Effects of Lipoic Acid on Oxidative, Inflammatory and Functional Markers in Asthmatic Patients

• Sponsor: Centro Universitario de Ciencias de la Salud, Mexico (Other)
• Overall Status: Completed
• CT.gov ID: NCT01221350
• Collaborator: National Council of Science and Technology, Mexico (Other), University of Guadalajara (Other), Hospital Civil Juan I. Menchaca (Other)
• Enrollment: 55
• Locations: 2
• Arms: 2
• Duration (Months): 21
• Patients Per Site: 27.5
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

The aim of the study is to use the antioxidant and antiinflammatory effects of lipoic acid to improve the quality of life of patients with asthma.

The investigators will administrate 600 mg lipoic acid orally on a daily basis during two months concurrent with the patient anti-asthmatic therapy and evaluate the effects on resulting pulmonary function, inflammatory and oxidative stress biomarkers and health-related quality of life previous to the initial of the treatment and at 60 days of the supplementary therapy.

Condition or Disease	Intervention/Treatment	Phase
Asthma; Allergic Rhinitis	Dietary Supplement: Lipoic acid; Dietary Supplement: Placebo	N/A

Detailed Description

Asthma is an inflammatory disease of high prevalence around the world. During development of asthma the presence of oxidative stress has been related to susceptibility and severity of the disease, thus making the use of antioxidant adjuvant therapy with lipoic acid (LA) an interesting treatment option. The objective of the study is to evaluate the efficacy of LA as an adjuvant treatment on functional, antioxidant, inflammatory, quality and control parameters of asthma in human subjects. The trial design is a randomized, double blind, placebo controlled parallel study.

Adult patients (>18 years) with history of mild intermittent to moderate asthma according to the Global Initiative for Asthma (GINA) guidelines were enrolled. It was required a positive skin prick test (>3 mm) for at least two regional allergens. Patients were randomly assigned to receive lipoic acid or placebo for 60 days. Participants had an intermediate visit to the attending physician one month after initial of treatment to monitor adverse events and to undergo laboratory tests.

1. Introduction. Asthma is an inflammatory disease of high prevalence around the world. During development of asthma the presence of oxidative stress has been related to susceptibility and severity of the disease, thus making the use of antioxidant adjuvant therapy with lipoic acid (LA) an interesting treatment option.

2. Study design. A randomized, double blind, placebo controlled parallel study

3. Methods. Participants and interventions: 55 patients with mild to moderate asthma from Hospital Civil "Juan I. Menchaca" in Guadalajara, Jalisco, México were included and randomized in block of 10 to receive; LA (600 mg/day) or placebo for eight weeks from January to October of 2011.

4. Objective. To evaluate the efficacy of LA as an adjuvant treatment on functional, antioxidant, inflammatory, quality and control parameters of asthma in human subjects. Primary outcome: change on Forced expiratory volume in 1 second (FEV1), secondary outcomes were levels of Oxygen radical absorbance capacity (ORAC), glutathione (GSH), glutathione disulfide (GSSG), protein carbonyls, differential count of sputum cells, interleukin-4 (IL-4) and scores of quality of life and control of asthma questionnaires.

Study Design

• Study Type: Interventional
• Actual Enrollment: 55 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: Exploratory Study of Lipoic Acid Supplementation on Oxidative Stress, Inflammatory and Functional Markers in Asthmatic Patients: Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Clinical Trial.
• Study Start Date: Nov 1, 2010
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lipoic acid Lipoic acid 600 mg oral dose (two 300 mg capsules) once daily in the morning during 60 days	Dietary Supplement: Lipoic acid; Lipoic acid 600 mg dose (two 300 mg capsules) once daily in the morning. All patients continued their asthma treatments given by their primary care physician also they were allowed to use rescue medication on demand consisting in inhaled salbutamol. During basal and 8 weeks visits spirometry with bronchodilator challenge, sputum induction and quality of life questionnaires and asthma control test were performed.; Other Names: Thioctic Acid Alpha-Lipoic Acid
Placebo Comparator: Placebo Placebo (two placebo capsules) orally once daily in the morning during 60 days	Dietary Supplement: Placebo; Placebo (two capsules filled with 300 mg vehicle) once daily in the morning during 60 days. All patients continued their asthma treatments given by their primary care physician also they were allowed to use rescue medication on demand consisting in inhaled salbutamol. During basal and 8 weeks visits spirometry with bronchodilator challenge, sputum induction and quality of life questionnaires and asthma control test were performed; Other Names: Placebos Placebo effect

Outcome Measures

Primary Outcome Measures

1. Spirometric FVC Values at Baseline [Baseline]

   Measurement of spirometric predicted parameters at baseline. Forced vital capacity (FVC) is the volume of air that can forcibly be blown out after full inspiration, measured in liters.

