In the Present Study, we Investigated the Effects of Oral Ambroxol on Tear Film and Ocular Surface.Phase 1/2NCT01713179
Effects of Oral Mucolytics on Tear Film and Ocular Surface
A Phase 1/2 study testing Ambroxol hydrochloride (Mucopect®, 60 mg, Boehringer Ingelheim) in people with In the Present Study, we Investigated the Effects of Oral Ambroxol on Tear Film and Ocular Surface., run by Hallym University Kangnam Sacred Heart Hospital at 1 site in South Korea.
Trial summary
Ambroxol is a metabolite of bromhexine and possesses mucokinetic and secretolytic properties that are also found in mucolytic agents.1 Ambroxol has been used for decades for the treatment of respiratory disorders associated with excessive mucus, including chronic inflammatory pulmonary conditions, bronchitis, and… Read more about this study
- Who is it for?
- Ages 25 to 29 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- In the Present Study, we Investigated the Effects of Oral Ambroxol on Tear Film and Ocular Surface.
- What is being tested?
- Ambroxol hydrochloride (Mucopect®, 60 mg, Boehringer Ingelheim)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteSouth Korea
- Study dates
- Aug 2011to Oct 2011
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 29 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Twenty healthy male volunteers aged between 25 and 29 years
Who cannot join
- Subjects with dry eye symptoms within the previous 6 months were excluded from the study.
- Subjects have any systemic diseases such as systemic lupus, rheumatoid arthritis, Sjögren's syndrome or a history of ocular disease.
- Subjects have disorder of lid margin, nasolacrimal duct, and cornea.
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Hallym University, Kangnam Sacred Heart Hospital
Seoul, 150-950
About this study
Ambroxol is a metabolite of bromhexine and possesses mucokinetic and secretolytic properties that are also found in mucolytic agents.1 Ambroxol has been used for decades for the treatment of respiratory disorders associated with excessive mucus, including chronic inflammatory pulmonary conditions, bronchitis, and pneumonia.2,3 The drug changes the biophysical properties of secretions by degrading the mucin polymers, deoxyribonucleic acid, fibrin in airway secretions, and by generally decreasing viscosity.4 In addition, ambroxol increases cyclic nucleotide (cAMP or cGMP),5 which can theoretically increase tear secretion.6 Many systemic medications, such as antihistamines, antidepressants, diuretics, acne drugs, and certain blood pressure medicines can cause or exacerbate a dry eye.7,8 On the other hand, several topical medications, including mucolytics such as ambroxol and bromhexine, may be used to treat tear-deficient dry eyes by promoting lacrimal gland function.9 However, the effects of mucoactive agents on the tear film have not been investigated systemically, and mucoactive agents may have a disturbing effect on the tear film because they modify mucin.10,11 The tear film is composed of 3 unique layers, including the outermost lipid layer, the middle aqueous layer, and the innermost mucus layer; this structure enables it to perform many functions.12 The lipid layer acts as a barrier to prevent tear film evaporation, and the aqueous layer supplies oxygen and important nutrients to the cornea.13 The mucin layer, secreted mostly by conjunctival goblet cells, coats the corneal surface rendering it hydrophilic, and anchors the tear film to the corneal surface.14 Deficiencies in the amount of tear production or alteration in tear composition can lead to ocular surface disease.15 Although many studies have focused on aqueous-deficient dry eye syndrome,16-18 the effect of mucin layer defects on the tear film has not been thoroughly studied. Furthermore, very few reports have determined the effects of oral mucolytic agents on the tear film and ocular surfaces, although a study has reported that filamentary keratopathy was treated with debridement of filaments and application of topical mucolytic agents such as acetylcysteine eyedrops. In the present study, we investigated the effects of oral ambroxol on tear film and ocular surface.
Reference
- Malerba M, Ragnoli B. Ambroxol in the 21st century: pharmacological and clinical update. Expert Opin Drug Metab Toxicol 2008;4:1119-1129.
