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

This study has been completed.
Sponsor:
Collaborators:
National Council of Science and Technology, Mexico
University of Guadalajara
Hospital Civil Juan I. Menchaca
Information provided by (Responsible Party):
Fernando Siller-Lopez, Centro Universitario de Ciencias de la Salud, Mexico
ClinicalTrials.gov Identifier:
NCT01221350
First received: October 14, 2010
Last updated: October 16, 2013
Last verified: October 2013
  Purpose

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 Intervention
Asthma
Allergic Rhinitis
Dietary Supplement: Lipoic acid
Dietary Supplement: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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.

Resource links provided by NLM:


Further study details as provided by Centro Universitario de Ciencias de la Salud, Mexico:

Primary Outcome Measures:
  • Spirometric FVC Values at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.

  • Spirometric FVC Values at Endpoint [ Time Frame: 60 days ] [ Designated as safety issue: No ]
    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.

  • Spirometric FEV1 Values at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.

  • Spirometric FEV1 Values at Endpoint [ Time Frame: 60 days ] [ Designated as safety issue: No ]
    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.

  • Spirometric FEF Values at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.

  • Spirometric FEF Values at Endpoint [ Time Frame: 60 days ] [ Designated as safety issue: No ]
    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:
  • Induced Sputum of Glutathione (GSH)/Glutathione Disulfide (GSSG) Ratio at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.

  • Induced Sputum of Glutathione (GSH)/Glutathione Disulfide (GSSG) Ratio at Endpoint [ Time Frame: 60 days ] [ Designated as safety issue: No ]
    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.

  • Induced Sputum Carbonylated Proteins at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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

  • Induced Sputum Carbonylated Proteins at Endpoint [ Time Frame: 60 days ] [ Designated as safety issue: No ]
    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.

  • Induced Sputum Eosinophils at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Eosinophils, a prominent feature of asthma, are found in increased numbers in the circulation and sputum, usually in relation to the severity of asthma.

  • Induced Sputum Eosinophils at Endpoint [ Time Frame: 60 days ] [ Designated as safety issue: No ]
    Eosinophils, a prominent feature of asthma, are found in increased numbers in the circulation and sputum, usually in relation to the severity of asthma.

  • Inflammatory Interleukin-4 (IL-4) Sputum Levels at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.

  • Inflammatory IL-4 Sputum Levels at Endpoint [ Time Frame: 60 days ] [ Designated as safety issue: No ]
    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.

  • Measurement of Quality of Life With the ACT (Asthma Control Test) at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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).

  • Measurement of Quality of Life With the ACT (Asthma Control Test) at Endpoint [ Time Frame: 60 days ] [ Designated as safety issue: No ]
    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).

  • Measurement of Quality of Life With the AQLQ (Asthma Quality of Life Questionnaire) at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]

    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).


  • Measurement of Quality of Life With the AQLQ (Asthma Quality of Life Questionnaire) at Endpoint [ Time Frame: 60 days ] [ Designated as safety issue: No ]

    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).



Enrollment: 55
Study Start Date: November 2010
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01221350

Locations
Mexico
Departamento de Fisiología, CUCS, UdeG
Guadalajara, Jalisco, Mexico, 44348
Hospital Civil de Guadalajara "Juan I. Menchaca"
Guadalajara, Jalisco, Mexico, 44340
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
  More Information

Additional Information:
Publications:

Responsible Party: Fernando Siller-Lopez, Research professor, Centro Universitario de Ciencias de la Salud, Mexico
ClinicalTrials.gov Identifier: NCT01221350     History of Changes
Other Study ID Numbers: UdeG-FSL-2010, Salud-2010-C01-140590
Study First Received: October 14, 2010
Results First Received: April 23, 2013
Last Updated: October 16, 2013
Health Authority: Mexico: National Council of Science and Technology
Mexico: Secretaria de Salud

Keywords provided by 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:
Asthma
Rhinitis
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Nose Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases
Thioctic Acid
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on July 22, 2014