2. Spirometric FVC Values at Endpoint [60 days]

   Measurement of spirometric predicted parameters at the baseline and after 60 days of treatment: Forced vital capacity (FVC) is the volume of air that can forcibly be blown out after full inspiration, measured in liters.

3. Spirometric FEV1 Values at Baseline [Baseline]

   Measurement of spirometric predicted parameters at baseline: Forced expiratory volume in 1 second (FEV1), volume that has been exhaled at the end of the first second of forced expiration.

4. Spirometric FEV1 Values at Endpoint [60 days]

   Measurement of spirometric predicted parameters after 60 days of treatment. Forced expiratory volume in 1 second (FEV1), volume that has been exhaled at the end of the first second of forced expiration.

5. Spirometric FEF Values at Baseline [Baseline]

   Measurement of spirometric parameters at baseline: Forced expiratory flow (FEF) is the flow (or speed) of air coming out of the lung during the middle portion of a forced expiration.

6. Spirometric FEF Values at Endpoint [60 days]

   Measurement of spirometric FEF after 60 days of treatment: Forced expiratory flow (FEF) is the flow (or speed) of air coming out of the lung during the middle portion of a forced expiration.

Secondary Outcome Measures

1. Induced Sputum of Glutathione (GSH)/Glutathione Disulfide (GSSG) Ratio at Baseline [Baseline]

   Induced sputum of GSH and GSSG levels at baseline. The ratio GSH/GSSG is considered an index of antioxidant status and reductive -SH groups. GSH and GSSG were measured by a microplate fluorescent assay.

2. Induced Sputum of Glutathione (GSH)/Glutathione Disulfide (GSSG) Ratio at Endpoint [60 days]

   Change in the induced sputum of antioxidant parameters GSH and GSSG levels after 60 days of treatment. The ratio GSH/GSSG is considered an index of antioxidant status and reductive -SH groups. GSH and GSSG were measured by a microplate fluorescent assay.

3. Induced Sputum Carbonylated Proteins at Baseline [Baseline]

   Proteins can become modified by a large number of reactions involving reactive oxygen species. Among these, carbonylation is an irreversible and unrepairable oxidative reaction. The main protein modifications originated from oxidative stress comprise direct oxidation of aminoacids with a thiol group, such as cysteine, oxidative glycation, and carbonylation. Oxidative protein carbonylation induce protein degradation in a nonspecific manner. Chemically, oxidative carbonylation preferentially occurs at proline, threonine, lysine, and arginine, presumably through a metal-catalyzed activation of hydrogen peroxide to a reactive intermediate. Carbonylation usually refers to a process that forms reactive ketones or aldehydes that can be reacted by 2,4-dinitrophenylhydrazine (DNPH) to form hydrazones. Direct oxidation of side chains of lysine, arginine, proline, and threonine residues, among other aminoacids, produces DNPH detectable protein products

4. Induced Sputum Carbonylated Proteins at Endpoint [60 days]

   Proteins can become modified by a large number of reactions involving reactive oxygen species. Among these, carbonylation is an irreversible and unrepairable oxidative reaction. The main protein modifications originated from oxidative stress comprise direct oxidation of aminoacids with a thiol group, such as cysteine, oxidative glycation, and carbonylation. Oxidative protein carbonylation induce protein degradation in a nonspecific manner. Chemically, oxidative carbonylation preferentially occurs at proline, threonine, lysine, and arginine, presumably through a metal-catalyzed activation of hydrogen peroxide to a reactive intermediate. Carbonylation usually refers to a process that forms reactive ketones or aldehydes that can be reacted by 2,4-dinitrophenylhydrazine (DNPH) to form hydrazones. Direct oxidation of side chains of lysine, arginine, proline, and threonine residues, among other aminoacids, produces DNPH detectable protein products.

5. Induced Sputum Eosinophils at Baseline [Baseline]

   Eosinophils, a prominent feature of asthma, are found in increased numbers in the circulation and sputum, usually in relation to the severity of asthma.