- Rubin BK. Mucolytics, expectorants, and mucokinetic medications. Respir Care 2007;52:859-865.
- Rogers DF. Mucoactive agents for airway mucus hypersecretory diseases. Respir Care 2007;52:1176-1193.
- Gupta PR. Ambroxol - Resurgence of an old molecule as an anti-inflammatory agent in chronic obstructive airway diseases. Lung India 2010;27:46-48.
- Anfossi G, Russo I, Massucco P, et al. Adenosine increase human platelet levels of cGMP through nitric oxide: possible role in its antiaggregating effect. Thromb Res 2002;105:71-78.
- Gilbard JP, Rossi SR, Heyda KG, et al. Stimulation of tear secretion by topical agents that increase cyclic nucleotide levels. Invest Ophthalmol Vis Sci 1990;31:1381-1388.
- Gayton JL. Etiology, prevalence, and treatment of dry eye disease. Clin Ophthalmol 2009;3:405-412.
- Terry MA. Dry eye in the elderly. Drugs Aging 2001;18:101-107.
- Calonge M. The treatment of dry eye. Surv Ophthalmol 2001;45:227-239.
- Yamada T, Takemura Y, Niisato N, et al. Action of N-acylated ambroxol derivatives on secretion of chloride ions in human airway epithelia. Biochem Biophys Res Commun 2009;380:586-590.
- Hasegawa I, Niisato N, Iwasaki Y, et al. Ambroxol-induced modification of ion transport in human airway Calu-3 epithelia. Biochem Biophys Res Commun 2006;343:475-482.
- Antti H, Tuulikki S, Matej O. Human tear fluid lipidome: from composition to function. PLoS One 2011;6:e19553.
- Ohashi Y, Dogru M, Tsubota K. Laboratory findings in tear fluid analysis. Clin Chim Acta 2006;396:17-28.
- Davidson HJ, Kuonen VJ. The tear film and ocular mucins. Vet Ophthalmol 2004;7:71-77.
- Bhavsar AS, Bhavsar SG, Jain SM. A review on recent advances in dry eye: pathogenesis and management. Oman J Ophthalmol 2011;4:50-56.
- Patel S, Farrell J, Blades KJ, et al. The value of a phenol red impregnated thread for differentiating between the aqueous and non-aqueous deficient dry eye. Ophthalmic Physiol Opt 1998;18:471-476.
- Lin H, Li W, Dong N, et al. Changes in corneal epithelial layer inflammatory cells in aqueous tear-deficient dry eye. Invest Ophthalmol Vis Sci 2010;51:122-128.
- Yokoi N, Yamada H, Mizukusa Y, et al. Rheology of tear film lipid layer spread in normal and aqueous tear-deficient dry eye. Invest Ophthalmol Vis Sci 2008;49:5319-5324.
- Conditions
- In the Present Study, we Investigated the Effects of Oral Ambroxol on Tear Film and Ocular Surface.
- Being tested
- Ambroxol hydrochloride (Mucopect®, 60 mg, Boehringer Ingelheim)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ambroxol hydrochloride (Mucopect®, 60 mg, Boehringer Ingelheim)Drug
| Study group | Role | What they receive |
|---|---|---|
| ambroxol | Experimental | Ambroxol hydrochloride (Mucopect®, trans-4[2-amino-3.5-dibrombenzylamino]-cyclohexanhydro-chloride, 60 mg, Boehringer Ingelheim) was administered orally to subjects in the ambroxol group immediately after initial examination (10 AM).
one dose for one day Receives: Drug: Ambroxol hydrochloride (Mucopect®, 60 mg, Boehringer Ingelheim) |
| control | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Visual analog pain score
Visual analog pain score Subjective discomfort or pain was graded numerically using the VAS. The scale range was 0 (absence of pain) to 10 (maximal pain). Subjects were asked to describe their symptoms using the VAS.
