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

NCT07456176 | Not Yet Recruiting Phase 3

• 1 other identifier: HM000218
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Exacerbation Chronic Obstructive Pulmonary Disease

Keywords

Acute exacerbations of COPD; Alpha lipoic acid; adjuvant therapy

Outcome Measures

Primary Outcomes (1)

• Oxidative Stress & Inflammatory Biomarkers

  * Malondialdehyde (MDA) * Interleukin-8 (IL-8)

  Measured at baseline (Day 0) and Day 10

Secondary Outcomes (3)

• 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.

Study Arms (3)

Low dose Alpha lipoic acid

ACTIVE COMPARATOR

Patients in this group will receive standard AECOPD therapy in addition to 600 mg of oral ALA per day for 10 days

Drug: Alpha Lipoic Acid 600 MG Oral Tablets

High dose Alpha lipoic acid

ACTIVE COMPARATOR

Patients in this group will receive standard AECOPD therapy in addition to 1200 mg of oral ALA per day for 10 days

Drug: Alpha Lipoic Acid

Placebo

PLACEBO COMPARATOR

Patients in this group will receive standard therapy for AECOPD along with matching placebo capsules administered orally for 10 days.

Drug: Placebo

Interventions

Alpha Lipoic Acid 600 MG Oral Tablets DRUG

Alpha lipoic acid tablets 600 mg

Low dose Alpha lipoic acid

Alpha Lipoic Acid DRUG

Alpha lipoic acid tablets 1200 mg

High dose Alpha lipoic acid

Placebo DRUG

Patients in this group will receive standard therapy for AECOPD along with matching placebo capsules administered orally for 10 days.

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (1)

Matareya Teaching Hospital

Cairo, 11856, Egypt

Location

MeSH Terms

Interventions

Thioctic Acid

Intervention Hierarchy (Ancestors)

Carboxylic Acids; Organic Chemicals; Thiophenes; Sulfur Compounds; Coenzymes; Enzymes and Coenzymes; Fatty Acids; Lipids

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer of Pharmacy Practice and Clinical Pharmacy

Study Record Dates

• First Submitted: February 26, 2026
• First Posted: March 6, 2026
• Study Start: February 28, 2026
• Primary Completion (Estimated): May 28, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: March 30, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)