6. Induced Sputum Eosinophils at Endpoint [60 days]

   Eosinophils, a prominent feature of asthma, are found in increased numbers in the circulation and sputum, usually in relation to the severity of asthma.

7. Inflammatory Interleukin-4 (IL-4) Sputum Levels at Baseline [Baseline]

   Inflammatory IL-4 sputum levels after 60 days of treatment. Sputum induction is a semi-invasive technique used to detect and monitor airway inflammation. IL-4 is a Th2 cytokine that promote airway inflammation in asthma. IL-4 drives the production of immunoglobulin E (IgE) in B cells. IL-4 was measured by ELISA.

8. Inflammatory IL-4 Sputum Levels at Endpoint [60 days]

   Inflammatory IL-4 sputum levels after 60 days of treatment. Sputum induction is a semi-invasive technique used to detect and monitor airway inflammation. IL-4 is a Th2 cytokine that promote airway inflammation in asthma. IL-4 drives the production of IgE in B cells. IL-4 was measured by ELISA.

9. Measurement of Quality of Life With the ACT (Asthma Control Test) at Baseline [Baseline]

   Assessment of Quality of life scores with the ACT (Asthma Control Test). The ACT is a way to determine if the asthma symptoms are well controlled. The Asthma Control Test™ (ACT™) is a five question health survey used to measure asthma control in individuals 12 years of age and older. The survey measures the elements of asthma control as defined by the National Heart, Lung, and Blood Institute (NHLBI). ACT is an efficient, reliable, and valid method of measuring asthma control, with or without, lung functioning measures such as spirometry. Each item includes 5 response options corresponding to a 5-point Likert-type rating scale. In scoring the ACT survey, responses for each of the 5 items are summed to yield a score ranging from 5 (poor control of asthma) to 25 (complete control of asthma).

10. Measurement of Quality of Life With the ACT (Asthma Control Test) at Endpoint [60 days]

    Assessment of Quality of life scores with the ACT (Asthma Control Test). The ACT is a way to determine if the asthma symptoms are well controlled. The Asthma Control Test™ (ACT™) is a five question health survey used to measure asthma control in individuals 12 years of age and older. The survey measures the elements of asthma control as defined by the National Heart, Lung, and Blood Institute (NHLBI). ACT is an efficient, reliable, and valid method of measuring asthma control, with or without, lung functioning measures such as spirometry. Each item includes 5 response options corresponding to a 5-point Likert-type rating scale. In scoring the ACT survey, responses for each of the 5 items are summed to yield a score ranging from 5 (poor control of asthma) to 25 (complete control of asthma).

11. Measurement of Quality of Life With the AQLQ (Asthma Quality of Life Questionnaire) at Baseline [Baseline]

    The Asthma Quality of Life Questionnaire (AQLQ) was developed to measure the functional problems (physical, emotional, social and occupational) that are most troublesome to adults (17-70 years) with asthma. There are 32 questions in the AQLQ and they are in 4 domains (symptoms, activity limitation, emotional function and environmental stimuli). The activity domain contains 5 'patient-specific' questions. This allows patients to select 5 activities in which they are most limited and these activities will be assessed at each follow-up. Patients are asked to think about how they have been during the previous two weeks and to respond to each of the 32 questions on a 7-point scale (7 = not impaired at all - 1 = severely impaired). The overall AQLQ score is the mean of all 32 responses and the individual domain scores are the means of the items in those domains (http://www.qoltech.co.uk/aqlq.html).

12. Measurement of Quality of Life With the AQLQ (Asthma Quality of Life Questionnaire) at Endpoint [60 days]

    The Asthma Quality of Life Questionnaire (AQLQ) was developed to measure the functional problems (physical, emotional, social and occupational) that are most troublesome to adults (17-70 years) with asthma. There are 32 questions in the AQLQ and they are in 4 domains (symptoms, activity limitation, emotional function and environmental stimuli). The activity domain contains 5 'patient-specific' questions. This allows patients to select 5 activities in which they are most limited and these activities will be assessed at each follow-up. Patients are asked to think about how they have been during the previous two weeks and to respond to each of the 32 questions on a 7-point scale (7 = not impaired at all - 1 = severely impaired). The overall AQLQ score is the mean of all 32 responses and the individual domain scores are the means of the items in those domains (http://www.qoltech.co.uk/aqlq.html).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Outpatients (≥18 and ≤ 75 years of age) female or male

• Willingness to participate and comply with procedures by signing a written informed consent

• Moderate/severe persistent allergic rhinitis according to Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines with a history of intermittent, mild persistent or moderate persistent asthma according to GINA guidelines

• Confirmed allergy to at least one of the following allergen preparations: house dust mite f; house dust mite p; cockroach; bush mix; tree mix; grass mix; weed mix, cat; or dog.