Measured: 1 day
Fluorescein staining
Corneal fluorescein staining was examined with a biomicroscope under blue-light illumination after fluorescein instillation into the tear film. The corneal surface was divided into 5 areas (1 center zone and 4 peripheral zones). Corneal erosion staining was recorded using a standardized grading system of 0 to 3 for each of the 5 areas.
Measured: 1 day
Tear break up time
Fluorescein was placed in the lower conjunctival sac using a fluorescein strip (HAAG-STREIT, Köniz, Switzerland), and the time between the last blink and the first appearance of a dark spot was measured using the cobalt blue light of a slit lamp. This procedure was repeated 3 times, and the average value was recorded.
Measured: 1 day
Fluorescein clearance test
After applying 1 drop of 0.5% proparacaine hydrochloride to each eye, the inferior fornix was carefully dried with tissue paper. Fluorescein was then applied to the inferior fornix of each eye. The patient continued to sit in the examination room under ambient light and was asked to blink normally. After 10 minutes had elapsed, as determined by a timer, a Schirmer paper strip was inserted into the inferior fornix of each eye at a position approximately one-third lateral to the temporal caruncle. This maneuver was repeated for 3 times over a period of 30 minutes at 10-minute intervals.
Measured: 1 day
Schirmer's test
One drop of 0.5% proparacaine hydrochloride (Alcaine, Alcon, Forth Worth, TX, USA) was instilled in the conjunctival sac for topical anesthesia. In a silent room, filter paper (Color Bar, EagleVision, Memphis, TN, USA) was placed in the inferolateral one-third of the lower lid. Care was taken to prevent the paper from contacting the cornea. After 5 minutes, the level of strip wetting (in millimeters) was measured.
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2012 (estimated)
- Study startAug 2011
- Primary completionOct 2011
- Study completionOct 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for In the Present Study, we Investigated the Effects of Oral Ambroxol on Tear Film and Ocular Surface.Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hallym University Kangnam Sacred Heart Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Young Joo Shin, Hallym University Kangnam Sacred Heart Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01713179
- Sponsor's protocol ID
- 2011-07-63
- Status last verified
- Aug 2016
- First submitted
- 22 Oct 2012
- Last updated
- 30 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Kim D, Kim HJ, Hyon JY, Wee WR, Shin YJ. Effects of oral mucolytics on tear film and ocular surface. Cornea. 2013 Jul;32(7):933-8. doi: 10.1097/ICO.0b013e318285c8d3.
PubMed 23538621
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Oral Mucolytics on Tear Film and Ocular Surface
- ClinicalTrials.gov ID
- NCT01713179
- Acronym / sponsor ID
- 2011-07-63
- Conditions
- In the Present Study, we Investigated the Effects of Oral Ambroxol on Tear Film and Ocular Surface.
