatory activity (EIA), and safety trial among patients with newly bacteriologically confirmed adult drug-sensitive pulmonary TB patients (DS-TB), aged 18 - 45 years (n = 40), will investigate the clinical and anti-inflammatory effects of n-3 LCPUFA adjunct treatment for two months.
Patients presenting at Tshepong Hospital, Klerksdorp, North West Province, will receive either ~2 g n-3 LCPUFA (eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA)) or placebo (high-linoleic sunflower oil) daily for two months. The primary outcome is sputum culture time to positivity. Secondary outcomes include time to stable culture conversion, proportion of participants converted at 8 weeks, inflammatory markers and safety. Exploratory objectives include iron status, body composition and muscle strength, clinical outcomes, microbial translocation biomarkers, resting energy expenditure, fatty acid composition, plasma lipid mediators, and related metabolomics and gene expression.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •adults aged 18-45 years
- •laboratory confirmed Pulmonary TB defined as a hard copy of a sputum result detected by WHO recommended assay or mycobacteria culture.
- •Women of childbearing potential with a negative pregnancy test on enrollment
- •All participant irrespective of HIV status who consent to have a HIV test during enrollment.
排除标准
- •Comorbid condition with treatment of NSAIDS is indicated
- •Institutionalized or incarcerated individuals
- •Those on Multiple drug resistance treatment for more than 4 days within the past 6 months or within 1 month to prior to TB treatment initiation
- •Pregnant or breastfeeding women or women who become pregnant in the first 4 weeks of the trial will be withdrawn
- •show lab safety values: AST or ALT > x3 upper limit of normal (ULN) or Total bilirubin > 2x the ULN, Neutrophils ≤ 700/mm³, Platelets < 50,000/mm³, Haemoglobin < 8 g/dL, Serum creatinine > 2× ULN.
- •Are receiving or planning treatment with any of the following in the 3 months before or during the trial:
- •Anticoagulants Immune-modulating therapy (e.g., cancer treatment, oral/inhaled corticosteroids) Antacids or proton pump inhibitors (PPIs)
- •Have a known allergy or sensitivity to fish or fish oil.
- •Have a recent history (within 2 years) or current clinical evidence of:
- •Peptic ulcer disease or GI bleeding Coagulopathy or bleeding disorders Kidney or liver disease requiring hospitalisation Cardiovascular disease or significant risk factors for it
- •Are HIV-positive and meet any of the following: CD4 count < 100 cells/mm³ Viral load > 400 copies/mL (if on ART) Not yet on ART but are expected to initiate treatment during the 8-week intervention phase
- •Report high-risk alcohol use (average >4 units/day or binge drinking patterns)
- •Have any other medical condition or situation that, in the investigator's opinion, may interfere with protocol adherence or data interpretation.
- •Plan to relocate from the study area within the next 3 months.
- •Are currently using omega-3 or omega-6 supplements and are unwilling to stop for the duration of the study.
研究组 & 干预措施
High Linoleic sunflower oil
The placebo group will also consist of 20 participant randomized and stratified for sex, HIV status. They will also receive 3 1g capsules of high linoleic sunflower oil that has been encapsulated using the specification and dimension of the omega 3 real thing capsules to closely match the intervention
干预措施: Placebo (Dietary Supplement)
Omega 3 Long chain Polyunsaturated fatty acid
20 Participant will be in this arm, randomized for sex and HIV status. Participant in the intervention group will receive 3- 1g fish oil capsules capsules to take with their TB treatment of Omega 3 (real thing mega omega supreme). These capsules provide approximately 2g of EPA and DHA
干预措施: Omega-3 (EPA+DHA) (Dietary Supplement)
结局指标
主要结局
Sputum culture time to positive
时间窗: TTP will be measured on the following days of the intervention: day 1, day 4, day 7, day 14, day 21, day 30 and day 60
which is defined as the number of hours between sample inoculation and the detection of microbial growth , A shorter detection time shows that intervention is not working and there is still a higher bacterial load in sputum whilst longer detection time shows improvement in treatment and thus effective intervention
次要结局
- time to stable culture conversion(Sputum cultures to measure time to stable culture conversion will be measured on days: 1,4,7,14,21,30 and 60)
- Proportion of participants with stable sputum culture conversion(sputum cultures will be collected at day 1, day 4, day 7, day 14, day 21, day 30 and day 60)
- Safety measures(baseline, day 7, day 30 and day 60)
研究者
Linda Malan
Prof
North-West University, South Africa