• All prior medication washout times had been observed

• Female volunteers of childbearing potential had to agree to use a medically accepted method of contraception

• Negative urine pregnancy test

• Without a concomitant chronic medical condition (e.g., significant cardiovascular disease, diabetes requiring medication, chronic kidney disease, chronic thyroid disease, or coagulation defects)

• Willingness to adhere to the dosing and visit schedules

Exclusion Criteria:

• Pregnant or breastfeeding

• Female who was or intended to become pregnant during the study or within 12 weeks after study completion

• Taking medications prohibited during the study or had not complied with the requirements for the designated washout periods for any of the prohibited medications

• Anatomical abnormalities of the nose (turbinate hypertrophy, septal deviation, polyps)

• Acute or chronic sinusitis currently being treated with antibiotics and/or topical or oral decongestants

• Upper respiratory tract or sinus infection that required antibiotic therapy and had not had at least a 14-day wash-out period prior to the run-in period

• Patients undergoing a progressive course of immunotherapy. Subjects on a regular maintenance schedule prior to the screening visit are eligible for study inclusion; however, subject could not receive hyposensitization treatment within 24 hours prior to any study visit

• Concomitant medical problem

• In a situation or condition that could interfere with participation in the study

• Allergic or sensitivity to the study drug or its excipients

• History of inadequate adherence to treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Civil de Guadalajara "Juan I. Menchaca"	Guadalajara	Jalisco	Mexico	44340
2	Departamento de Fisiología, CUCS, UdeG	Guadalajara	Jalisco	Mexico	44348

Sponsors and Collaborators

• Centro Universitario de Ciencias de la Salud, Mexico
• National Council of Science and Technology, Mexico
• University of Guadalajara
• Hospital Civil Juan I. Menchaca

Investigators

• Principal Investigator: Fernando R. Siller Lopez, PhD, Centro Universitario de Ciencias de la Salud, Mexico

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Health Sciences Center, University of Guadalajara
• Hospital Civil de Guadalajara

Publications

• Biewenga GP, Haenen GR, Bast A. The pharmacology of the antioxidant lipoic acid. Gen Pharmacol. 1997 Sep;29(3):315-31. Review.
• Brozek JL, Bousquet J, Baena-Cagnani CE, Bonini S, Canonica GW, Casale TB, van Wijk RG, Ohta K, Zuberbier T, Schünemann HJ; Global Allergy and Asthma European Network; Grading of Recommendations Assessment, Development and Evaluation Working Group. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol. 2010 Sep;126(3):466-76. doi: 10.1016/j.jaci.2010.06.047.
• Cho YS, Lee J, Lee TH, Lee EY, Lee KU, Park JY, Moon HB. alpha-Lipoic acid inhibits airway inflammation and hyperresponsiveness in a mouse model of asthma. J Allergy Clin Immunol. 2004 Aug;114(2):429-35.
• Comhair SA, Erzurum SC. Redox control of asthma: molecular mechanisms and therapeutic opportunities. Antioxid Redox Signal. 2010 Jan;12(1):93-124. doi: 10.1089/ARS.2008.2425. Review. Erratum in: Antioxid Redox Signal. 2010 Feb;12(2):321. Ghio,Andrew [removed]; Kinnula, Vuokko [removed]; Kliment, Corrine [removed];Montuschi, Paolo [removed]; Reddy, Sekhar [removed]; White, Carl [removed].
• Juniper EF, Guyatt GH, Epstein RS, Ferrie PJ, Jaeschke R, Hiller TK. Evaluation of impairment of health related quality of life in asthma: development of a questionnaire for use in clinical trials. Thorax. 1992 Feb;47(2):76-83.
• Kroegel C. [Global Initiative for Asthma Management and Prevention--GINA 2006]. Pneumologie. 2007 May;61(5):295-304. German.
• Lee KS, Kim SR, Park SJ, Min KH, Lee KY, Jin SM, Yoo WH, Lee YC. Antioxidant down-regulates interleukin-18 expression in asthma. Mol Pharmacol. 2006 Oct;70(4):1184-93. Epub 2006 Jul 5.
• Miller AL. The etiologies, pathophysiology, and alternative/complementary treatment of asthma. Altern Med Rev. 2001 Feb;6(1):20-47. Review.
• Patel BD, Welch AA, Bingham SA, Luben RN, Day NE, Khaw KT, Lomas DA, Wareham NJ. Dietary antioxidants and asthma in adults. Thorax. 2006 May;61(5):388-93. Epub 2006 Feb 7.
• Rahman I. Oxidative stress, chromatin remodeling and gene transcription in inflammation and chronic lung diseases. J Biochem Mol Biol. 2003 Jan 31;36(1):95-109. Review.
• Riedl MA, Saxon A, Diaz-Sanchez D. Oral sulforaphane increases Phase II antioxidant enzymes in the human upper airway. Clin Immunol. 2009 Mar;130(3):244-51. doi: 10.1016/j.clim.2008.10.007. Epub 2008 Nov 22.
• Schatz M, Sorkness CA, Li JT, Marcus P, Murray JJ, Nathan RA, Kosinski M, Pendergraft TB, Jhingran P. Asthma Control Test: reliability, validity, and responsiveness in patients not previously followed by asthma specialists. J Allergy Clin Immunol. 2006 Mar;117(3):549-56.
• Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM. Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta. 2009 Oct;1790(10):1149-60. doi: 10.1016/j.bbagen.2009.07.026. Epub 2009 Aug 4. Review.
• Singh U, Jialal I. Alpha-lipoic acid supplementation and diabetes. Nutr Rev. 2008 Nov;66(11):646-57. doi: 10.1111/j.1753-4887.2008.00118.x. Review. Retraction in: Nutr Rev. 2012 Aug;70(8):482.