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Hallym University Kangnam Sacred Heart HospitalUniversity, hospital or other
- Study start
- Aug 2011
- Primary completion
- Oct 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 24 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Ambroxol is a metabolite of bromhexine and possesses mucokinetic and secretolytic properties that are also found in mucolytic agents.1 Ambroxol has been used for decades for the treatment of respiratory disorders associated with excessive mucus, including chronic inflammatory pulmonary conditions, bronchitis, and pneumonia.2,3 The drug changes the biophysical properties of secretions by degrading the mucin polymers, deoxyribonucleic acid, fibrin in airway secretions, and by generally decreasing viscosity.4 In addition, ambroxol increases cyclic nucleotide (cAMP or cGMP),5 which can theoretically increase tear secretion.6 Many systemic medications, such as antihistamines, antidepressants, diuretics, acne drugs, and certain blood pressure medicines can cause or exacerbate a dry eye.7,8 On the other hand, several topical medications, including mucolytics such as ambroxol and bromhexine, may be used to treat tear-deficient dry eyes by promoting lacrimal gland function.9 However, the effects of mucoactive agents on the tear film have not been investigated systemically, and mucoactive agents may have a disturbing effect on the tear film because they modify mucin.10,11 The tear film is composed of 3 unique layers, including the outermost lipid layer, the middle aqueous layer, and the innermost mucus layer; this structure enables it to perform many functions.12 The lipid layer acts as a barrier to prevent tear film evaporation, and the aqueous layer supplies oxygen and important nutrients to the cornea.13 The mucin layer, secreted mostly by conjunctival goblet cells, coats the corneal surface rendering it hydrophilic, and anchors the tear film to the corneal surface.14 Deficiencies in the amount of tear production or alteration in tear composition can lead to ocular surface disease.15 Although many studies have focused on aqueous-deficient dry eye syndrome,16-18 the effect of mucin layer defects on the tear film has not been thoroughly studied. Furthermore, very few reports have determined the effects of oral mucolytic agents on the tear film and ocular surfaces, although a study has reported that filamentary keratopathy was treated with debridement of filaments and application of topical mucolytic agents such as acetylcysteine eyedrops. In the present study, we investigated the effects of oral ambroxol on tear film and ocular surface.
Reference
- Malerba M, Ragnoli B. Ambroxol in the 21st century: pharmacological and clinical update. Expert Opin Drug Metab Toxicol 2008;4:1119-1129.
- Rubin BK. Mucolytics, expectorants, and mucokinetic medications. Respir Care 2007;52:859-865.
- Rogers DF. Mucoactive agents for airway mucus hypersecretory diseases. Respir Care 2007;52:1176-1193.
- Gupta PR. Ambroxol - Resurgence of an old molecule as an anti-inflammatory agent in chronic obstructive airway diseases. Lung India 2010;27:46-48.
- Anfossi G, Russo I, Massucco P, et al. Adenosine increase human platelet levels of cGMP through nitric oxide: possible role in its antiaggregating effect. Thromb Res 2002;105:71-78.
- Gilbard JP, Rossi SR, Heyda KG, et al. Stimulation of tear secretion by topical agents that increase cyclic nucleotide levels. Invest Ophthalmol Vis Sci 1990;31:1381-1388.
- Gayton JL. Etiology, prevalence, and treatment of dry eye disease. Clin Ophthalmol 2009;3:405-412.
- Terry MA. Dry eye in the elderly. Drugs Aging 2001;18:101-107.
- Calonge M. The treatment of dry eye. Surv Ophthalmol 2001;45:227-239.
- Yamada T, Takemura Y, Niisato N, et al. Action of N-acylated ambroxol derivatives on secretion of chloride ions in human airway epithelia. Biochem Biophys Res Commun 2009;380:586-590.
- Hasegawa I, Niisato N, Iwasaki Y, et al. Ambroxol-induced modification of ion transport in human airway Calu-3 epithelia. Biochem Biophys Res Commun 2006;343:475-482.
- Antti H, Tuulikki S, Matej O. Human tear fluid lipidome: from composition to function. PLoS One 2011;6:e19553.
- Ohashi Y, Dogru M, Tsubota K. Laboratory findings in tear fluid analysis. Clin Chim Acta 2006;396:17-28.
- Davidson HJ, Kuonen VJ. The tear film and ocular mucins. Vet Ophthalmol 2004;7:71-77.
- Bhavsar AS, Bhavsar SG, Jain SM. A review on recent advances in dry eye: pathogenesis and management. Oman J Ophthalmol 2011;4:50-56.
- Patel S, Farrell J, Blades KJ, et al. The value of a phenol red impregnated thread for differentiating between the aqueous and non-aqueous deficient dry eye. Ophthalmic Physiol Opt 1998;18:471-476.
- Lin H, Li W, Dong N, et al. Changes in corneal epithelial layer inflammatory cells in aqueous tear-deficient dry eye. Invest Ophthalmol Vis Sci 2010;51:122-128.
