Effect of Low-Dose Versus High-Dose Alpha-Lipoic Acid on Oxidative Stress, Inflammation, and Clinical Outcomes in Acute Exacerbations of Chronic Obstructive Pulmonary Disease
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 75
- 试验地点
- 1
- 主要终点
- Oxidative Stress & Inflammatory Biomarkers
研究概览
简要总结
Chronic Obstructive Pulmonary Disease (COPD) is a progressive inflammatory lung disease characterized by persistent airflow limitation and enhanced oxidative stress. Acute exacerbations of COPD (AECOPD) significantly increase morbidity, accelerate lung function decline, and worsen clinical outcomes. Oxidative stress plays a central role in AECOPD pathophysiology by amplifying inflammation through mediators such as IL-8 and TNF-α, leading to airway injury and impaired gas exchange.
Alpha Lipoic Acid (ALA) is a potent antioxidant and anti-inflammatory agent that scavenges reactive oxygen species, regenerates endogenous antioxidants, and modulates redox-sensitive inflammatory pathways. Although preclinical evidence supports its protective role in respiratory diseases, no randomized clinical trial has evaluated ALA in AECOPD or compared different dosing strategies.
Aim
This study aims to evaluate and compare the effects of low-dose (600 mg/day) versus high-dose (1200 mg/day) ALA on oxidative stress markers, inflammatory biomarkers, clinical recovery, pulmonary oxygenation, gas exchange, and safety in patients with AECOPD.
Methods
This is a prospective, double-blind, randomized controlled trial conducted in the ICU at El Matareya Teaching Hospital. Adult patients (40-70 years) with confirmed COPD and frequent exacerbations were randomized (1:1:1) into three groups:
Group A: Standard therapy + placebo
Group B: Standard therapy + 600 mg/day oral ALA
Group C: Standard therapy + 1200 mg/day oral ALA
All patients received guideline-based AECOPD management according to GOLD recommendations, including bronchodilators, systemic corticosteroids, antibiotics (when indicated), oxygen therapy, and ventilatory support as needed.
Assessments
Baseline and Day 10 evaluations included:
Primary Outcomes:
Oxidative stress marker: Malondialdehyde (MDA)
Inflammatory markers: Interleukin-8 (IL-8) and C-reactive protein (CRP)
Secondary Outcomes:
Time to clinical stability
ICU and hospital length of stay
Need for non-invasive or invasive ventilation
Early relapse (14 days) and 30-day readmission
Gas Exchange: ABGs (pH, PaO₂, PaCO₂, P/F ratio)
Patient-Reported Outcomes: COPD Assessment Test (CAT) and mMRC dyspnea scale
Safety: Monitoring for adverse effects including gastrointestinal symptoms, hypoglycemia, dizziness, and hypersensitivity reactions.
详细描述
Acute exacerbations of chronic obstructive pulmonary disease (COPD) are characterized by an acute intensification of airway inflammation and oxidative stress, resulting in worsening airflow limitation, impaired gas exchange, and increased risk of morbidity and healthcare utilization. Oxidative stress is a key contributor to exacerbation pathophysiology, driven by excess generation of reactive oxygen species, depletion of endogenous antioxidant defenses, activation of redox-sensitive transcription pathways, and upregulation of pro-inflammatory mediators. These processes promote neutrophilic airway inflammation, epithelial damage, mucus hypersecretion, and decline in pulmonary function.
Alpha-lipoic acid (ALA) is an endogenous mitochondrial cofactor with established antioxidant and anti-inflammatory properties. It functions through redox cycling, direct scavenging of reactive oxygen species, regeneration of intracellular antioxidants (including glutathione), and modulation of redox-sensitive signaling pathways involved in inflammation. Although preclinical studies have demonstrated protective effects of ALA in models of oxidative lung injury, its clinical role in acute exacerbations of COPD has not been established.
This study is a prospective, randomized, double-blind, placebo-controlled, parallel-group clinical trial evaluating the adjunctive use of ALA in patients hospitalized with acute exacerbations of COPD. Participants will be randomized in a 1:1:1 ratio to receive placebo, ALA 600 mg/day, or ALA 1200 mg/day for 10 days, in addition to standard-of-care therapy in accordance with current guideline-based management. The intervention period aligns with the typical duration of acute-phase pharmacologic treatment and is intended to capture early biochemical and clinical responses.
The trial is designed to assess potential dose-response effects by comparing two dosing regimens of ALA against placebo under standardized treatment conditions. Randomization will be computer-generated with allocation concealment ensured through identical-appearing study medications to maintain blinding of participants, healthcare providers, and outcome assessors.
The primary objective is to evaluate the effect of adjunctive ALA on systemic oxidative stress and inflammatory biomarkers during the acute treatment period. Secondary objectives include assessment of clinical recovery parameters, respiratory function and gas exchange indices, symptom burden, healthcare utilization, and safety outcomes. Time to clinical stability will be evaluated using predefined objective physiological criteria.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •- Confirmed diagnosis of COPD, supported by a previous spirometry report showing: Post-bronchodilator FEV₁/FVC < 0.70, consistent with GOLD criteria for persistent airflow limitation.
- •History of frequent exacerbations, defined as two or more COPD exacerbations per year during the two years prior to enrollment.
- •An exacerbation of COPD is an acute event characterized by increased dyspnea and/or cough and sputum that worsens within ≤14 days and often results in additional therapy, according to the most recent GOLD guidelines.
排除标准
- •• Known allergy or intolerance to ALA.
- •Cystic fibrosis or bronchiectasis.
- •Patients with a history of asthma, pneumonia, interstitial lung disease, bronchiectasis, carcinoma of the bronchus, or other significant respiratory disease
- •Active or recent infection with tuberculosis.
- •Any other significant comorbid condition that could interfere with study participation or outcomes (e.g., severe liver or kidney disease, uncontrolled cardiovascular disease).
研究组 & 干预措施
Low dose Alpha lipoic acid
Patients in this group will receive standard AECOPD therapy in addition to 600 mg of oral ALA per day for 10 days
干预措施: Alpha Lipoic Acid 600 MG Oral Tablets (Drug)
High dose Alpha lipoic acid
Patients in this group will receive standard AECOPD therapy in addition to 1200 mg of oral ALA per day for 10 days
干预措施: Alpha Lipoic Acid (Drug)
Placebo
Patients in this group will receive standard therapy for AECOPD along with matching placebo capsules administered orally for 10 days.
干预措施: Placebo (Drug)
结局指标
主要结局
Oxidative Stress & Inflammatory Biomarkers
时间窗: Measured at baseline (Day 0) and Day 10
* Malondialdehyde (MDA) * Interleukin-8 (IL-8)
次要结局
- Length of hospital stay(From the date of randomization until hospital discharge, assessed during the index hospitalization for up to 30 days after randomization.)
- COPD Assessment Test (CAT) score(It will be assessed at baseline of the study and after 10 days)
- Clinical stability(From the date of randomization until the date clinical stability is first achieved and maintained for at least 24 consecutive hours, assessed daily during hospitalization for up to 10 days after randomization.)
研究者
Eman Mohamed El Mokadem
Lecturer of Pharmacy Practice and Clinical Pharmacy
Ain Shams University