• Responsible Party: Fernando Siller-Lopez, Research professor, Centro Universitario de Ciencias de la Salud, Mexico
• ClinicalTrials.gov Identifier: NCT01221350
• Other Study ID Numbers: UdeG-FSL-2010; Salud-2010-C01-140590
• First Posted: Oct 15, 2010
• Last Update Posted: Nov 8, 2013
• Last Verified: Oct 1, 2013

• Keywords provided by Fernando Siller-Lopez, Research professor, Centro Universitario de Ciencias de la Salud, Mexico: Asthma; Allergic rhinitis; Respiratory disease; Allergy; Lipoic acid; Thioctic acid; Antioxidant; Oxidative stress
• Additional relevant MeSH terms: Rhinitis; Rhinitis, Allergic; Thioctic Acid

Study Results

Participant Flow

Recruitment Details	82 adult patients (>18 years) with history of mild intermittent to moderate asthma according to the Global Initiative for Asthma (GINA) guidelines were screened to participate in the study. Recruitment period: January-September 2011.
Pre-assignment Detail	55 patients were enrolled in the study prior to randomization and group assignment. From the 82 patients initially screened, 12 patients declined to participate and 15 patients did not meet the inclusion criteria.

Arm/Group Title	Lipoic Acid	Placebo
Arm/Group Description	Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Period Title: Overall Study
STARTED	28	27
Received Intervention	28	27
Analysis Population	23	24
COMPLETED	23	24
NOT COMPLETED	5	3

Baseline Characteristics

Arm/Group Title	Lipoic Acid	Placebo	Total
Arm/Group Description	Lipoic acid (ALA) 600 mg oral dose (two 300 mg capsules) once daily in the morning during 60 days	Placebo (two 300 mg capsules filled with vehicle) orally once daily in the morning during 60 days	Total of all reporting groups
Overall Participants	28	27	55
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.9 (10.5)	43.8 (16.6)	42.3 (13.6)
Sex: Female, Male (Count of Participants)
Female	16 57.1%	15 55.6%	31 56.4%
Male	12 42.9%	12 44.4%	24 43.6%
Region of Enrollment (participants) [Number]
Mexico	28 100%	27 100%	55 100%
Weight (Kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kg]	73.6 (16.1)	74.1 (15.9)	73.8 (16.0)
Body mass index (BMI) (Kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kg/m^2]	29.9 (5.4)	28.0 (5.0)	29.0 (5.2)