- Yokoi N, Yamada H, Mizukusa Y, et al. Rheology of tear film lipid layer spread in normal and aqueous tear-deficient dry eye. Invest Ophthalmol Vis Sci 2008;49:5319-5324.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ambroxol | Experimental | Drug: Ambroxol hydrochloride (Mucopect®, 60 mg, Boehringer Ingelheim)Ambroxol hydrochloride (Mucopect®, trans-4[2-amino-3.5-dibrombenzylamino]-cyclohexanhydro-chloride, 60 mg, Boehringer Ingelheim) was administered orally to subjects in the ambroxol group immediately after initial examination (10 AM). one dose for one day |
| control | No intervention | – |
Who may qualify
- Ages
- 25 to 29 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Twenty healthy male volunteers aged between 25 and 29 years
Key exclusion criteria (3 listed)
- Subjects with dry eye symptoms within the previous 6 months were excluded from the study.
- Subjects have any systemic diseases such as systemic lupus, rheumatoid arthritis, Sjögren's syndrome or a history of ocular disease.
- Subjects have disorder of lid margin, nasolacrimal duct, and cornea.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ambroxol hydrochloride (Mucopect®, 60 mg, Boehringer Ingelheim) | Drug | ambroxol |
Primary outcome
Visual analog pain score
Time frame: 1 day
Visual analog pain score Subjective discomfort or pain was graded numerically using the VAS. The scale range was 0 (absence of pain) to 10 (maximal pain). Subjects were asked to describe their symptoms using the VAS.
Fluorescein staining
Time frame: 1 day
Corneal fluorescein staining was examined with a biomicroscope under blue-light illumination after fluorescein instillation into the tear film. The corneal surface was divided into 5 areas (1 center zone and 4 peripheral zones). Corneal erosion staining was recorded using a standardized grading system of 0 to 3 for each of the 5 areas.
Tear break up time
Time frame: 1 day
Fluorescein was placed in the lower conjunctival sac using a fluorescein strip (HAAG-STREIT, Köniz, Switzerland), and the time between the last blink and the first appearance of a dark spot was measured using the cobalt blue light of a slit lamp. This procedure was repeated 3 times, and the average value was recorded.
Fluorescein clearance test
Time frame: 1 day
After applying 1 drop of 0.5% proparacaine hydrochloride to each eye, the inferior fornix was carefully dried with tissue paper. Fluorescein was then applied to the inferior fornix of each eye. The patient continued to sit in the examination room under ambient light and was asked to blink normally. After 10 minutes had elapsed, as determined by a timer, a Schirmer paper strip was inserted into the inferior fornix of each eye at a position approximately one-third lateral to the temporal caruncle. This maneuver was repeated for 3 times over a period of 30 minutes at 10-minute intervals.
Schirmer's test
Time frame: 1 day
One drop of 0.5% proparacaine hydrochloride (Alcaine, Alcon, Forth Worth, TX, USA) was instilled in the conjunctival sac for topical anesthesia. In a silent room, filter paper (Color Bar, EagleVision, Memphis, TN, USA) was placed in the inferolateral one-third of the lower lid. Care was taken to prevent the paper from contacting the cornea. After 5 minutes, the level of strip wetting (in millimeters) was measured.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2016.
- Derived from this study: PubMed 23538621Kim D, Kim HJ, Hyon JY, Wee WR, Shin YJ. Effects of oral mucolytics on tear film and ocular surface. Cornea. 2013 Jul;32(7):933-8. doi: 10.1097/ICO.0b013e318285c8d3.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ambroxol hydrochloride (Mucopect®, 60 mg, Boehringer Ingelheim) in people with In the Present Study, we Investigated the Effects of Oral Ambroxol on Tear Film and Ocular Surface., run by Hallym University Kangnam Sacred Heart Hospital at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Visual analog pain score (time frame: 1 day). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01713179, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2016.