Acute Exacerbation Chronic Obstructive Pulmonary DiseasePhase 3NCT07456176
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
A Phase 3 study testing Alpha Lipoic Acid 600 MG Oral Tablets and Alpha Lipoic Acid in people with Acute Exacerbation Chronic Obstructive Pulmonary Disease, run by Ain Shams University at 1 site in Egypt.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Acute Exacerbation Chronic Obstructive Pulmonary Disease
- What is being tested?
- Alpha Lipoic Acid 600 MG Oral Tablets and Alpha Lipoic Acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 1 siteEgypt
- Study dates
- 28 Feb 2026to 1 Jun 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- • 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).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Egypt1 site
Matareya Teaching Hospital
Cairo, 11856
Amir Eskander Hanna, MD, +201227933624, amireskanderhanna@gmail.com
Mariam Elsayed, Bachelor of Pharmacy
About this study
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.
Read more
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.
Read the detailed description
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.
Safety monitoring will include assessment of known potential adverse effects associated with ALA, including gastrointestinal symptoms, hypoglycemia, neurological manifestations, and hypersensitivity reactions. All adverse events will be recorded and evaluated for severity and causality.
The sample size has been calculated to detect clinically meaningful differences in oxidative stress markers between groups with 90% statistical power, accounting for multiple comparisons. Statistical analyses will be conducted using an intention-to-treat approach with appropriate adjustments for multiple testing.
This study aims to provide randomized clinical evidence on the efficacy and dose-dependent effects of alpha-lipoic acid as an adjunctive therapy in acute exacerbations of COPD, targeting the oxidative-inflammatory pathway to improve biochemical and clinical outcomes.
- Being tested
- Alpha Lipoic Acid 600 MG Oral Tablets, Alpha Lipoic Acid, Placebo
- Keywords
- Acute exacerbations of COPD, Alpha lipoic acid, adjuvant therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alpha Lipoic Acid 600 MG Oral TabletsDrug
Alpha lipoic acid tablets 600 mg
Alpha Lipoic AcidDrug
Alpha lipoic acid tablets 1200 mg
PlaceboDrug
Patients in this group will receive standard therapy for AECOPD along with matching placebo capsules administered orally for 10 days.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Oxidative Stress & Inflammatory Biomarkers
- Malondialdehyde (MDA)
- Interleukin-8 (IL-8)
Measured: Measured at baseline (Day 0) and Day 10
Secondary outcomes (3)
Length of hospital stay
Measured: 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
The COPD Assessment Test (CAT) is a simple, validated 8-item questionnaire used to assess the impact of Chronic Obstructive Pulmonary Disease on a patient's health status and daily life.
Measured: It will be assessed at baseline of the study and after 10 days
Clinical stability
Clinical stability: Defined as the time from initiation of the study intervention until the patient achieves clinical stability, characterized by meeting all of the following criteria and maintaining them for at least 24 consecutive hours:
- Resolution of fever: Temperature ≤ 37.5°C
- Stable hemodynamics: Heart rate ≤ 100 beats/min and systolic blood pressure ≥ 90 mmHg
- Stable respiratory status: Respiratory rate ≤ 24 breaths/min
- Improved oxygenation: Oxygen saturation ≥ 90% on room air or stable supplemental oxygen (or baseline if known to be lower)
- No need for rescue medications beyond the scheduled regimen
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2026
- Study start28 Feb 2026 (estimated)
- Primary completion28 May 2026 (estimated)
- Study completion1 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Exacerbation Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- More trials run by Ain Shams UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 75 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ain Shams University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Eman Mohamed El Mokadem, Ain Shams University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07456176
- Sponsor's protocol ID
- HM000218
- Status last verified
- Feb 2026
- First submitted
- 26 Feb 2026
- Last updated
- 30 Mar 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07456176
- Acronym / sponsor ID
- HM000218
- Keywords
- Acute exacerbations of COPD, Alpha lipoic acid, adjuvant therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- Ain Shams UniversityUniversity, hospital or other
- Study start
- 28 Feb 2026 (estimated)
- Primary completion
- 28 May 2026 (estimated)
- Study completion
- 1 Jun 2026 (estimated)
- First posted
- 6 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Safety monitoring will include assessment of known potential adverse effects associated with ALA, including gastrointestinal symptoms, hypoglycemia, neurological manifestations, and hypersensitivity reactions. All adverse events will be recorded and evaluated for severity and causality.
The sample size has been calculated to detect clinically meaningful differences in oxidative stress markers between groups with 90% statistical power, accounting for multiple comparisons. Statistical analyses will be conducted using an intention-to-treat approach with appropriate adjustments for multiple testing.
This study aims to provide randomized clinical evidence on the efficacy and dose-dependent effects of alpha-lipoic acid as an adjunctive therapy in acute exacerbations of COPD, targeting the oxidative-inflammatory pathway to improve biochemical and clinical outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Low dose Alpha lipoic acid | Active comparator | Drug: Alpha Lipoic Acid 600 MG Oral TabletsPatients in this group will receive standard AECOPD therapy in addition to 600 mg of oral ALA per day for 10 days |
| High dose Alpha lipoic acid | Active comparator | Drug: Alpha Lipoic AcidPatients in this group will receive standard AECOPD therapy in addition to 1200 mg of oral ALA per day for 10 days |
| Placebo | Placebo comparator | Drug: PlaceboPatients in this group will receive standard therapy for AECOPD along with matching placebo capsules administered orally for 10 days. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (5 listed)
- • Known allergy or intolerance to ALA.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Alpha Lipoic Acid 600 MG Oral TabletsAlpha lipoic acid tablets 600 mg | Drug | Low dose Alpha lipoic acid |
| Alpha Lipoic AcidAlpha lipoic acid tablets 1200 mg | Drug | High dose Alpha lipoic acid |
| PlaceboPatients in this group will receive standard therapy for AECOPD along with matching placebo capsules administered orally for 10 days. | Drug | Placebo |
Primary outcome
Oxidative Stress & Inflammatory Biomarkers
Time frame: Measured at baseline (Day 0) and Day 10
* Malondialdehyde (MDA) * Interleukin-8 (IL-8)
3 secondary outcomes
Length of hospital stay
Time frame: 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
Time frame: It will be assessed at baseline of the study and after 10 days
Clinical stability
Time frame: 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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Alpha Lipoic Acid 600 MG Oral Tablets and Alpha Lipoic Acid in people with Acute Exacerbation Chronic Obstructive Pulmonary Disease, run by Ain Shams University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 30 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Oxidative Stress & Inflammatory Biomarkers (time frame: Measured at baseline (Day 0) and Day 10). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2026.