Outcome Measures

1. Primary Outcome

Title	Spirometric FVC Values at Baseline
Description	Measurement of spirometric predicted parameters at baseline. Forced vital capacity (FVC) is the volume of air that can forcibly be blown out after full inspiration, measured in liters.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lipoic Acid	Placebo
Arm/Group Description	Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Measure Participants	23	24
Mean (Standard Deviation) [Liters]	2.74 (0.68)	3.07 (0.76)

2. Secondary Outcome

Title	Induced Sputum of Glutathione (GSH)/Glutathione Disulfide (GSSG) Ratio at Baseline
Description	Induced sputum of GSH and GSSG levels at baseline. The ratio GSH/GSSG is considered an index of antioxidant status and reductive -SH groups. GSH and GSSG were measured by a microplate fluorescent assay.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lipoic Acid	Placebo
Arm/Group Description	Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Measure Participants	23	24
Mean (95% Confidence Interval) [ratio]	81.42	35.77

3. Secondary Outcome

Title	Induced Sputum of Glutathione (GSH)/Glutathione Disulfide (GSSG) Ratio at Endpoint
Description	Change in the induced sputum of antioxidant parameters GSH and GSSG levels after 60 days of treatment. The ratio GSH/GSSG is considered an index of antioxidant status and reductive -SH groups. GSH and GSSG were measured by a microplate fluorescent assay.
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lipoic Acid	Placebo
Arm/Group Description	Lipoic acid (ALA) 600 mg oral dose (two 300 mg capsules) once daily in the morning during 60 days	Placebo (two 300 mg capsules filled with vehicle) orally once daily in the morning during 60 days
Measure Participants	23	24
Mean (95% Confidence Interval) [ratio]	58.6	37.5

4. Secondary Outcome

Title	Induced Sputum Carbonylated Proteins at Baseline
Description	Proteins can become modified by a large number of reactions involving reactive oxygen species. Among these, carbonylation is an irreversible and unrepairable oxidative reaction. The main protein modifications originated from oxidative stress comprise direct oxidation of aminoacids with a thiol group, such as cysteine, oxidative glycation, and carbonylation. Oxidative protein carbonylation induce protein degradation in a nonspecific manner. Chemically, oxidative carbonylation preferentially occurs at proline, threonine, lysine, and arginine, presumably through a metal-catalyzed activation of hydrogen peroxide to a reactive intermediate. Carbonylation usually refers to a process that forms reactive ketones or aldehydes that can be reacted by 2,4-dinitrophenylhydrazine (DNPH) to form hydrazones. Direct oxidation of side chains of lysine, arginine, proline, and threonine residues, among other aminoacids, produces DNPH detectable protein products
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lipoic Acid	Placebo
Arm/Group Description	Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Measure Participants	23	24
Mean (Standard Deviation) [nmol/mg]	7.5 (4.37)	10.12 (10.81)

5. Primary Outcome

Title	Spirometric FVC Values at Endpoint
Description	Measurement of spirometric predicted parameters at the baseline and after 60 days of treatment: Forced vital capacity (FVC) is the volume of air that can forcibly be blown out after full inspiration, measured in liters.
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

Per protocol

Arm/Group Title	Lipoic Acid	Placebo
Arm/Group Description	Lipoic acid (ALA) 600 mg oral dose (two 300 mg capsules) once daily in the morning during 60 days	Placebo (two 300 mg capsules filled with vehicle) orally once daily in the morning during 60 days
Measure Participants	23	24
Mean (Standard Deviation) [Liters]	2.82 (0.77)	3.06 (0.71)

6. Secondary Outcome

Title	Induced Sputum Carbonylated Proteins at Endpoint
Description	Proteins can become modified by a large number of reactions involving reactive oxygen species. Among these, carbonylation is an irreversible and unrepairable oxidative reaction. The main protein modifications originated from oxidative stress comprise direct oxidation of aminoacids with a thiol group, such as cysteine, oxidative glycation, and carbonylation. Oxidative protein carbonylation induce protein degradation in a nonspecific manner. Chemically, oxidative carbonylation preferentially occurs at proline, threonine, lysine, and arginine, presumably through a metal-catalyzed activation of hydrogen peroxide to a reactive intermediate. Carbonylation usually refers to a process that forms reactive ketones or aldehydes that can be reacted by 2,4-dinitrophenylhydrazine (DNPH) to form hydrazones. Direct oxidation of side chains of lysine, arginine, proline, and threonine residues, among other aminoacids, produces DNPH detectable protein products.
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lipoic Acid	Placebo
Arm/Group Description	Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Measure Participants	23	24
Mean (Standard Deviation) [nmol/mg]	3.24 (2.2)	4.21 (2.47)

