Trial Outcomes & Findings for Effects of Lipoic Acid on Oxidative, Inflammatory and Functional Markers in Asthmatic Patients (NCT NCT01221350)

NCT ID: NCT01221350

Last Updated: 2013-11-08

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 55 participants
• Primary outcome timeframe: Baseline
• Results posted on: 2013-11-08

Participant Flow

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.

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.

Participant milestones

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

Reasons for withdrawal

Measure	Lipoic Acid Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Overall Study Discontinued intervention (GERD)	1	0
Overall Study Exclusion criteria, asthma exacerbation	0	1
Overall Study Withdrawal by Subject	4	2

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Lipoic Acid n=28 Participants Lipoic acid (ALA) 600 mg oral dose (two 300 mg capsules) once daily in the morning during 60 days	Placebo n=27 Participants Placebo (two 300 mg capsules filled with vehicle) orally once daily in the morning during 60 days	Total n=55 Participants Total of all reporting groups
Age Continuous	40.9 years STANDARD_DEVIATION 10.5 • n=5 Participants	43.8 years STANDARD_DEVIATION 16.6 • n=7 Participants	42.3 years STANDARD_DEVIATION 13.6 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	15 Participants n=7 Participants	31 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Region of Enrollment Mexico	28 participants n=5 Participants	27 participants n=7 Participants	55 participants n=5 Participants
Weight	73.6 Kg STANDARD_DEVIATION 16.1 • n=5 Participants	74.1 Kg STANDARD_DEVIATION 15.9 • n=7 Participants	73.8 Kg STANDARD_DEVIATION 16.0 • n=5 Participants
Body mass index (BMI)	29.9 Kg/m^2 STANDARD_DEVIATION 5.4 • n=5 Participants	28.0 Kg/m^2 STANDARD_DEVIATION 5.0 • n=7 Participants	29.0 Kg/m^2 STANDARD_DEVIATION 5.2 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Lipoic Acid n=23 Participants Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo n=24 Participants Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Spirometric FVC Values at Baseline	2.74 Liters Standard Deviation 0.68	3.07 Liters Standard Deviation 0.76

PRIMARY outcome

Timeframe: 60 days

Population: Per protocol

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.

Outcome measures

Measure	Lipoic Acid n=23 Participants Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo n=24 Participants Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Spirometric FVC Values at Endpoint	2.82 Liters Standard Deviation 0.77	3.06 Liters Standard Deviation 0.71

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Lipoic Acid n=23 Participants Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo n=24 Participants Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Spirometric FEV1 Values at Baseline	2.01 Liters Standard Deviation 0.63	2.37 Liters Standard Deviation 0.65

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Lipoic Acid n=23 Participants Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo n=24 Participants Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Spirometric FEV1 Values at Endpoint	2.26 Liters Standard Deviation 0.69	2.35 Liters Standard Deviation 0.66

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Lipoic Acid n=23 Participants Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo n=24 Participants Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Spirometric FEF Values at Baseline	4.89 Liters/sec Standard Deviation 1.72	6.09 Liters/sec Standard Deviation 1.96

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Lipoic Acid n=23 Participants Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo n=24 Participants Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Spirometric FEF Values at Endpoint	5.47 Liters/sec Standard Deviation 1.53	6.10 Liters/sec Standard Deviation 1.68

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Lipoic Acid n=23 Participants Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo n=24 Participants Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Induced Sputum of Glutathione (GSH)/Glutathione Disulfide (GSSG) Ratio at Baseline	81.42 ratio Interval 65.31 to 97.52	35.77 ratio Interval 11.57 to 39.9

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Lipoic Acid n=23 Participants Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo n=24 Participants Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Induced Sputum of Glutathione (GSH)/Glutathione Disulfide (GSSG) Ratio at Endpoint	58.6 ratio Interval 29.9 to 77.2	37.5 ratio Interval 13.4 to 55.9

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Lipoic Acid n=23 Participants Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo n=24 Participants Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Induced Sputum Carbonylated Proteins at Baseline	7.5 nmol/mg Standard Deviation 4.37	10.12 nmol/mg Standard Deviation 10.81

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Lipoic Acid n=23 Participants Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo n=24 Participants Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Induced Sputum Carbonylated Proteins at Endpoint	3.24 nmol/mg Standard Deviation 2.2	4.21 nmol/mg Standard Deviation 2.47

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Lipoic Acid n=100 Eosinophils content Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo n=300 Eosinophils content Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Induced Sputum Eosinophils at Baseline	12.88 Eosinophil percentage in sputum cells Interval 2.5 to 13.3	6.10 Eosinophil percentage in sputum cells Interval 1.85 to 8.25

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Lipoic Acid n=100 Eosinophils content Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo n=300 Eosinophils content Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Induced Sputum Eosinophils at Endpoint	6.39 Eosinophil percentage in sputum cells Interval 0.8 to 7.0	5.68 Eosinophil percentage in sputum cells Interval 0.8 to 7.9

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Lipoic Acid n=23 Participants Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo n=24 Participants Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Inflammatory Interleukin-4 (IL-4) Sputum Levels at Baseline	37.77 pg/mL Standard Deviation 38.04	39.90 pg/mL Standard Deviation 50.03

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Lipoic Acid n=23 Participants Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo n=24 Participants Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Inflammatory IL-4 Sputum Levels at Endpoint	14.53 pg/mL Standard Deviation 12.96	23.19 pg/mL Standard Deviation 34.39

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Lipoic Acid n=23 Participants Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo n=24 Participants Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Measurement of Quality of Life With the ACT (Asthma Control Test) at Baseline	13.65 units on a scale Standard Deviation 4.35	14.46 units on a scale Standard Deviation 4.85

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Lipoic Acid n=23 Participants Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo n=24 Participants Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Measurement of Quality of Life With the ACT (Asthma Control Test) at Endpoint	19.13 units on a scale Standard Deviation 3.62	17.71 units on a scale Standard Deviation 4.03

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Lipoic Acid n=23 Participants Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo n=24 Participants Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Measurement of Quality of Life With the AQLQ (Asthma Quality of Life Questionnaire) at Baseline	3.86 units on a scale Standard Deviation 1.32	3.72 units on a scale Standard Deviation 1.61

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Lipoic Acid n=23 Participants Lipoic acid 600 mg dose (two 300 mg capsules, p.o) once daily in the morning	Placebo n=24 Participants Placebo 600 mg vehicle (two 300 mg capsules, p.o) once daily in the morning
Measurement of Quality of Life With the AQLQ (Asthma Quality of Life Questionnaire) at Endpoint	5.57 units on a scale Standard Deviation 1.17	5.10 units on a scale Standard Deviation 1.24

Adverse Events

Lipoic Acid

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Fernando R Siller Lopez, Ph.D.

Centro Universitario de Ciencias de la Salud, Mexico

Phone: 523310585200

Email: fsiller@cucs.udg.mx

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place