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

NCT ID: NCT01221350

Last Updated: 2013-11-08

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

55 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-11-30

Study Completion Date

2012-08-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Asthma Allergic Rhinitis

Keywords

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Asthma Allergic rhinitis Respiratory disease Allergy Lipoic acid Thioctic acid Antioxidant Oxidative stress

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Lipoic acid

Lipoic acid 600 mg oral dose (two 300 mg capsules) once daily in the morning during 60 days

Group Type EXPERIMENTAL

Lipoic acid

Intervention Type DIETARY_SUPPLEMENT

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.

Placebo

Placebo (two placebo capsules) orally once daily in the morning during 60 days

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DIETARY_SUPPLEMENT

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

Interventions

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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.

Intervention Type 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

Intervention Type DIETARY_SUPPLEMENT

Other Intervention Names

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Thioctic Acid Alpha-Lipoic Acid Placebos Placebo effect

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Council of Science and Technology, Mexico

OTHER

Sponsor Role collaborator

University of Guadalajara

OTHER

Sponsor Role collaborator

Hospital Civil Juan I. Menchaca

OTHER

Sponsor Role collaborator

Centro Universitario de Ciencias de la Salud, Mexico

OTHER

Sponsor Role lead

Responsible Party

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Fernando Siller-Lopez

Research professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Fernando R. Siller Lopez, PhD

Role: PRINCIPAL_INVESTIGATOR

Centro Universitario de Ciencias de la Salud, Mexico

Locations

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Hospital Civil de Guadalajara "Juan I. Menchaca"

Guadalajara, Jalisco, Mexico

Site Status

Departamento de Fisiología, CUCS, UdeG

Guadalajara, Jalisco, Mexico

Site Status

Countries

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Mexico

References

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Kroegel C. [Global Initiative for Asthma Management and Prevention--GINA 2006]. Pneumologie. 2007 May;61(5):295-304. doi: 10.1055/s-2007-959180. German.

Reference Type BACKGROUND
PMID: 17523070 (View on PubMed)

Brozek JL, Bousquet J, Baena-Cagnani CE, Bonini S, Canonica GW, Casale TB, van Wijk RG, Ohta K, Zuberbier T, Schunemann 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.

Reference Type BACKGROUND
PMID: 20816182 (View on PubMed)

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. doi: 10.1016/j.jaci.2004.04.004.

Reference Type BACKGROUND
PMID: 15316528 (View on PubMed)

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. doi: 10.1124/mol.106.024737. Epub 2006 Jul 5.

Reference Type BACKGROUND
PMID: 16822930 (View on PubMed)

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. doi: 10.1136/thx.2004.024935. Epub 2006 Feb 7.

Reference Type BACKGROUND
PMID: 16467075 (View on PubMed)

Miller AL. The etiologies, pathophysiology, and alternative/complementary treatment of asthma. Altern Med Rev. 2001 Feb;6(1):20-47.

Reference Type BACKGROUND
PMID: 11207455 (View on PubMed)

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. doi: 10.5483/bmbrep.2003.36.1.095.

Reference Type BACKGROUND
PMID: 12542980 (View on PubMed)

Biewenga GP, Haenen GR, Bast A. The pharmacology of the antioxidant lipoic acid. Gen Pharmacol. 1997 Sep;29(3):315-31. doi: 10.1016/s0306-3623(96)00474-0.

Reference Type BACKGROUND
PMID: 9378235 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19019027 (View on PubMed)

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. doi: 10.1136/thx.47.2.76.

Reference Type BACKGROUND
PMID: 1549827 (View on PubMed)

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. doi: 10.1016/j.jaci.2006.01.011.

Reference Type BACKGROUND
PMID: 16522452 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19028145 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19634987 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19664690 (View on PubMed)

Related Links

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http://www.cucs.udg.mx

Health Sciences Center, University of Guadalajara

http://www.hcg.udg.mx/

Hospital Civil de Guadalajara

Other Identifiers

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Salud-2010-C01-140590

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

UdeG-FSL-2010

Identifier Type: -

Identifier Source: org_study_id