7. Primary Outcome

Title	Spirometric FEV1 Values at Baseline
Description	Measurement of spirometric predicted parameters at baseline: Forced expiratory volume in 1 second (FEV1), volume that has been exhaled at the end of the first second of forced expiration.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lipoic Acid	Placebo
Arm/Group Description	Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Measure Participants	23	24
Mean (Standard Deviation) [Liters]	2.01 (0.63)	2.37 (0.65)

8. Primary Outcome

Title	Spirometric FEV1 Values at Endpoint
Description	Measurement of spirometric predicted parameters after 60 days of treatment. Forced expiratory volume in 1 second (FEV1), volume that has been exhaled at the end of the first second of forced expiration.
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lipoic Acid	Placebo
Arm/Group Description	Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Measure Participants	23	24
Mean (Standard Deviation) [Liters]	2.26 (0.69)	2.35 (0.66)

9. Primary Outcome

Title	Spirometric FEF Values at Baseline
Description	Measurement of spirometric parameters at baseline: Forced expiratory flow (FEF) is the flow (or speed) of air coming out of the lung during the middle portion of a forced expiration.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lipoic Acid	Placebo
Arm/Group Description	Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Measure Participants	23	24
Mean (Standard Deviation) [Liters/sec]	4.89 (1.72)	6.09 (1.96)

10. Primary Outcome

Title	Spirometric FEF Values at Endpoint
Description	Measurement of spirometric FEF after 60 days of treatment: Forced expiratory flow (FEF) is the flow (or speed) of air coming out of the lung during the middle portion of a forced expiration.
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lipoic Acid	Placebo
Arm/Group Description	Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Measure Participants	23	24
Mean (Standard Deviation) [Liters/sec]	5.47 (1.53)	6.10 (1.68)

11. Secondary Outcome

Title	Induced Sputum Eosinophils at Baseline
Description	Eosinophils, a prominent feature of asthma, are found in increased numbers in the circulation and sputum, usually in relation to the severity of asthma.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lipoic Acid	Placebo
Arm/Group Description	Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Measure Participants	23	24
Measure Eosinophils content	100	300
Mean (95% Confidence Interval) [Eosinophil percentage in sputum cells]	12.88	6.10

12. Secondary Outcome

Title	Induced Sputum Eosinophils at Endpoint
Description	Eosinophils, a prominent feature of asthma, are found in increased numbers in the circulation and sputum, usually in relation to the severity of asthma.
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lipoic Acid	Placebo
Arm/Group Description	Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Measure Participants	23	24
Measure Eosinophils content	100	300
Mean (95% Confidence Interval) [Eosinophil percentage in sputum cells]	6.39	5.68

13. Secondary Outcome

Title	Inflammatory Interleukin-4 (IL-4) Sputum Levels at Baseline
Description	Inflammatory IL-4 sputum levels after 60 days of treatment. Sputum induction is a semi-invasive technique used to detect and monitor airway inflammation. IL-4 is a Th2 cytokine that promote airway inflammation in asthma. IL-4 drives the production of immunoglobulin E (IgE) in B cells. IL-4 was measured by ELISA.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lipoic Acid	Placebo
Arm/Group Description	Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Measure Participants	23	24
Mean (Standard Deviation) [pg/mL]	37.77 (38.04)	39.90 (50.03)

14. Secondary Outcome

Title	Inflammatory IL-4 Sputum Levels at Endpoint
Description	Inflammatory IL-4 sputum levels after 60 days of treatment. Sputum induction is a semi-invasive technique used to detect and monitor airway inflammation. IL-4 is a Th2 cytokine that promote airway inflammation in asthma. IL-4 drives the production of IgE in B cells. IL-4 was measured by ELISA.
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lipoic Acid	Placebo
Arm/Group Description	Lipoic acid (ALA) 600 mg oral dose (two 300 mg capsules) once daily in the morning during 60 days	Placebo (two 300 mg capsules filled with vehicle) orally once daily in the morning during 60 days
Measure Participants	23	24
Mean (Standard Deviation) [pg/mL]	14.53 (12.96)	23.19 (34.39)

15. Secondary Outcome

Title	Measurement of Quality of Life With the ACT (Asthma Control Test) at Baseline
Description	Assessment of Quality of life scores with the ACT (Asthma Control Test). The ACT is a way to determine if the asthma symptoms are well controlled. The Asthma Control Test™ (ACT™) is a five question health survey used to measure asthma control in individuals 12 years of age and older. The survey measures the elements of asthma control as defined by the National Heart, Lung, and Blood Institute (NHLBI). ACT is an efficient, reliable, and valid method of measuring asthma control, with or without, lung functioning measures such as spirometry. Each item includes 5 response options corresponding to a 5-point Likert-type rating scale. In scoring the ACT survey, responses for each of the 5 items are summed to yield a score ranging from 5 (poor control of asthma) to 25 (complete control of asthma).
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lipoic Acid	Placebo
Arm/Group Description	Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Measure Participants	23	24
Mean (Standard Deviation) [units on a scale]	13.65 (4.35)	14.46 (4.85)

16. Secondary Outcome

Title	Measurement of Quality of Life With the ACT (Asthma Control Test) at Endpoint
Description	Assessment of Quality of life scores with the ACT (Asthma Control Test). The ACT is a way to determine if the asthma symptoms are well controlled. The Asthma Control Test™ (ACT™) is a five question health survey used to measure asthma control in individuals 12 years of age and older. The survey measures the elements of asthma control as defined by the National Heart, Lung, and Blood Institute (NHLBI). ACT is an efficient, reliable, and valid method of measuring asthma control, with or without, lung functioning measures such as spirometry. Each item includes 5 response options corresponding to a 5-point Likert-type rating scale. In scoring the ACT survey, responses for each of the 5 items are summed to yield a score ranging from 5 (poor control of asthma) to 25 (complete control of asthma).
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lipoic Acid	Placebo
Arm/Group Description	Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Measure Participants	23	24
Mean (Standard Deviation) [units on a scale]	19.13 (3.62)	17.71 (4.03)

17. Secondary Outcome

Title	Measurement of Quality of Life With the AQLQ (Asthma Quality of Life Questionnaire) at Baseline
Description	The Asthma Quality of Life Questionnaire (AQLQ) was developed to measure the functional problems (physical, emotional, social and occupational) that are most troublesome to adults (17-70 years) with asthma. There are 32 questions in the AQLQ and they are in 4 domains (symptoms, activity limitation, emotional function and environmental stimuli). The activity domain contains 5 'patient-specific' questions. This allows patients to select 5 activities in which they are most limited and these activities will be assessed at each follow-up. Patients are asked to think about how they have been during the previous two weeks and to respond to each of the 32 questions on a 7-point scale (7 = not impaired at all - 1 = severely impaired). The overall AQLQ score is the mean of all 32 responses and the individual domain scores are the means of the items in those domains (http://www.qoltech.co.uk/aqlq.html).
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lipoic Acid	Placebo
Arm/Group Description	Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Measure Participants	23	24
Mean (Standard Deviation) [units on a scale]	3.86 (1.32)	3.72 (1.61)

18. Secondary Outcome

Title	Measurement of Quality of Life With the AQLQ (Asthma Quality of Life Questionnaire) at Endpoint
Description	The Asthma Quality of Life Questionnaire (AQLQ) was developed to measure the functional problems (physical, emotional, social and occupational) that are most troublesome to adults (17-70 years) with asthma. There are 32 questions in the AQLQ and they are in 4 domains (symptoms, activity limitation, emotional function and environmental stimuli). The activity domain contains 5 'patient-specific' questions. This allows patients to select 5 activities in which they are most limited and these activities will be assessed at each follow-up. Patients are asked to think about how they have been during the previous two weeks and to respond to each of the 32 questions on a 7-point scale (7 = not impaired at all - 1 = severely impaired). The overall AQLQ score is the mean of all 32 responses and the individual domain scores are the means of the items in those domains (http://www.qoltech.co.uk/aqlq.html).
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lipoic Acid	Placebo
Arm/Group Description	Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Measure Participants	23	24
Mean (Standard Deviation) [units on a scale]	5.57 (1.17)	5.10 (1.24)

Adverse Events

Time Frame	60 days
Adverse Event Reporting Description	Serious or Other (non-serious) Adverse Events were collected/assessed, but none were observed during the 60 days period of intervention.
Arm/Group Title	Lipoic Acid		Placebo
Arm/Group Description	Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning		Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
All Cause Mortality
	Lipoic Acid		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Lipoic Acid		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Lipoic Acid		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/24 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.